Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Developing Insulin and BDNF Mimetics for Diabetes Therapy

Author(s): Chi Bun Chan*, Palak Ahuja and Keqiang Ye

Volume 19, Issue 24, 2019

Page: [2188 - 2204] Pages: 17

DOI: 10.2174/1568026619666191010160643

Price: $65

Abstract

Diabetes is a global public health concern nowadays. The majority of diabetes mellitus (DM) patients belong to type 2 diabetes mellitus (T2DM), which is highly associated with obesity. The general principle of current therapeutic strategies for patients with T2DM mainly focuses on restoring cellular insulin response by potentiating the insulin-induced signaling pathway. In late-stage T2DM, impaired insulin production requires the patients to receive insulin replacement therapy for maintaining their glucose homeostasis. T2DM patients also demonstrate a drop of brain-derived neurotrophic factor (BDNF) in their circulation, which suggests that replenishing BDNF or enhancing its downstream signaling pathway may be beneficial. Because of their protein nature, recombinant insulin or BDNF possess several limitations that hinder their clinical application in T2DM treatment. Thus, developing orally active “insulin pill” or “BDNF pill” is essential to provide a more convenient and effective therapy. This article reviews the current development of non-peptidyl chemicals that mimic insulin or BDNF and their potential as anti-diabetic agents.

Keywords: BDNF, Diabetes, Insulin, Mimetic, Obesity, T2DM.

« Previous Next »
Graphical Abstract

[1]
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2010, 33(Suppl. 1), S62-S69.
[http://dx.doi.org/10.2337/dc10-S062] [PMID: 20042775]
[2]
DeFronzo, R.A.; Ferrannini, E.; Groop, L.; Henry, R.R.; Herman, W.H.; Holst, J.J.; Hu, F.B.; Kahn, C.R.; Raz, I.; Shulman, G.I.; Simonson, D.C.; Testa, M.A.; Weiss, R. Type 2 diabetes mellitus. Nat. Rev. Dis. Primers, 2015, 1, 15019.
[http://dx.doi.org/10.1038/nrdp.2015.19] [PMID: 27189025]
[3]
World Health Organization; Global Report on Diabetes, 2016.(Accessed . https://apps.who.int/iris/bitstream/handle/10665/204871/9789241565257_eng.pdf?sequence=1
[4]
International Diabetes Federation. IDF Diabetes Atlas, 8th edn. Brussels, Belgium: International Diabetes Federation; 2017. (Accessed. http://www.diabetesatlas.org
[5]
Collaboration, N.C.D.R.F. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet, 2016, 387(10027), 1513-1530.
[http://dx.doi.org/10.1016/S0140-6736(16)00618-8] [PMID: 27061677]
[6]
Madiraju, A.K.; Qiu, Y.; Perry, R.J.; Rahimi, Y.; Zhang, X.M.; Zhang, D.; Camporez, J.G.; Cline, G.W.; Butrico, G.M.; Kemp, B.E.; Casals, G.; Steinberg, G.R.; Vatner, D.F.; Petersen, K.F.; Shulman, G.I. Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nat. Med., 2018, 24(9), 1384-1394.
[http://dx.doi.org/10.1038/s41591-018-0125-4] [PMID: 30038219]
[7]
Owen, M.R.; Doran, E.; Halestrap, A.P. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J., 2000, 348(Pt 3), 607-614.
