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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Mini-Review Article

Structural Insight on GPR119 Agonist as Potential Therapy for Type II Diabetes: A Comprehensive Review

Author(s): Priyanshu Nema, Vivek Asati, Priyadarshi Kendya, Twinkle Gupta, Shivangi Agarwal, Shivam Kori, Varsha Kashaw, Arun K. Iyer and Sushil Kumar Kashaw*

Volume 23, Issue 21, 2023

Published on: 10 April, 2023

Page: [2008 - 2040] Pages: 33

DOI: 10.2174/1389557523666230302140658

Price: $65

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Abstract

Diabetes Mellitus (DM) is a long-term metabolic condition that is characterized by excessive blood glucose. DM is the third most death-causing disease, leading to retinopathy, nephropathy, loss of vision, stroke, and cardiac arrest. Around 90% of the total cases of diabetic patients have Type II Diabetes Mellitus (T2DM). Among various approaches for the treatment of T2DM. G proteincoupled receptors (GPCRs) 119 have been identified as a new pharmacological target. GPR119 is distributed preferentially in the pancreas β-cells and gastrointestinal tract (enteroendocrine cells) in humans. GPR119 receptor activation elevates the release of incretin hormones such as Glucagon-Like Peptide (GLP1) and Glucose Dependent Insulinotropic Polypeptide (GIP) from intestinal K and L cells. GPR119 receptor agonists stimulate intracellular cAMP production via Gαs coupling to adenylate cyclase. GPR119 has been linked to the control of insulin release by pancreatic β-cells, as well as the generation of GLP-1 by enteroendocrine cells in the gut, as per in vitro assays. The dual role of the GPR119 receptor agonist in the treatment of T2DM leads to the development of a novel prospective anti-diabetic drug and is thought to have decreased the probability of inducing hypoglycemia. GPR119 receptor agonists exert their effects in one of two ways: either by promoting glucose absorption by β-cells, or by inhibiting α-cells' ability to produce glucose. In this review, we summarized potential targets for the treatment of T2DM with special reference to GPR119 along with its pharmacological effects, several endogenous as well as exogenous agonists, and its pyrimidine nucleus containing synthetic ligands.

Graphical Abstract

[1]
Manaithiya, A.; Alam, O.; Sharma, V.; Javed Naim, M.; Mittal, S.; Khan, I.A. GPR119 Agonists: Novel Therapeutic Agents for Type 2 Diabetes Mellitus. In: Bioorganic Chemistry; Elsevier Inc.: Amsterdam, 2021, p. 113.
[2]
Center for Disease Control and Prevention. What is Diabetes? Available from: https://www.cdc.gov/diabetes/basics/diabetes.html
[3]
Goodman, L.S.; Brunton, L.L.; Chabner, B.; Knollmann, B.C. Goodman & Gilman’s pharmacological basis of therapeutics; McGraw-Hill: New York, 2011.
[4]
Chatterjee, S.; Khunti, K.; Davies, M.J. Type 2 diabetes. Lancet, 2017, 389(10085), 2239-2251.
[http://dx.doi.org/10.1016/S0140-6736(17)30058-2] [PMID: 28190580]
[5]
Foye, W.O.; Lemke, T.L.; Williams, D.A. Foye`s Principles of Medicinal Chemistry;Wolters Kluwer Health/Lippincott Williams & Wilkins:Philadephia, 2013.
[6]
Tripathi, K.D. Essentials of Medical Pharmacology, 7th Ed.; Jaypee Brothers Medical Publishers (P) Ltd.: New Delhi, 2013.
[7]
Thrower, S.L.; Bingley, P.J. What is type 1 diabetes? Medicine, 2010, 38(11), 592-596.
[http://dx.doi.org/10.1016/j.mpmed.2010.08.003] [PMID: 20061432]
[8]
Dowarah, J.; Singh, V.P. Anti-diabetic drugs recent approaches and advancements. Bioorg. Med. Chem., 2020, 28(5), 115263.
[http://dx.doi.org/10.1016/j.bmc.2019.115263] [PMID: 32008883]
[9]
Leslie, R.D. Predicting adult-onset autoimmune diabetes: Clarity from complexity. Diabetes, 2010, 59(2), 330-331.
[http://dx.doi.org/10.2337/db09-1620] [PMID: 20103711]
[10]
Rother, K.I. Diabetes treatment--bridging the divide. N. Engl. J. Med., 2007, 356(15), 1499-1501.
[http://dx.doi.org/10.1056/NEJMp078030] [PMID: 17429082]
[11]
Todd, J.A. Etiology of type 1 diabetes. Immunity, 2010, 32(4), 457-467.
[http://dx.doi.org/10.1016/j.immuni.2010.04.001] [PMID: 20412756]
[12]
Bluestone, J.A.; Herold, K.; Eisenbarth, G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature, 2010, 464(7293), 1293-1300.
[http://dx.doi.org/10.1038/nature08933] [PMID: 20432533]
[13]
Wild, S.; Roglic, G.; Green, A.; Sicree, R.; King, H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care, 2004, 27(5), 1047-1053.
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[14]
Reddy, S.S.K. Diagnosis of Diabetes Mellitus in Older Adults. Clin. Geriatr. Med., 2020, 36(3), 379-384.
[http://dx.doi.org/10.1016/j.cger.2020.04.011] [PMID: 32586468]
[15]
Gökçay Canpolat, A.; Şahin, M. Glucose lowering treatment modalities of type 2 Diabetes Mellitus. Adv. Exp. Med. Biol., 2020, 1307, 7-27.
[http://dx.doi.org/10.1007/5584_2020_516] [PMID: 32200500]
[16]
Li, Q.; Deng, X.; Jiang, N.; Meng, L.; Xing, J.; Jiang, W.; Xu, Y. Identification and structure–activity relationship exploration of uracil-based benzoic acid and ester derivatives as novel dipeptidyl Peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus. Eur. J. Med. Chem., 2021, 225, 113765.
[http://dx.doi.org/10.1016/j.ejmech.2021.113765] [PMID: 34399391]
[17]
Hu, C.; Jia, W. Therapeutic medications against diabetes: What we have and what we expect. Adv. Drug Deliv. Rev., 2019, 139, 3-15.
[http://dx.doi.org/10.1016/j.addr.2018.11.008] [PMID: 30529309]
[18]
Hussain, H.; Abbas, G.; Green, I.R.; Ali, I. Dipeptidyl peptidase IV inhibitors as a potential target for diabetes: Patent review (2015-2018). Expert Opin. Ther. Pat., 2019, 29(7), 535-553.
[http://dx.doi.org/10.1080/13543776.2019.1632290] [PMID: 31203700]
[19]
Suzuki, R.; Brown, G.A.; Christopher, J.A.; Scully, C.C.G.; Congreve, M. Recent developments in therapeutic peptides for the glucagon-like peptide 1 and 2 Receptors. J. Med. Chem., 2020, 63(3), 905-927.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00835] [PMID: 31577440]
[20]
Jesus, A.R.; Vila-Viçosa, D.; Machuqueiro, M.; Marques, A.P.; Dore, T.M.; Rauter, A.P. Targeting type 2 diabetes with c-glucosyl dihydrochalcones as selective sodium glucose co-transporter 2 (sglt2) inhibitors: Synthesis and biological evaluation. J. Med. Chem., 2017, 60(2), 568-579.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01134] [PMID: 28098449]
[21]
Jain, S.; Saraf, S. Type 2 diabetes mellitus-Its global prevalence and therapeutic strategies. Diabetes Metab. Syndr., 2010, 4(1), 48-56.
[http://dx.doi.org/10.1016/j.dsx.2008.04.011]
[22]
Galicia-Garcia, U.; Benito-Vicente, A.; Jebari, S.; Larrea-Sebal, A.; Siddiqi, H.; Uribe, K.B.; Ostolaza, H.; Martín, C. Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci., 2020, 21(17), 6275.
[http://dx.doi.org/10.3390/ijms21176275] [PMID: 32872570]
[23]
Rank, F.; Nn, J.O.A.; Anson, E.M. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N. Engl. J. Med., 2001, 345(11), 790-797.