[http://dx.doi.org/10.1042/bj3480607] [PMID: 10839993]
[8]
Pfefferkorn, J.A.; Guzman-Perez, A.; Litchfield, J.; Aiello, R.; Treadway, J.L.; Pettersen, J.; Minich, M.L.; Filipski, K.J.; Jones, C.S.; Tu, M.; Aspnes, G.; Risley, H.; Bian, J.; Stevens, B.D.; Bourassa, P.; D’Aquila, T.; Baker, L.; Barucci, N.; Robertson, A.S.; Bourbonais, F.; Derksen, D.R.; Macdougall, M.; Cabrera, O.; Chen, J.; Lapworth, A.L.; Landro, J.A.; Zavadoski, W.J.; Atkinson, K.; Haddish-Berhane, N.; Tan, B.; Yao, L.; Kosa, R.E.; Varma, M.V.; Feng, B.; Duignan, D.B.; El-Kattan, A.; Murdande, S.; Liu, S.; Ammirati, M.; Knafels, J.; Dasilva-Jardine, P.; Sweet, L.; Liras, S.; Rolph, T.P. Discovery of (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid as a hepatoselective glucokinase activator clinical candidate for treating type 2 diabetes mellitus. J. Med. Chem., 2012, 55(3), 1318-1333.
[http://dx.doi.org/10.1021/jm2014887] [PMID: 22196621]
[9]
Erion, M.D.; van Poelje, P.D.; Dang, Q.; Kasibhatla, S.R.; Potter, S.C.; Reddy, M.R.; Reddy, K.R.; Jiang, T.; Lipscomb, W.N. MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes. Proc. Natl. Acad. Sci. USA, 2005, 102(22), 7970-7975.
[http://dx.doi.org/10.1073/pnas.0502983102] [PMID: 15911772]
[10]
Cline, G.W.; Johnson, K.; Regittnig, W.; Perret, P.; Tozzo, E.; Xiao, L.; Damico, C.; Shulman, G.I. Effects of a novel glycogen synthase kinase-3 inhibitor on insulin-stimulated glucose metabolism in Zucker diabetic fatty (fa/fa) rats. Diabetes, 2002, 51(10), 2903-2910.
[http://dx.doi.org/10.2337/diabetes.51.10.2903] [PMID: 12351425]
[11]
Rines, A.K.; Sharabi, K.; Tavares, C.D.; Puigserver, P. Targeting hepatic glucose metabolism in the treatment of type 2 diabetes. Nat. Rev. Drug Discov., 2016, 15(11), 786-804.
[http://dx.doi.org/10.1038/nrd.2016.151] [PMID: 27516169]
[12]
Ekberg, K.; Landau, B.R.; Wajngot, A.; Chandramouli, V.; Efendic, S.; Brunengraber, H.; Wahren, J. Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting. Diabetes, 1999, 48(2), 292-298.
[http://dx.doi.org/10.2337/diabetes.48.2.292] [PMID: 10334304]
[13]
Mutel, E.; Abdul-Wahed, A.; Ramamonjisoa, N.; Stefanutti, A.; Houberdon, I.; Cavassila, S.; Pilleul, F.; Beuf, O.; Gautier-Stein, A.; Penhoat, A.; Mithieux, G.; Rajas, F. Targeted deletion of liver glucose-6 phosphatase mimics glycogen storage disease type 1a including development of multiple adenomas. J. Hepatol., 2011, 54(3), 529-537.
[http://dx.doi.org/10.1016/j.jhep.2010.08.014] [PMID: 21109326]
[14]
Cavalot, F.; Petrelli, A.; Traversa, M.; Bonomo, K.; Fiora, E.; Conti, M.; Anfossi, G.; Costa, G.; Trovati, M. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. J. Clin. Endocrinol. Metab., 2006, 91(3), 813-819.
[http://dx.doi.org/10.1210/jc.2005-1005] [PMID: 16352690]
[15]
Bonora, E.; Corrao, G.; Bagnardi, V.; Ceriello, A.; Comaschi, M.; Montanari, P.; Meigs, J.B. Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus. Diabetologia, 2006, 49(5), 846-854.