[http://dx.doi.org/10.1056/NEJMoa010492] [PMID: 11556298]
[24]
Schellenberg, E.S.; Dryden, D.M.; Vandermeer, B.; Ha, C.; Korownyk, C. Lifestyle interventions for patients with and at risk for type 2 diabetes. Ann. Intern. Med., 2013, 159(8), 543-551.
[http://dx.doi.org/10.7326/0003-4819-159-8-201310150-00007] [PMID: 24126648]
[25]
Chan, J.C.; Cheung, C.K.; Swaminathan, R.; Nicholls, M.G.; Cockram, C.S. Obesity, albuminuria and hypertension among Hong Kong Chinese with non-insulin-dependent diabetes mellitus (NIDDM). Postgrad. Med. J., 1993, 69(809), 204-210.
[http://dx.doi.org/10.1136/pgmj.69.809.204] [PMID: 8497435]
[26]
McKeigue, P.M.; Shah, B.; Marmot, M.G. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascu-lar risk in South Asians. Lancet, 1991, 337(8738), 382-386.
[http://dx.doi.org/10.1016/0140-6736(91)91164-P] [PMID: 1671422]
[27]
Liu, L.L.; Yi, J.P.; Beyer, J.; Mayer-Davis, E.J.; Dolan, L.M.; Dabelea, D.M.; Lawrence, J.M.; Rodriguez, B.L.; Marcovina, S.M.; Waitzfel-der, B.E.; Fujimoto, W.Y. Type 1 and type 2 diabetes in Asian and Pacific Islander U.S. youth. Diabetes Care, 2009, 32(Suppl. 2), S133-S140.
[http://dx.doi.org/10.2337/dc09-S205] [PMID: 19246578]
[28]
Sattar, N.; Gill, J.M.R. Type 2 diabetes in migrant south Asians: Mechanisms, mitigation, and management. Lancet Diabetes Endocrinol., 2015, 3(12), 1004-1016.
[http://dx.doi.org/10.1016/S2213-8587(15)00326-5] [PMID: 26489808]
[29]
Fuchsberger, C.; Flannick, J.; Teslovich, T.M.; Mahajan, A.; Agarwala, V.; Gaulton, K.J.; Ma, C.; Fontanillas, P.; Moutsianas, L.; McCarthy, D.J.; Rivas, M.A.; Perry, J.R.B.; Sim, X.; Blackwell, T.W.; Robertson, N.R.; Rayner, N.W.; Cingolani, P.; Locke, A.E.; Tajes, J.F.; Highland, H.M.; Dupuis, J.; Chines, P.S.; Lindgren, C.M.; Hartl, C.; Jackson, A.U.; Chen, H.; Huyghe, J.R.; van de Bunt, M.; Pearson, R.D.; Kumar, A.; Müller-Nurasyid, M.; Grarup, N.; Stringham, H.M.; Gamazon, E.R.; Lee, J.; Chen, Y.; Scott, R.A.; Below, J.E.; Chen, P.; Huang, J.; Go, M.J.; Stitzel, M.L.; Pasko, D.; Parker, S.C.J.; Varga, T.V.; Green, T.; Beer, N.L.; Day-Williams, A.G.; Ferreira, T.; Fingerlin, T.; Horikoshi, M.; Hu, C.; Huh, I.; Ikram, M.K.; Kim, B.J.; Kim, Y.; Kim, Y.J.; Kwon, M.S.; Lee, J.; Lee, S.; Lin, K.H.; Maxwell, T.J.; Na-gai, Y.; Wang, X.; Welch, R.P.; Yoon, J.; Zhang, W.; Barzilai, N.; Voight, B.F.; Han, B.G.; Jenkinson, C.P.; Kuulasmaa, T.; Kuusisto, J.; Manning, A.; Ng, M.C.Y.; Palmer, N.D.; Balkau, B.; Stančáková, A.; Abboud, H.E.; Boeing, H.; Giedraitis, V.; Prabhakaran, D.; Gottes-man, O.; Scott, J.; Carey, J.; Kwan, P.; Grant, G.; Smith, J.D.; Neale, B.M.; Purcell, S.; Butterworth, A.S.; Howson, J.M.M.; Lee, H.M.; Lu, Y.; Kwak, S.H.; Zhao, W.; Danesh, J.; Lam, V.K.L.; Park, K.S.; Saleheen, D.; So, W.Y.; Tam, C.H.T.; Afzal, U.; Aguilar, D.; Arya, R.; Aung, T.; Chan, E.; Navarro, C.; Cheng, C.Y.; Palli, D.; Correa, A.; Curran, J.E.; Rybin, D.; Farook, V.S.; Fowler, S.P.; Freedman, B.I.; Griswold, M.; Hale, D.E.; Hicks, P.J.; Khor, C.C.; Kumar, S.; Lehne, B.; Thuillier, D.; Lim, W.Y.; Liu, J.; van der Schouw, Y.T.; Loh, M.; Musani, S.K.; Puppala, S.; Scott, W.R.; Yengo, L.; Tan, S.T.; Taylor, H.A., Jr; Thameem, F.; Wilson, G., Sr; Wong, T.Y.; Njølstad, P.R.; Levy, J.C.; Mangino, M.; Bonnycastle, L.L.; Schwarzmayr, T.; Fadista, J.; Surdulescu, G.L.; Herder, C.; Groves, C.J.; Wieland, T.; Bork-Jensen, J.; Brandslund, I.; Christensen, C.; Koistinen, H.A.; Doney, A.S.F.; Kinnunen, L.; Esko, T.; Farmer, A.J.; Hakaste, L.; Hodgkiss, D.; Kravic, J.; Lyssenko, V.; Hollensted, M.; Jørgensen, M.E.; Jørgensen, T.; Ladenvall, C.; Justesen, J.M.; Käräjämäki, A.; Kriebel, J.; Rathmann, W.; Lannfelt, L.; Lauritzen, T.; Narisu, N.; Linneberg, A.; Melander, O.; Milani, L.; Neville, M.; Orho-Melander, M.; Qi, L.; Qi, Q.; Roden, M.; Rolandsson, O.; Swift, A.; Rosengren, A.H.; Stirrups, K.; Wood, A.R.; Mihailov, E.; Blancher, C.; Carneiro, M.O.; Maguire, J.; Poplin, R.; Shakir, K.; Fennell, T.; DePristo, M.; Hrabé de Angelis, M.; Deloukas, P.; Gjesing, A.P.; Jun, G.; Nilsson, P.; Murphy, J.; Onofrio, R.; Thorand, B.; Hansen, T.; Meisinger, C.; Hu, F.B.; Isomaa, B.; Karpe, F.; Liang, L.; Peters, A.; Huth, C.; O’Rahilly, S.P.; Pal-mer, C.N.A.; Pedersen, O.; Rauramaa, R.; Tuomilehto, J.; Salomaa, V.; Watanabe, R.M.; Syvänen, A.C.; Bergman, R.N.; Bharadwaj, D.; Bottinger, E.P.; Cho, Y.S.; Chandak, G.R.; Chan, J.C.N.; Chia, K.S.; Daly, M.J.; Ebrahim, S.B.; Langenberg, C.; Elliott, P.; Jablonski, K.A.; Lehman, D.M.; Jia, W.; Ma, R.C.W.; Pollin, T.I.; Sandhu, M.; Tandon, N.; Froguel, P.; Barroso, I.; Teo, Y.Y.; Zeggini, E.; Loos, R.J.F.; Small, K.S.; Ried, J.S.; DeFronzo, R.A.; Grallert, H.; Glaser, B.; Metspalu, A.; Wareham, N.J.; Walker, M.; Banks, E.; Gieger, C.; Ingelsson, E. Im, H.K.; Illig, T.; Franks, P.W.; Buck, G.; Trakalo, J.; Buck, D.; Prokopenko, I.; Mägi, R.; Lind, L.; Farjoun, Y.; Owen, K.R.; Gloyn, A.L.; Strauch, K.; Tuomi, T.; Kooner, J.S.; Lee, J.Y.; Park, T.; Donnelly, P.; Morris, A.D.; Hattersley, A.T.; Bowden, D.W.; Collins, F.S.; Atzmon, G.; Chambers, J.C.; Spector, T.D.; Laakso, M.; Strom, T.M.; Bell, G.I.; Blangero, J.; Duggirala, R.; Tai, E.S.; McVean, G.; Hanis, C.L.; Wilson, J.G.; Seielstad, M.; Frayling, T.M.; Meigs, J.B.; Cox, N.J.; Sladek, R.; Lander, E.S.; Gabriel, S.; Burtt, N.P.; Mohlke, K.L.; Meitinger, T.; Groop, L.; Abecasis, G.; Florez, J.C.; Scott, L.J.; Morris, A.P.; Kang, H.M.; Boehnke, M.; Altshuler, D.; McCarthy, M.I. The genetic architecture of type 2 diabetes. Nature, 2016, 536(7614), 41-47.
[http://dx.doi.org/10.1038/nature18642] [PMID: 27398621]
[30]
McCarthy, M.I. Genomics, type 2 diabetes, and obesity. N. Engl. J. Med., 2010, 363(24), 2339-2350.
[http://dx.doi.org/10.1056/NEJMra0906948] [PMID: 21142536]
[31]
Bellou, Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses. PLoS One, 2018, 13(3), 1-27.
[32]
Hillier, T.A.; Pedula, K.L. Complications in young Adults with early-onset type 2 diabetes: Losing the relative protection of youth. Diabetes Care, 2003, 26(11), 2999-3005.
[http://dx.doi.org/10.2337/diacare.26.11.2999]
[33]
Weinstein, A.R.; Sesso, H.D.; Lee, I.M.; Cook, N.R.; Manson, J.E.; Buring, J.E.; Gaziano, J.M. Relationship of physical activity vs body mass index with type 2 diabetes in women. JAMA, 2004, 292(10), 1188-1194.
[http://dx.doi.org/10.1001/jama.292.10.1188] [PMID: 15353531]
[34]
Fu, Z.; Gilbert, E.R.; Liu, D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr. Diabetes Rev., 2013, 9(1), 25-53.
[http://dx.doi.org/10.2174/157339913804143225] [PMID: 22974359]
[35]
Halban, P.A. Proinsulin processing in the regulated and the constitutive secretory pathway. Diabetologia, 1994, 37(S2), S65-S72.
[http://dx.doi.org/10.1007/BF00400828] [PMID: 7821742]
[36]
Henry, W.L. Perspectives in diabetes. J. Natl. Med. Assoc., 1962, 54(4), 476-478.
[PMID: 13906557]
[37]
Halban, P.A.; Polonsky, K.S.; Bowden, D.W.; Hawkins, M.A.; Ling, C.; Mather, K.J.; Powers, A.C.; Rhodes, C.J.; Sussel, L.; Weir, G.C. β-cell failure in type 2 diabetes: Postulated mechanisms and prospects for prevention and treatment. Diabetes Care, 2014, 37(6), 1751-1758.
[http://dx.doi.org/10.2337/dc14-0396] [PMID: 24812433]
[38]
Moneva, M.H.; Dagogo-Jack, S. Multiple drug targets in the management of type 2 diabetes. Curr. Drug Targets, 2002, 3(3), 203-221.
[http://dx.doi.org/10.2174/1389450023347803] [PMID: 12041735]
[39]
Weir, G.C.; Laybutt, D.R.; Kaneto, H.; Bonner-Weir, S.; Sharma, A. Beta-cell adaptation and decompensation during the progression of diabetes. Diabetes, 2001, 50(2)(Suppl. 1), S154-S159.
[http://dx.doi.org/10.2337/diabetes.50.2007.S154] [PMID: 11272180]
[40]
Kim, M.K.; Cheong, Y.H.; Lee, S.H.; Kim, T.H.; Jung, I.H.; Chae, Y.; Lee, J.H.; Yang, E.K.; Park, H.; Yang, J.S.; Hong, K.W. A novel GPR119 agonist DA-1241 preserves pancreatic function via the suppression of ER stress and increased PDX1 expression. Biomed. Pharmacother., 2021, 144(10), 112324.
[http://dx.doi.org/10.1016/j.biopha.2021.112324] [PMID: 34678732]
[41]
Yamamoto, W.R.; Bone, R.N.; Sohn, P.; Syed, F.; Reissaus, C.A.; Mosley, A.L.; Wijeratne, A.B.; True, J.D.; Tong, X.; Kono, T.; Evans-Molina, C. Endoplasmic reticulum stress alters ryanodine receptor function in the murine pancreatic β cell. J. Biol. Chem., 2019, 294(1), 168-181.
[http://dx.doi.org/10.1074/jbc.RA118.005683] [PMID: 30420428]
[42]
Liu, M.; Weiss, M.A.; Arunagiri, A.; Yong, J.; Rege, N.; Sun, J.; Haataja, L.; Kaufman, R.J.; Arvan, P. Biosynthesis, structure, and folding of the insulin precursor protein. Diabetes Obes. Metab., 2018, 20(Suppl. 2), 28-50.
[http://dx.doi.org/10.1111/dom.13378] [PMID: 30230185]
[43]
Höppener, J.W.; Ahrén, B.; and Lips, C.J. 2000, Islet amyloid and type 2 diabetes mellitus. New England J. Med., 343(6), 411-419.
[http://dx.doi.org/10.1056/nejm200008103430607]
[44]
Westermark, P. Amyloid and polypeptide hormones: What is their interrelationship? Amyloid, 1994, 1(1), 47-60.
[http://dx.doi.org/10.3109/13506129409148624]
[45]
Flannick, J.; Thorleifsson, G.; Beer, N.L.; Jacobs, S.B.R.; Grarup, N.; Burtt, N.P.; Mahajan, A.; Fuchsberger, C.; Atzmon, G.; Benedikts-son, R.; Blangero, J.; Bowden, D.W.; Brandslund, I.; Brosnan, J.; Burslem, F.; Chambers, J.; Cho, Y.S.; Christensen, C.; Douglas, D.A.; Duggirala, R.; Dymek, Z.; Farjoun, Y.; Fennell, T.; Fontanillas, P.; Forsén, T.; Gabriel, S.; Glaser, B.; Gudbjartsson, D.F.; Hanis, C.; Han-sen, T.; Hreidarsson, A.B.; Hveem, K.; Ingelsson, E.; Isomaa, B.; Johansson, S.; Jørgensen, T.; Jørgensen, M.E.; Kathiresan, S.; Kong, A.; Kooner, J.; Kravic, J.; Laakso, M.; Lee, J.Y.; Lind, L.; Lindgren, C.M.; Linneberg, A.; Masson, G.; Meitinger, T.; Mohlke, K.L.; Molven, A.; Morris, A.P.; Potluri, S.; Rauramaa, R.; Ribel-Madsen, R.; Richard, A.M.; Rolph, T.; Salomaa, V.; Segrè, A.V.; Skärstrand, H.; Steint-horsdottir, V.; Stringham, H.M.; Sulem, P.; Tai, E.S.; Teo, Y.Y.; Teslovich, T.; Thorsteinsdottir, U.; Trimmer, J.K.; Tuomi, T.; Tuomileh-to, J.; Vaziri-Sani, F.; Voight, B.F.; Wilson, J.G.; Boehnke, M.; McCarthy, M.I.; Njølstad, P.R.; Pedersen, O.; Groop, L.; Cox, D.R.; Ste-fansson, K.; Altshuler, D. Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat. Genet., 2014, 46(4), 357-363.
[http://dx.doi.org/10.1038/ng.2915] [PMID: 24584071]
[46]
del Bosque-Plata, L.; Martínez-Martínez, E.; Espinoza-Camacho, M.Á.; Gragnoli, C. The role of TCF7L2 in type 2 diabetes. Diabetes, 2021, 70(6), 1220-1228.