[http://dx.doi.org/10.1007/s00125-006-0203-x] [PMID: 16532323]
[16]
Deeg, M.A.; Tan, M.H. Pioglitazone versus rosiglitazone: effects on lipids, lipoproteins, and apolipoproteins in head-to-head randomized clinical studies. PPAR Res., 2008, 2008520465
[http://dx.doi.org/10.1155/2008/520465] [PMID: 18769492]
[17]
Kahn, S.E.; Haffner, S.M.; Heise, M.A.; Herman, W.H.; Holman, R.R.; Jones, N.P.; Kravitz, B.G.; Lachin, J.M.; O’Neill, M.C.; Zinman, B.; Viberti, G.; Group, A.S. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N. Engl. J. Med., 2006, 355(23), 2427-2443.
[http://dx.doi.org/10.1056/NEJMoa066224] [PMID: 17145742]
[18]
Colhoun, H.M.; Livingstone, S.J.; Looker, H.C.; Morris, A.D.; Wild, S.H.; Lindsay, R.S.; Reed, C.; Donnan, P.T.; Guthrie, B.; Leese, G.P.; McKnight, J.; Pearson, D.W.; Pearson, E.; Petrie, J.R.; Philip, S.; Sattar, N.; Sullivan, F.M.; McKeigue, P. Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs. Diabetologia, 2012, 55(11), 2929-2937.
[http://dx.doi.org/10.1007/s00125-012-2668-0] [PMID: 22945303]
[19]
Mamtani, R.; Haynes, K.; Bilker, W.B.; Vaughn, D.J.; Strom, B.L.; Glanz, K.; Lewis, J.D. Association between longer therapy with thiazolidinediones and risk of bladder cancer: a cohort study. J. Natl. Cancer Inst., 2012, 104(18), 1411-1421.
[http://dx.doi.org/10.1093/jnci/djs328] [PMID: 22878886]
[20]
Ekström, N.; Svensson, A.M.; Miftaraj, M.; Franzén, S.; Zethelius, B.; Eliasson, B.; Gudbjörnsdottir, S. Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register. Diabetes Obes. Metab., 2016, 18(10), 990-998.
[http://dx.doi.org/10.1111/dom.12704] [PMID: 27282621]
[21]
Soccio, R.E.; Chen, E.R.; Lazar, M.A. Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metab., 2014, 20(4), 573-591.
[http://dx.doi.org/10.1016/j.cmet.2014.08.005] [PMID: 25242225]
[22]
Bakris, G.L.; Fonseca, V.A.; Sharma, K.; Wright, E.M. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int., 2009, 75(12), 1272-1277.
[http://dx.doi.org/10.1038/ki.2009.87] [PMID: 19357717]
[23]
Thomson, S.C.; Deng, A.; Bao, D.; Satriano, J.; Blantz, R.C.; Vallon, V. Ornithine decarboxylase, kidney size, and the tubular hypothesis of glomerular hyperfiltration in experimental diabetes. J. Clin. Invest., 2001, 107(2), 217-224.
[http://dx.doi.org/10.1172/JCI10963] [PMID: 11160138]
[24]
Wang, X.X.; Levi, J.; Luo, Y.; Myakala, K.; Herman-Edelstein, M.; Qiu, L.; Wang, D.; Peng, Y.; Grenz, A.; Lucia, S.; Dobrinskikh, E.; D’Agati, V.D.; Koepsell, H.; Kopp, J.B.; Rosenberg, A.Z.; Levi, M. SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice. J. Biol. Chem., 2017, 292(13), 5335-5348.
[http://dx.doi.org/10.1074/jbc.M117.779520] [PMID: 28196866]
[25]
Haas, B.; Eckstein, N.; Pfeifer, V.; Mayer, P.; Hass, M.D. Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin. Nutr. Diabetes, 2014, 4e143
[http://dx.doi.org/10.1038/nutd.2014.40] [PMID: 25365416]
[26]
Davies, M.J.; D’Alessio, D.A.; Fradkin, J.; Kernan, W.N.; Mathieu, C.; Mingrone, G.; Rossing, P.; Tsapas, A.; Wexler, D.J.; Buse, J.B. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia, 2018, 61(12), 2461-2498.