[http://dx.doi.org/10.2337/db20-0573] [PMID: 34016596]
[47]
Lyssenko, V.; Nagorny, C.L.F.; Erdos, M.R.; Wierup, N.; Jonsson, A.; Spégel, P.; Bugliani, M.; Saxena, R.; Fex, M.; Pulizzi, N.; Isomaa, B.; Tuomi, T.; Nilsson, P.; Kuusisto, J.; Tuomilehto, J.; Boehnke, M.; Altshuler, D.; Sundler, F.; Eriksson, J.G.; Jackson, A.U.; Laakso, M.; Marchetti, P.; Watanabe, R.M.; Mulder, H.; Groop, L. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat. Genet., 2009, 41(1), 82-88.
[http://dx.doi.org/10.1038/ng.288] [PMID: 19060908]
[48]
Steinthorsdottir, V.; Thorleifsson, G.; Reynisdottir, I.; Benediktsson, R.; Jonsdottir, T.; Walters, G.B.; Styrkarsdottir, U.; Gretarsdottir, S.; Emilsson, V.; Ghosh, S.; Baker, A.; Snorradottir, S.; Bjarnason, H.; Ng, M.C.Y.; Hansen, T.; Bagger, Y.; Wilensky, R.L.; Reilly, M.P.; Adeyemo, A.; Chen, Y.; Zhou, J.; Gudnason, V.; Chen, G.; Huang, H.; Lashley, K.; Doumatey, A.; So, W.Y.; Ma, R.C.Y.; Andersen, G.; Borch-Johnsen, K.; Jorgensen, T.; van Vliet-Ostaptchouk, J.V.; Hofker, M.H.; Wijmenga, C.; Christiansen, C.; Rader, D.J.; Rotimi, C.; Gurney, M.; Chan, J.C.N.; Pedersen, O.; Sigurdsson, G.; Gulcher, J.R.; Thorsteinsdottir, U.; Kong, A.; Stefansson, K. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat. Genet., 2007, 39(6), 770-775.
[http://dx.doi.org/10.1038/ng2043] [PMID: 17460697]
[49]
Voight, B.F.; Scott, L.J.; Steinthorsdottir, V.; Morris, A.P.; Dina, C.; Welch, R.P.; Zeggini, E.; Huth, C.; Aulchenko, Y.S.; Thorleifsson, G.; McCulloch, L.J.; Ferreira, T.; Grallert, H.; Amin, N.; Wu, G.; Willer, C.J.; Raychaudhuri, S.; McCarroll, S.A.; Langenberg, C.; Hofmann, O.M.; Dupuis, J.; Qi, L.; Segrè, A.V.; van Hoek, M.; Navarro, P.; Ardlie, K.; Balkau, B.; Benediktsson, R.; Bennett, A.J.; Blagieva, R.; Boerwinkle, E.; Bonnycastle, L.L.; Boström, K.B.; Bravenboer, B.; Bumpstead, S.; Burtt, N.P.; Charpentier, G.; Chines, P.S.; Cornelis, M.; Couper, D.J.; Crawford, G.; Doney, A.S.F.; Elliott, K.S.; Elliott, A.L.; Erdos, M.R.; Fox, C.S.; Franklin, C.S.; Ganser, M.; Gieger, C.; Grarup, N.; Green, T.; Griffin, S.; Groves, C.J.; Guiducci, C.; Hadjadj, S.; Hassanali, N.; Herder, C.; Isomaa, B.; Jackson, A.U.; Johnson, P.R.V.; Jørgensen, T.; Kao, W.H.L.; Klopp, N.; Kong, A.; Kraft, P.; Kuusisto, J.; Lauritzen, T.; Li, M.; Lieverse, A.; Lindgren, C.M.; Lys-senko, V.; Marre, M.; Meitinger, T.; Midthjell, K.; Morken, M.A.; Narisu, N.; Nilsson, P.; Owen, K.R.; Payne, F.; Perry, J.R.B.; Petersen, A.K.; Platou, C.; Proença, C.; Prokopenko, I.; Rathmann, W.; Rayner, N.W.; Robertson, N.R.; Rocheleau, G.; Roden, M.; Sampson, M.J.; Saxena, R.; Shields, B.M.; Shrader, P.; Sigurdsson, G.; Sparsø, T.; Strassburger, K.; Stringham, H.M.; Sun, Q.; Swift, A.J.; Thorand, B.; Ti-chet, J.; Tuomi, T.; van Dam, R.M.; van Haeften, T.W.; van Herpt, T.; van Vliet-Ostaptchouk, J.V.; Walters, G.B.; Weedon, M.N.; Wijmen-ga, C.; Witteman, J.; Bergman, R.N.; Cauchi, S.; Collins, F.S.; Gloyn, A.L.; Gyllensten, U.; Hansen, T.; Hide, W.A.; Hitman, G.A.; Hofman, A.; Hunter, D.J.; Hveem, K.; Laakso, M.; Mohlke, K.L.; Morris, A.D.; Palmer, C.N.A.; Pramstaller, P.P.; Rudan, I.; Sijbrands, E.; Stein, L.D.; Tuomilehto, J.; Uitterlinden, A.; Walker, M.; Wareham, N.J.; Watanabe, R.M.; Abecasis, G.R.; Boehm, B.O.; Campbell, H.; Daly, M.J.; Hattersley, A.T.; Hu, F.B.; Meigs, J.B.; Pankow, J.S.; Pedersen, O.; Wichmann, H.E.; Barroso, I.; Florez, J.C.; Frayling, T.M.; Groop, L.; Sladek, R.; Thorsteinsdottir, U.; Wilson, J.F.; Illig, T.; Froguel, P.; van Duijn, C.M.; Stefansson, K.; Altshuler, D.; Boehnke, M.; McCarthy, M.I. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat. Genet., 2010, 42(7), 579-589.
[http://dx.doi.org/10.1038/ng.609] [PMID: 20581827]
[50]
Travers, M.E.; Mackay, D.J.G.; Dekker Nitert, M.; Morris, A.P.; Lindgren, C.M.; Berry, A.; Johnson, P.R.; Hanley, N.; Groop, L.C.; McCarthy, M.I.; Gloyn, A.L. Insights into the molecular mechanism for type 2 diabetes susceptibility at the KCNQ1 locus from temporal changes in imprinting status in human islets. Diabetes, 2013, 62(3), 987-992.
[http://dx.doi.org/10.2337/db12-0819] [PMID: 23139357]
[51]
Sandhu, M.S.; Weedon, M.N.; Fawcett, K.A.; Wasson, J.; Debenham, S.L.; Daly, A.; Lango, H.; Frayling, T.M.; Neumann, R.J.; Sherva, R.; Blech, I.; Pharoah, P.D.; Palmer, C.N.A.; Kimber, C.; Tavendale, R.; Morris, A.D.; McCarthy, M.I.; Walker, M.; Hitman, G.; Glaser, B.; Permutt, M.A.; Hattersley, A.T.; Wareham, N.J.; Barroso, I. Common variants in WFS1 confer risk of type 2 diabetes. Nat. Genet., 2007, 39(8), 951-953.
[http://dx.doi.org/10.1038/ng2067] [PMID: 17603484]
[52]
Pulido, R. Retraction for Berthier et al. PINK1 regulates histone H3 trimethylation and gene expression by interaction with the polycomb protein EED/WAIT1. Proc. Natl. Acad. Sci., 2014, 111(45), 16225.
[http://dx.doi.org/10.1073/pnas.1419354111] [PMID: 25331905]
[53]
Haghvirdizadeh, P; Mohamed, Z; Abdullah, NA; Haghvirdizadeh, P; Haerian, MS; Haerian, BS KCNJ11: Genetic polymorphisms and risk of diabetes mellitus. J Diabetes Res., 2015, 2015
[54]
Gloyn, A.L.; Reimann, F.; Girard, C.; Edghill, E.L.; Proks, P.; Pearson, E.R.; Temple, I.K.; Mackay, D.J.G.; Shield, J.P.H.; Freedenberg, D.; Noyes, K.; Ellard, S.; Ashcroft, F.M.; Gribble, F.M.; Hattersley, A.T. Relapsing diabetes can result from moderately activating mutations in KCNJ11. Hum. Mol. Genet., 2005, 14(7), 925-934.