[http://dx.doi.org/10.1007/s00125-018-4729-5] [PMID: 30288571]
[27]
Guh, D.P.; Zhang, W.; Bansback, N.; Amarsi, Z.; Birmingham, C.L.; Anis, A.H. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health, 2009, 9, 88.
[http://dx.doi.org/10.1186/1471-2458-9-88] [PMID: 19320986]
[28]
Johnson, A.M.; Olefsky, J.M. The origins and drivers of insulin resistance. Cell, 2013, 152(4), 673-684.
[http://dx.doi.org/10.1016/j.cell.2013.01.041] [PMID: 23415219]
[29]
Randle, P.J.; Garland, P.B.; Hales, C.N.; Newsholme, E.A. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet, 1963, 1(7285), 785-789.
[http://dx.doi.org/10.1016/S0140-6736(63)91500-9] [PMID: 13990765]
[30]
Lara-Castro, C.; Garvey, W.T. Intracellular lipid accumulation in liver and muscle and the insulin resistance syndrome. Endocrinol. Metab. Clin. North Am., 2008, 37(4), 841-856.
[http://dx.doi.org/10.1016/j.ecl.2008.09.002] [PMID: 19026935]
[31]
Goodpaster, B.H.; He, J.; Watkins, S.; Kelley, D.E. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J. Clin. Endocrinol. Metab., 2001, 86(12), 5755-5761.
[http://dx.doi.org/10.1210/jcem.86.12.8075] [PMID: 11739435]
[32]
Hoy, A.J.; Bruce, C.R.; Turpin, S.M.; Morris, A.J.; Febbraio, M.A.; Watt, M.J. Adipose triglyceride lipase-null mice are resistant to high-fat diet-induced insulin resistance despite reduced energy expenditure and ectopic lipid accumulation. Endocrinology, 2011, 152(1), 48-58.
[http://dx.doi.org/10.1210/en.2010-0661] [PMID: 21106876]
[33]
Zabielski, P.; Daniluk, J.; Hady, H.R.; Markowski, A.R.; Imierska, M.; Górski, J.; Blachnio-Zabielska, A.U. The effect of high-fat diet and inhibition of ceramide production on insulin action in liver. J. Cell. Physiol., 2019, 234(2), 1851-1861.
[http://dx.doi.org/10.1002/jcp.27058] [PMID: 30067865]
[34]
Air, E.L.; Strowski, M.Z.; Benoit, S.C.; Conarello, S.L.; Salituro, G.M.; Guan, X.M.; Liu, K.; Woods, S.C.; Zhang, B.B. Small molecule insulin mimetics reduce food intake and body weight and prevent development of obesity. Nat. Med., 2002, 8(2), 179-183.
[http://dx.doi.org/10.1038/nm0202-179] [PMID: 11821903]
[35]
Stratford, S.; Hoehn, K.L.; Liu, F.; Summers, S.A. Regulation of insulin action by ceramide: dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. J. Biol. Chem., 2004, 279(35), 36608-36615.
[http://dx.doi.org/10.1074/jbc.M406499200] [PMID: 15220355]
[36]
Dobrowsky, R.T.; Kamibayashi, C.; Mumby, M.C.; Hannun, Y.A. Ceramide activates heterotrimeric protein phosphatase 2A. J. Biol. Chem., 1993, 268(21), 15523-15530.
[PMID: 8393446]
[37]
Reilly, S.M.; Saltiel, A.R. Adapting to obesity with adipose tissue inflammation. Nat. Rev. Endocrinol., 2017, 13(11), 633-643.
[http://dx.doi.org/10.1038/nrendo.2017.90] [PMID: 28799554]
[38]
Hotamisligil, G.S.; Shargill, N.S.; Spiegelman, B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science, 1993, 259(5091), 87-91.
[http://dx.doi.org/10.1126/science.7678183] [PMID: 7678183]
[39]
Feinstein, R.; Kanety, H.; Papa, M.Z.; Lunenfeld, B.; Karasik, A. Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J. Biol. Chem., 1993, 268(35), 26055-26058.
[PMID: 8253716]
[40]
Li, Z.Y.; Wang, P.; Miao, C.Y. Adipokines in inflammation, insulin resistance and cardiovascular disease. Clin. Exp. Pharmacol. Physiol., 2011, 38(12), 888-896.
[http://dx.doi.org/10.1111/j.1440-1681.2011.05602.x] [PMID: 21910745]
[41]
Corvera, S.; Gealekman, O. Adipose tissue angiogenesis: impact on obesity and type-2 diabetes. Biochim. Biophys. Acta, 2014, 1842(3), 463-472.
[http://dx.doi.org/10.1016/j.bbadis.2013.06.003] [PMID: 23770388]
[42]
Aguirre, V.; Uchida, T.; Yenush, L.; Davis, R.; White, M.F. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J. Biol. Chem., 2000, 275(12), 9047-9054.
[http://dx.doi.org/10.1074/jbc.275.12.9047] [PMID: 10722755]
[43]
Reinhard, C.; Shamoon, B.; Shyamala, V.; Williams, L.T. Tumor necrosis factor alpha-induced activation of c-jun N-terminal kinase is mediated by TRAF2. EMBO J., 1997, 16(5), 1080-1092.
[http://dx.doi.org/10.1093/emboj/16.5.1080] [PMID: 9118946]
[44]
de Alvaro, C.; Teruel, T.; Hernandez, R.; Lorenzo, M. Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner. J. Biol. Chem., 2004, 279(17), 17070-17078.
[http://dx.doi.org/10.1074/jbc.M312021200] [PMID: 14764603]
[45]
Ofei, F.; Hurel, S.; Newkirk, J.; Sopwith, M.; Taylor, R. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes, 1996, 45(7), 881-885.
[http://dx.doi.org/10.2337/diab.45.7.881] [PMID: 8666137]
[46]
Paquot, N.; Castillo, M.J.; Lefèbvre, P.J.; Scheen, A.J. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J. Clin. Endocrinol. Metab., 2000, 85(3), 1316-1319.
[PMID: 10720082]
[47]
Rekedal, L.R.; Massarotti, E.; Garg, R.; Bhatia, R.; Gleeson, T.; Lu, B.; Solomon, D.H. Changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic diseases. Arthritis Rheum., 2010, 62(12), 3569-3573.
[http://dx.doi.org/10.1002/art.27703] [PMID: 20722019]
[48]
Salvadó, L.; Palomer, X.; Barroso, E.; Vázquez-Carrera, M. Targeting endoplasmic reticulum stress in insulin resistance. Trends Endocrinol. Metab., 2015, 26(8), 438-448.
[http://dx.doi.org/10.1016/j.tem.2015.05.007] [PMID: 26078196]
[49]
Ozcan, U.; Cao, Q.; Yilmaz, E.; Lee, A.H.; Iwakoshi, N.N.; Ozdelen, E.; Tuncman, G.; Görgün, C.; Glimcher, L.H.; Hotamisligil, G.S. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science, 2004, 306(5695), 457-461.
[http://dx.doi.org/10.1126/science.1103160] [PMID: 15486293]
[50]
Koh, H.J.; Toyoda, T.; Didesch, M.M.; Lee, M.Y.; Sleeman, M.W.; Kulkarni, R.N.; Musi, N.; Hirshman, M.F.; Goodyear, L.J. Tribbles 3 mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle. Nat. Commun., 2013, 4, 1871.
[http://dx.doi.org/10.1038/ncomms2851] [PMID: 23695665]
[51]
Sharma, N.K.; Das, S.K.; Mondal, A.K.; Hackney, O.G.; Chu, W.S.; Kern, P.A.; Rasouli, N.; Spencer, H.J.; Yao-Borengasser, A.; Elbein, S.C. Endoplasmic reticulum stress markers are associated with obesity in nondiabetic subjects. J. Clin. Endocrinol. Metab., 2008, 93(11), 4532-4541.