[http://dx.doi.org/10.1093/hmg/ddi086] [PMID: 15718250]
[55]
Small, K.S.; Todorčević, M.; Civelek, M.; El-Sayed Moustafa, J.S.; Wang, X.; Simon, M.M.; Fernandez-Tajes, J.; Mahajan, A.; Horikoshi, M.; Hugill, A.; Glastonbury, C.A.; Quaye, L.; Neville, M.J.; Sethi, S.; Yon, M.; Pan, C.; Che, N.; Viñuela, A.; Tsai, P.C.; Nag, A.; Buil, A.; Thorleifsson, G.; Raghavan, A.; Ding, Q.; Morris, A.P.; Bell, J.T.; Thorsteinsdottir, U.; Stefansson, K.; Laakso, M.; Dahlman, I.; Arner, P.; Gloyn, A.L.; Musunuru, K.; Lusis, A.J.; Cox, R.D.; Karpe, F.; McCarthy, M.I. Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition. Nat. Genet., 2018, 50(4), 572-580.
[http://dx.doi.org/10.1038/s41588-018-0088-x] [PMID: 29632379]
[56]
Shahvazian, E.; Mahmoudi, M.B.; Farashahi Yazd, E.; Gharibi, S.; Moghimi, B. HosseinNia, P.; Mirzaei, M. The KLF14 Variant is Asso-ciated with Type 2 Diabetes and HbA1C Level. Biochem. Genet., 2021, 59(2), 574-588.
[http://dx.doi.org/10.1007/s10528-020-10015-w] [PMID: 33389382]
[57]
Chiefari, E.; Tanyolaç, S.; Paonessa, F.; Pullinger, C.R.; Capula, C.; Iiritano, S.; Mazza, T.; Forlin, M.; Fusco, A.; Durlach, V.; Durlach, A.; Malloy, M.J.; Kane, J.P.; Heiner, S.W.; Filocamo, M.; Foti, D.P.; Goldfine, I.D.; Brunetti, A. Functional variants of the HMGA1 gene and type 2 diabetes mellitus. JAMA, 2011, 305(9), 903-912.
[http://dx.doi.org/10.1001/jama.2011.207] [PMID: 21364139]
[58]
Silander, K.; Mohlke, K.L.; Scott, L.J.; Peck, E.C.; Hollstein, P.; Skol, A.D.; Jackson, A.U.; Deloukas, P.; Hunt, S.; Stavrides, G.; Chines, P.S.; Erdos, M.R.; Narisu, N.; Conneely, K.N.; Li, C.; Fingerlin, T.E.; Dhanjal, S.K.; Valle, T.T.; Bergman, R.N.; Tuomilehto, J.; Watanabe, R.M.; Boehnke, M.; Collins, F.S. Genetic variation near the hepatocyte nuclear factor-4 α gene predicts susceptibility to type 2 diabetes. Diabetes, 2004, 53(4), 1141-1149.
[http://dx.doi.org/10.2337/diabetes.53.4.1141] [PMID: 15047633]
[59]
Boden, G. Obesity and free fatty acids. Endocrinol. Metab. Clin. North Am., 2008, 37(3), 635-646.
[http://dx.doi.org/10.1016/j.ecl.2008.06.007] [PMID: 18775356]
[60]
Portha, B; Chavey, A; Movassat, J Early-life origins of type 2 diabetes: Fetal programming of the beta-cell mass. Exp. Diabetes Res., 2011, 2011, 105076.
[http://dx.doi.org/10.1155/2011/105076]
[61]
Finol, F.; Parra, N.; Parra, M. PPAR- g agonists and their role in type 2 diabetes mellitus management. Am. J. Ther., 2010, 17(3), 274-283.
[62]
Matveyenko, A.V.; Butler, P.C. Relationship between β-cell mass and diabetes onset. Diabetes Obes. Metab., 2008, 10(4)(Suppl. 4), 23-31.
[http://dx.doi.org/10.1111/j.1463-1326.2008.00939.x] [PMID: 18834430]
[63]
Pan, A.; Lucas, M.; Sun, Q.; van Dam, R.M.; Franco, O.H.; Manson, J.E.; Willett, W.C.; Ascherio, A.; Hu, F.B. Bidirectional association between depression and type 2 diabetes mellitus in women. Arch. Intern. Med., 2010, 170(21), 1884-1891.
[http://dx.doi.org/10.1001/archinternmed.2010.356] [PMID: 21098346]
[64]
Nouwen, A.; Winkley, K.; Twisk, J.; Lloyd, C.E.; Peyrot, M.; Ismail, K.; Pouwer, F. Type 2 diabetes mellitus as a risk factor for the onset of depression: A systematic review and meta-analysis. Diabetologia, 2010, 53(12), 2480-2486.
[http://dx.doi.org/10.1007/s00125-010-1874-x] [PMID: 20711716]
[65]
Holman, R.R.; Paul, S.K.; Bethel, M.A.; Matthews, D.R.; Neil, H.A.W. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med., 2008, 359(15), 1577-1589.
[http://dx.doi.org/10.1056/NEJMoa0806470] [PMID: 18784090]
[66]
Feng, X.; Scott, A.; Wang, Y.; Wang, L.; Zhao, Y.; Doerner, S.; Satake, M.; Croniger, C.M.; Wang, Z. PTPRT regulates high-fat diet-induced obesity and insulin resistance. PLoS One, 2014, 9(6), e100783.
[http://dx.doi.org/10.1371/journal.pone.0100783] [PMID: 24949727]
[67]
Boden, G. Free fatty acids FFA a link between obesity and insulin resistance. Front. Biosci., 1998, 3(4), A272.
[http://dx.doi.org/10.2741/A272] [PMID: 9450985]
[68]
Yehualashet, A.S. Toll-like receptors as a potential drug target for diabetes mellitus and diabetes-associated complications. Diabetes. Diabetes Metab. Syndr. Obes., 2020, 13, 4763-4777.
[http://dx.doi.org/10.2147/DMSO.S274844] [PMID: 33311992]
[69]
Ichimura, A.; Hasegawa, S.; Kasubuchi, M.; Kimura, I. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front. Pharmacol., 2014, 5(11), 1-7.
[http://dx.doi.org/10.3389/fphar.2014.00236]
[70]
Rangwala, S.M.; Lazar, M.A. Peroxisome proliferator-activated receptor g in diabetes and metabolism. Trends Pharmacol. Sci., 2004, 25(6), 331-336.
[http://dx.doi.org/10.1016/j.tips.2004.03.012]
[71]
Sun, J.; Qu, C.; Wang, Y.; Huang, H.; Zhang, M.; Zou, W. Type 2 diabetes mellitus and protein-tyrosine phosphatase 1b. J. Diabetes. Metab. Disord. Control, 2016, 3(8), 180-183.
[http://dx.doi.org/10.15406/jdmdc.2016.03.00096]
[72]
Singh, S.; Singh Grewal, A.; Grover, R.; Sharma, N.; Chopra, B.; Kumar Dhingra, A.; Arora, S.; Redhu, S.; Lather, V. Recent updates on development of protein-tyrosine phosphatase 1B inhibitors for treatment of diabetes, obesity and related disorders. Bioorg. Chem., 2022, 121(4), 105626.
[http://dx.doi.org/10.1016/j.bioorg.2022.105626] [PMID: 35255350]
[73]
Grewal, A.S.; Bhardwaj, S.; Pandita, D.; Lather, V.; Sekhon, B.S. Updates on aldose reductase inhibitors for management of diabetic complica-tions and non-diabetic diseases. Mini Rev. Med. Chem., 2016, 16(2), 120-162.
[74]
Padhi, S.; Nayak, A.K.; Behera, A. Type II diabetes mellitus: a review on recent drug based therapeutics. Biomed. Pharmacother., 2020, 131, 110708.
[http://dx.doi.org/10.1016/j.biopha.2020.110708] [PMID: 32927252]
[75]
Bhattacharya, S.; Rathore, A.; Parwani, D.; Mallick, C.; Asati, V.; Agarwal, S.; Rajoriya, V.; Das, R.; Kashaw, S.K. An exhaustive perspec-tive on structural insights of SGLT2 inhibitors: A novel class of antidiabetic agent. Eur. J. Med. Chem., 2020, 204, 112523.