[http://dx.doi.org/10.1210/jc.2008-1001] [PMID: 18728164]
[52]
Gregor, M.F.; Yang, L.; Fabbrini, E.; Mohammed, B.S.; Eagon, J.C.; Hotamisligil, G.S.; Klein, S. Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Diabetes, 2009, 58(3), 693-700.
[http://dx.doi.org/10.2337/db08-1220] [PMID: 19066313]
[53]
Ozcan, U.; Yilmaz, E.; Ozcan, L.; Furuhashi, M.; Vaillancourt, E.; Smith, R.O.; Görgün, C.Z.; Hotamisligil, G.S. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science, 2006, 313(5790), 1137-1140.
[http://dx.doi.org/10.1126/science.1128294] [PMID: 16931765]
[54]
Xiao, C.; Giacca, A.; Lewis, G.F. Sodium phenylbutyrate, a drug with known capacity to reduce endoplasmic reticulum stress, partially alleviates lipid-induced insulin resistance and beta-cell dysfunction in humans. Diabetes, 2011, 60(3), 918-924.
[http://dx.doi.org/10.2337/db10-1433] [PMID: 21270237]
[55]
Kars, M.; Yang, L.; Gregor, M.F.; Mohammed, B.S.; Pietka, T.A.; Finck, B.N.; Patterson, B.W.; Horton, J.D.; Mittendorfer, B.; Hotamisligil, G.S.; Klein, S. Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes, 2010, 59(8), 1899-1905.
[http://dx.doi.org/10.2337/db10-0308] [PMID: 20522594]
[56]
Jové, M.; Planavila, A.; Sánchez, R.M.; Merlos, M.; Laguna, J.C.; Vázquez-Carrera, M. Palmitate induces tumor necrosis factor-alpha expression in C2C12 skeletal muscle cells by a mechanism involving protein kinase C and nuclear factor-kappaB activation. Endocrinology, 2006, 147(1), 552-561.
[http://dx.doi.org/10.1210/en.2005-0440] [PMID: 16223857]
[57]
Tse, M.C.L.; Herlea-Pana, O.; Brobst, D.; Yang, X.; Wood, J.; Hu, X.; Liu, Z.; Lee, C.W.; Zaw, A.M.; Chow, B.K.C.; Ye, K.; Chan, C.B. Tumor necrosis factor-α promotes phosphoinositide 3-kinase enhancer A and AMP-activated protein kinase interaction to suppress lipid oxidation in skeletal muscle. Diabetes, 2017, 66(7), 1858-1870.
[http://dx.doi.org/10.2337/db16-0270] [PMID: 28404596]
[58]
Hu, P.; Han, Z.; Couvillon, A.D.; Kaufman, R.J.; Exton, J.H. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol. Cell. Biol., 2006, 26(8), 3071-3084.
[http://dx.doi.org/10.1128/MCB.26.8.3071-3084.2006] [PMID: 16581782]
[59]
American Diabetes Association. 6. Obesity management for the treatment of type 2 diabetes. Diabetes Care, 2016, 39(Suppl. 1), S47-S51.
[http://dx.doi.org/10.2337/dc16-S009] [PMID: 26696681]
[60]
Wing, R.R.; Lang, W.; Wadden, T.A.; Safford, M.; Knowler, W.C.; Bertoni, A.G.; Hill, J.O.; Brancati, F.L.; Peters, A.; Wagenknecht, L.; Look, A.R.G. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care, 2011, 34(7), 1481-1486.