[http://dx.doi.org/10.1016/j.ejmech.2020.112523] [PMID: 32717480]
[76]
Deacon, CF Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus. Nat. Rev. Endocrinol., 2020, 16(11), 642-653.
[http://dx.doi.org/10.1038/s41574-020-0399-8]
[77]
Overton, H.A.; Fyfe, M.C.T.; Reynet, C. GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Br. J. Pharmacol., 2008, 153(Suppl. 1), S76-S81.
[78]
Zhao, J.; Zhao, Y.; Hu, Y.; Peng, J. Targeting the GPR119/incretin axis: a promising new therapy for metabolic-associated fatty liver disea-se. Cell. Mol. Biol. Lett., 2021, 26(1), 32.
[http://dx.doi.org/10.1186/s11658-021-00276-7]
[79]
Dhayal, S.; and Morgan, N.G. 2010. The significance of GPR119 agonists as a future treatment for type 2 diabetes. Drug News Perspect., 2010, 23(7), 418-424.
[80]
Im, D.S. 2021. GPR119 and GPR55 as receptors for fatty acid ethanolamides, oleoylethanolamide and palmitoylethanolamide. Int. J. Mol. Sci., 2021, 22(3), 1034.
[81]
Tyurenkov, I.N.; Kurkin, D.V.; Bakulin, D.A.; Volotova, E. V Chemistry and Hypoglycemic Activity of GPR119 Agonist ZB-16. Front. Endocrinol., 2018, 9, 543.
[http://dx.doi.org/10.3389/fendo.2018.00543]
[82]
Ritter, K.; Buning, C.; Halland, N.; Po, C.; Schwink, L.G. G protein-coupled receptor 119 (gpr119) agonists for the treatment of diabetes: recent progress and prevailing challenges. J. Med. Chem., 2016, 59(8), 3579-3592.
[83]
Godlewski, G.; Offertáler, L.; Wagner, J.A. Kunos, G Receptors for acylethanolamides — GPR55 and GPR119. Prostaglandins Other Lipid Mediat., 2009, 89, 105-111.
[84]
Gpr, S Mutation-guided unbiased modeling of the fat resource mutation-guided unbiased modeling of the fat sensor GPR119 for high-yield agonist screening. Struct. Des., 2015, 1-10.
[85]
Yang, J.W. Kim, HS Therapeutic application of GPR119 ligands in metabolic disorders. Diabetes Obes. Metab., 2018, 20(2), 257-269.
[86]
Highlights, M. G-protein-coupled receptors: New approaches to maximise the impact of GPCRS in drug discovery. Expert Opin. Ther. Targets, 2004, 8(2), 165-170.
[http://dx.doi.org/10.1517/14728222.8.2.165]
[87]
Fredriksson, R.; Gloriam, D.E.I.; Lagerstro, M.C. Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett., 2003, 554(3), 381-388.
[http://dx.doi.org/10.1016/S0014-5793(03)01196-7]
[88]
liang, C.Z.; Jones, RM.; He, H. A Role for -Cell-expressed g protein-coupled receptor 119 in glycemic control by enhancing Glucose- Dependent insulin release. 2015, 148(5), 2601-2609.
[89]
Odori, S.; Hosoda, K.; Tomita, T.; Fujikura, J.; Kusakabe, T.; Kawaguchi, Y.; Doi, R.; Takaori, K.; Ebihara, K.; Sakai, Y.; Uemoto, S.; Nakao, K. GPR119 expression in normal human tissues and islet cell tumors: Evidence for its islet-gastrointestinal distribution, expres-sion in pancreatic beta and alpha cells, and involvement in islet function. Metabolism, 2013, 62(1), 70-78.
[http://dx.doi.org/10.1016/j.metabol.2012.06.010] [PMID: 22883930]
[90]
Ahlkvist, L.; Brown, K.; Ahre, B. Upregulated insulin secretion in insulin-resistant mice : evidence of increased islet GLP1 receptor levels and GPR119-activated GLP1 secretion. Endocr. Connect., 2013, 2(2), 69-78.
[http://dx.doi.org/10.1530/EC-12-0079]
[91]
Engelstoft, M.S.; Norn, C.; Hauge, M.; Holliday, N.D.; Elster, L. Structural basis for constitutive activity and agonist-induced activation of the enteroendocrine fat sensor GPR119 Tables of Links. Br. J. Pharmacol., 2014, 171(24), 5774-5789.
[http://dx.doi.org/10.1111/bph.12877]
[92]
Ohishi, T.; Yoshida, S. The therapeutic potential of GPR119 agonists for type 2 diabetes. Expert Opin. Investig. Drugs, 2012, 21(3), 321-328.
[http://dx.doi.org/10.1517/13543784.2012.657797]
[93]
Oh, D.Y.; Olefsky, J.M. G protein-coupled receptors as targets for anti-diabetic therapeutics. Nat. Rev. Drug Discov., 2016, 15(3), 161-172.
[http://dx.doi.org/10.1038/nrd.2015.4] [PMID: 26822831]
[94]
Hamaguchi, K.; Gaskins, H.R.; Leiter, E.H. NIT-1, a pancreatic β-cell line established from a transgenic NOD/Lt mouse. Diabetes, 1991, 40(7), 842-849.
[http://dx.doi.org/10.2337/diab.40.7.842] [PMID: 1647994]
[95]
Miyazaki, S.; Tashiro, F.; Tsuchiya, T.; Sasaki, K.; Miyazaki, J. Establishment of a long-term stable β-cell line and its application to analyze the effect of Gcg expression on insulin secretion. Sci. Rep., 2021, 11(1), 477.
[http://dx.doi.org/10.1038/s41598-020-79992-7] [PMID: 33414495]
[96]
Santerre, RF; Cook, RA Crisel, Insulin synthesis in a clonal cell line of simian virus 40-transformed hamster pancreatic beta cells. Proc Natl Acad Sci, 1981, 78(7 I), 4339-4343.
[97]
Efrat, S.; Linde, S.; Kofod, H.; Spector, D.; Delannoy, M.; Grant, S.; Hanahan, D.; Baekkeskov, S. Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene. Proc. Natl. Acad. Sci., 1988, 85(23), 9037-9041.
[http://dx.doi.org/10.1073/pnas.85.23.9037] [PMID: 2848253]
[98]
Miyazaki, J.I.; Araki, K.; Yamato, E.; Ikegami, H.; Asano, T.; Shibasaki, Y.; Oka, Y.; Yamamura, K.I. Establishment of a pancreatic β cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms. Endocrinology, 1990, 127(1), 126-132.
[http://dx.doi.org/10.1210/endo-127-1-126] [PMID: 2163307]
[99]
Asfari, M.; Janjic, D.; Meda, P.; Li, G.; Halban, P.A.; Wollheim, C.B. Establishment Differentiated. Endocrinology, 1992, 130(1), 167-178.
[http://dx.doi.org/10.1210/endo.130.1.1370150] [PMID: 1370150]
[100]
Noda, M.; Komatsu, M.; Sharp, G.W.G. The betaHC-9 pancreatic β-cell line preserves the characteristics of progenitor mouse islets. Diabetes, 1996, 45(12), 1766-1773.
[http://dx.doi.org/10.2337/diab.45.12.1766] [PMID: 8922364]
[101]
Kobayashi, M.; Yamato, E.; Tanabe, K.; Tashiro, F.; Miyazaki, S.; Miyazaki, J. Functional analysis of novel candidate regulators of insulin secretion in the MIn6 mouse pancreatic β cell line. PLoS One, 2016, 11(3), e0151927.
[http://dx.doi.org/10.1371/journal.pone.0151927] [PMID: 26986842]
[102]
Berner, A.; Bachmann, M.; Bender, C.; Pfeilschifter, J.; Christen, U.; Mühl, H. Though active on RINm5F insulinoma cells and cultured pancreatic islets, recombinant IL-22 fails to modulate cytotoxicity and disease in a protocol of streptozotocin-induced experimental diabe-tes. Front. Pharmacol., 2016, 6(1), 317.
[http://dx.doi.org/10.3389/fphar.2015.00317] [PMID: 26793108]
[103]
Gpr, F.F.A.; Engelstoft, M.S. GPR119, a major enteroendocrine sensor of dietary triglyceride metabolites coacting in synergy with FFA1 (GPR40). Endocrinology, 2016, 157(12), 4561-4569.
[http://dx.doi.org/10.1210/en.2016-1334]
[104]
Hansen, K.B.; Rosenkilde, M.M.; Knop, F.K. 2-Oleoyl glycerol Is a GPR119 agonist and signals GLP-1 release in humans. J. Clin. Endocrinol. Metab., 2011, 96(9), E1409-E1417.
[http://dx.doi.org/10.1210/jc.2011-06472011]
[105]
Kleberg, K.; Nielsen, L.L.; Stuhr-hansen, N.; Nielsen, J. Evaluation of the immediate vascular stability of lipoprotein lipase-generated 2-monoacylglycerol in mice. Biofactors, 2014, 40(6), 596-602.
[http://dx.doi.org/10.1002/biof.1189]
[106]
Tough, I.R.; Forbes, S.; Herzog, H.; Jones, R.M.; Schwartz, T.W.; Cox, H.M. Bidirectional GPR119 Agonism Requires Peptide YY and Glucose for Activity in Mouse and Human Colon Mucosa. Endocrinology, 2018, 159(4), 1704-1717.
[http://dx.doi.org/10.1210/en.2017-03172]
[107]
liang, C.Z; Carroll, C.; Chen, R. N-oleoyldopamine enhances glucose homeostasis through the activation of GPR119. Mol. Endocrinol., 2010, 24(1), 161-170.
[108]
Soga, T.; Ohishi, T.; Matsui, T. Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem. Biophys. Res. Commun., 2005, 326(4), 744-751.
[http://dx.doi.org/10.1016/j.bbrc.2004.11.120]
[109]
Kogure, R.; Toyama, K.; Hiyamuta, S.; Kojima, I.; Takeda, S. 5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion. Biochem. Biophys. Res. Commun., 2011, 416(1-2), 58-63.
[http://dx.doi.org/10.1016/j.bbrc.2011.10.141] [PMID: 22079287]
[110]
Semple, G.; Ren, A.; Fioravanti, B.; Pereira, G.; Calderon, I.; Choi, K.; Xiong, Y.; Shin, Y.J.; Gharbaoui, T.; Sage, C.R.; Morgan, M.; Xing, C.; Chu, Z.L.; Leonard, J.N.; Grottick, A.J.; Al-Shamma, H.; Liang, Y.; Demarest, K.T.; Jones, R.M. Discovery of fused bicyclic agonists of the orphan G-protein coupled receptor GPR119 with in vivo activity in rodent models of glucose control. Bioorg. Med. Chem. Lett., 2011, 21(10), 3134-3141.
[http://dx.doi.org/10.1016/j.bmcl.2011.03.007] [PMID: 21444206]
[111]
Semple, G.; Fioravanti, B.; Pereira, G. Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119. J. Med. Chem., 2008, 51(17), 5172-5175.
[http://dx.doi.org/10.1021/jm8006867]
[112]
liang, C.Z; Carroll, C.; Alfonso, J. A role for intestinal endocrine cell-expressed g protein-coupled receptor 119 in glycemic control by enhancing glucagon-like peptide-1 and glucose-dependent insulinotropic peptide release. Endocrinology, 2008, 149(5), 2038-2047.
[http://dx.doi.org/10.1210/en.2007-0966]
[113]
Marty, V.N.; Farokhnia, M.; Munier, J.J.; Mulpuri, Y. Long-acting glucagon-like peptide-1 receptor agonists suppress voluntary alcohol intake in male wistar rats. Front. Neurosci., 2020, 14, 599646.
[http://dx.doi.org/10.3389/fnins.2020.599646]
[114]
Negoro, K.; Yonetoku, Y.; Maruyama, T.; Yoshida, S.; Takeuchi, M.; Ohta, M. Synthesis and structure–activity relationship of 4-amino-2-phenylpyrimidine derivatives as a series of novel GPR119 agonists. Bioorg. Med. Chem., 2012, 20(7), 2369-2375.
[http://dx.doi.org/10.1016/j.bmc.2012.02.006] [PMID: 22365911]
[115]
Shah, U.; Kowalski, T.J. GPR119 Agonists for the Potential Treatment of Type 2 Diabetes and Related Metabolic Disorders. In: Vitamins & Hormones, 1st ed; Elsevier Inc., 2010, pp. 84.
[http://dx.doi.org/10.1016/B978-0-12-381517-0.00016-3]
[116]
Zhu, X.; Huang, D.; Lan, X. European Journal of Medicinal Chemistry The fi rst pharmacophore model for potent G protein-coupled re-ceptor 119 agonist. Eur. J. Med. Chem., 2011, 46(7), 2901-2907.
[http://dx.doi.org/10.1016/j.ejmech.2011.04.014] [PMID: 21524831]
[117]
Kang, S-U. GPR119 agonists: A promising approach for T2DM treatment? A SWOT analysis of GPR119. Drug Discov. Today, 2013, 18(23-24), 1309-1315.
[http://dx.doi.org/10.1016/j.drudis.2013.09.011]
[118]
Hansen, H.S.; Rosenkilde, M.M.; Holst, J.J.; Schwartz, T.W. GPR119 as a fat sensor. Trends Pharmacol. Sci., 2012, 33(7), 374-381.
[http://dx.doi.org/10.1016/j.tips.2012.03.014]
[119]
Semple, G.; Lehmann, J.; Wong, A.; Ren, A.; Bruce, M.; Shin, Y.J.; Sage, C.R.; Morgan, M.; Chen, W.C.; Sebring, K.; Chu, Z.L.; Leonard, J.N.; Al-Shamma, H.; Grottick, A.J.; Du, F.; Liang, Y.; Demarest, K.; Jones, R.M. Discovery of a second generation agonist of the orphan G-protein coupled receptor GPR119 with an improved profile. Bioorg. Med. Chem. Lett., 2012, 22(4), 1750-1755.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.092] [PMID: 22264481]
[120]
Watada, H.; Shiramoto, M.; Myobatake, Y.; Taguchi, T. G protein-coupled receptor 119 agonist DS-8500a effects on pancreatic b -cells in Japanese type 2 diabetes mellitus patients. J. Diabetes Investig., 2019, 10(1), 84-93.
[http://dx.doi.org/10.1111/jdi.12849]
[121]
Kato, M.; Furuie, H.; Kamiyama, E.; Shiosakai, K. Safety and pharmacokinetics of DS-8500a, a novel GPR119 agonist, after multiple oral doses in healthy japanese males. Clin. Drug Investig., 2018, 38(6), 519-525.
[http://dx.doi.org/10.1007/s40261-018-0633-5]
[122]
Matsumoto, K.; Yoshitomi, T.; Ishimoto, Y.; Tanaka, N.; Takahashi, K. DS-8500a, an orally available g protein-coupled receptor 119 ago-nist, upregulates glucagon-like peptide-1 and enhances glucose-dependent insulin secretion and improves glucose homeostasis in type 2 diabetic rats. J. Pharmacol. Exp. Ther., 2018, 367(3), 509-517.
[http://dx.doi.org/10.1124/jpet.118.250019]
[123]
Katamreddy, S. R.; Carpenter, A. J.; Ammala, C. E.; Boros, E. E.; Brashear, R. L.; Briscoe, C. P.; Bullard, S. R.; Caldwell, R. D.; Conlee, C. R.; Croom, D. K.; Hart, S. M.; Heyer, D. O.; Johnson, P. R.; Kashatus, J. A.; Minick, D. J.; Peckham, G. E.; Ross, S. A.; Roller, S. G.; Sa-mano, V. A.; Sauls, H. R. Discovery of 6,7- Dihydro-5H-Pyrrolo[2,3-A]Pyrimidines as orally available G protein- coupled receptor 119 agonists. J. Med. Chem., 2012, 55(24), 10972-10994.
[http://dx.doi.org/10.1021/jm301404a]
[124]
Hothersall, J.D.; Bussey, C.E.; Brown, A.J.; Scott, J.S.; Dale, I.; Rawlins, P. Sustained wash-resistant receptor activation responses of GPR119 agonists. Eur. J. Pharmacol., 2015, 762, 430-442.
[http://dx.doi.org/10.1016/j.ejphar.2015.06.031] [PMID: 26101059]
[125]
Kim, H.J.; Choi, J.Y.; Che, X. G protein‐coupled receptor 119 is involved in RANKL‐induced osteoclast differentiation and fusion. J. Cell. Physiol., 2019, 234(7), 11490-11499.
[http://dx.doi.org/10.1002/jcp.27805]
[126]
Yoshida, S.; Ohishi, T.; Matsui, T.; Tanaka, H.; Oshima, H.; Yonetoku, Y.; Shibasaki, M. Novel GPR119 agonist AS1535907 contributes to first-phase insulin secretion in rat perfused pancreas and diabetic db/db mice. Biochem. Biophys. Res. Commun., 2010, 402(2), 280-285.
[http://dx.doi.org/10.1016/j.bbrc.2010.10.015] [PMID: 20937249]
[127]
Yoshida, S.; Ohishi, T.; Matsui, T. The role of small molecule GPR119 agonist, AS1535907, in glucose-stimulated insulin secretion and pancreatic β-cell function. Diabetes Obesity and Metab., 2011, 13(1), 34-41.
[128]
Yoshida, S.; Tanaka, H.; Oshima, H. Biochemical and Biophysical Research Communications AS1907417, a novel GPR119 agonist, as an insulinotropic and b -cell preservative agent for the treatment of type 2 diabetes. Biochem. Biophys. Res. Commun., 2010, 400(4), 745-751.
[http://dx.doi.org/10.1016/j.bbrc.2010.08.141] [PMID: 20816753]
[129]
Oshima, H.; Yoshida, S.; Ohishi, T.; Matsui, T.; Tanaka, H.; Yonetoku, Y.; Shibasaki, M.; Uchiyama, Y. Novel GPR119 agonist AS1669058 potentiates insulin secretion from rat islets and has potent anti-diabetic effects in ICR and diabetic db/db mice. Life Sci., 2013, 92(2), 167-173.
[http://dx.doi.org/10.1016/j.lfs.2012.11.015] [PMID: 23246743]
[130]
Free, C.; Christopherson, J. Chen, Q Activation of GPR119 stimulates human β-cell replication and neogenesis in humanized mice with functional human islets. J. Diabetes Res., 2016, 2016, 1620821.
[http://dx.doi.org/10.1155/2016/1620821]
[131]
Overton, H.A.; Babbs, A.J. Doel, SM Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small- molecule hypophagic agents. Cell Metab., 2006, 3(3), 167-175.
[132]
GPR119 agonists as potential new oral agents for the treatment of type 2 diabetes and obesity. Expert Opin. Drug Discov., 2008, 3(4), 403-413.
[133]
Kim, S.R.; Kim, D.H.; Park, S.H. In vivo efficacy of HD0471953 : A novel gpr119 agonist for the treatment of type 2 diabetes mellitus. J. Diabetes Res., 2013, 2013, 269569.
[134]
Kim, S.; Kim, D.H. HD047703, a new promising anti-diabetic drug candidate: In vivo preclinical studies. Biomol. Ther., 2014, 22(5), 400-405.
[135]
Kim, T.Y. seok, HY.; Hwa, C. Novel GPR119 agonist HD0471042 attenuated type 2 diabetes mellitus. Arch. Pharm. Res., 2014, 37(5), 671-678.
[136]
Huan, Y.; Jiang, Q.; Li, G. The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo. Scientific. Reports, 2017, 7(5), 1-11.
[137]
Harada, K.; Mizukami, J.; Watanabe, T.; Mori, G.; Ubukata, M.; Suwa, K.; Fukuda, S.; Negoro, T.; Sato, M.; Inaba, T. Lead generation and optimization of novel GPR119 agonists with a spirocyclic cyclohexane structure. Bioorg. Med. Chem. Lett., 2019, 29(3), 373-379.
[http://dx.doi.org/10.1016/j.bmcl.2018.12.041] [PMID: 30587450]
[138]
Syed, S.K.; Bui, H.H. Beavers, LS Regulation of GPR119 receptor activity with endocannabinoid-like lipids Regulation of GPR119 receptor activity with endocannabinoid-like lipids. Am. J. Physiol. Endocrinol. Metab., 2012, 303(12), E1469-E1478.
[139]
Polli, J.W.; Hussey, E.; Bush, M. Evaluation of drug interactions of GSK1292263 (a GPR119 agonist) with statins: from in vitro data to clini-cal study design. Xenobiotica, 2013, 43(6), 498-508.
[http://dx.doi.org/10.3109/00498254.2012.739719]
[140]
Agonist, A.G.P.R.; Gao, J.; Tian, L. Stimulating b -cell replication and improving islet graft function by AR231453, AGPR119 agonist. TPS, 2011, 43(9), 3217-3220.
[PMID: 22099761]
[141]
Gao, J.; Tian, L.; Weng, G. Stimulating beta cell replication and improving islet graft function by GPR119 agonists. Transpl. Int., 2011, 24, 1124-1134.
[http://dx.doi.org/10.1111/j.1432-2277.2011.01332.x]
[142]
Fang, Y.; Yang, Z.; Gundeti, S.; Lee, J.; Park, H. Novel 5- Nitropyrimidine Derivatives Bearing Endo-Azabicyclic Alcohols/ Amines as Potent GPR119 Agonists. Bioorg. Med. Chem., 2017, 25(1), 254-260.
[http://dx.doi.org/10.1016/j.bmc.2016.10.030]
[143]
Chen, J.; Sang, Z.; Li, L.; He, L.; Ma, L. Discovery of 5-methyl-2- (4- ((4- (methylsulfonyl) benzyl)oxy) phenyl) -4- (piperazin-1-yl) pyrimidine derivatives as novel GRP119 agonists for the treatment of diabetes and obesity. Mol. Divers., 2017, 21(3), 637-654.
[144]
Yang, Z.; Fang, Y.; Park, H. Synthesis and biological evaluation of pyrimidine derivatives with diverse azabicyclic ether/amine as novel GPR119 agonist. Bioorg. Med. Chem. Lett., 2017, 27(11), 2515-2519.
[http://dx.doi.org/10.1016/j.bmcl.2017.03.092] [PMID: 28408218]
[145]
Fang, Y.; Xu, J.; Li, Z.; Yang, Z.; Xiong, L.; Jin, Y.; Wang, Q.; Xie, S.; Zhu, W.; Chang, S. Design and synthesis of novel pyrimido[5,4-d]pyrimidine derivatives as GPR119 agonist for treatment of type 2 diabetes. Bioorg. Med. Chem., 2018, 26(14), 4080-4087.
[http://dx.doi.org/10.1016/j.bmc.2018.06.035] [PMID: 30100020]
[146]
Fang, Y.; Zhang, S.; Wu, W.; Liu, Y.; Yang, J.; Li, Y.; Li, M.; Dong, H.; Jin, Y.; Liu, R.; Yang, Z. Design and synthesis of tetrahydropyri-dopyrimidine derivatives as dual GPR119 and DPP-4 modulators. Bioorg. Chem., 2020, 94(10), 103390.
[http://dx.doi.org/10.1016/j.bioorg.2019.103390] [PMID: 31662212]
[147]
Koshizawa, T.; Morimoto, T.; Watanabe, G.; Watanabe, T.; Yamasaki, N.; Sawada, Y.; Fukuda, T.; Okuda, A.; Shibuya, K.; Ohgiya, T. Optimization of a novel series of potent and orally bioavailable GPR119 agonists. Bioorg. Med. Chem. Lett., 2017, 27(15), 3249-3253.
[http://dx.doi.org/10.1016/j.bmcl.2017.06.034] [PMID: 28648463]

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