[http://dx.doi.org/10.2337/dc10-2415] [PMID: 21593294]
[61]
Saltiel, A.R. New therapeutic approaches for the treatment of obesity. Sci. Transl. Med., 2016, 8(323)323rv2
[http://dx.doi.org/10.1126/scitranslmed.aad1811] [PMID: 26819198]
[62]
Adan, R.A. Mechanisms underlying current and future anti-obesity drugs. Trends Neurosci., 2013, 36(2), 133-140.
[http://dx.doi.org/10.1016/j.tins.2012.12.001] [PMID: 23312373]
[63]
Murray, S.; Tulloch, A.; Gold, M.S.; Avena, N.M. Hormonal and neural mechanisms of food reward, eating behaviour and obesity. Nat. Rev. Endocrinol., 2014, 10(9), 540-552.
[http://dx.doi.org/10.1038/nrendo.2014.91] [PMID: 24958311]
[64]
Huang, E.J.; Reichardt, L.F. Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci., 2001, 24, 677-736.
[http://dx.doi.org/10.1146/annurev.neuro.24.1.677] [PMID: 11520916]
[65]
Numakawa, T.; Suzuki, S.; Kumamaru, E.; Adachi, N.; Richards, M.; Kunugi, H. BDNF function and intracellular signaling in neurons. Histol. Histopathol., 2010, 25(2), 237-258.
[PMID: 20017110]
[66]
Pelleymounter, M.A.; Cullen, M.J.; Wellman, C.L. Characteristics of BDNF-induced weight loss. Exp. Neurol., 1995, 131(2), 229-238.
[http://dx.doi.org/10.1016/0014-4886(95)90045-4] [PMID: 7534721]
[67]
Gray, J.; Yeo, G.S.; Cox, J.J.; Morton, J.; Adlam, A.L.; Keogh, J.M.; Yanovski, J.A.; El Gharbawy, A.; Han, J.C.; Tung, Y.C.; Hodges, J.R.; Raymond, F.L.; O’rahilly, S.; Farooqi, I.S. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes, 2006, 55(12), 3366-3371.
[http://dx.doi.org/10.2337/db06-0550] [PMID: 17130481]
[68]
Yeo, G.S.; Connie Hung, C.C.; Rochford, J.; Keogh, J.; Gray, J.; Sivaramakrishnan, S.; O’Rahilly, S.; Farooqi, I.S. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat. Neurosci., 2004, 7(11), 1187-1189.
[http://dx.doi.org/10.1038/nn1336] [PMID: 15494731]
[69]
Unger, T.J.; Calderon, G.A.; Bradley, L.C.; Sena-Esteves, M.; Rios, M. Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J. Neurosci., 2007, 27(52), 14265-14274.
[http://dx.doi.org/10.1523/JNEUROSCI.3308-07.2007] [PMID: 18160634]
[70]
Meek, T.H.; Wisse, B.E.; Thaler, J.P.; Guyenet, S.J.; Matsen, M.E.; Fischer, J.D.; Taborsky, G.J. Jr.; Schwartz, M.W.; Morton, G.J. BDNF action in the brain attenuates diabetic hyperglycemia via insulin-independent inhibition of hepatic glucose production. Diabetes, 2013, 62(5), 1512-1518.
[http://dx.doi.org/10.2337/db12-0837] [PMID: 23274899]
[71]
Yamanaka, M.; Tsuchida, A.; Nakagawa, T.; Nonomura, T.; Ono-Kishino, M.; Sugaru, E.; Noguchi, H.; Taiji, M. Brain-derived neurotrophic factor enhances glucose utilization in peripheral tissues of diabetic mice. Diabetes Obes. Metab., 2007, 9(1), 59-64.
[http://dx.doi.org/10.1111/j.1463-1326.2006.00572.x] [PMID: 17199719]
[72]
Tsuchida, A.; Nakagawa, T.; Itakura, Y.; Ichihara, J.; Ogawa, W.; Kasuga, M.; Taiji, M.; Noguchi, H. The effects of brain-derived neurotrophic factor on insulin signal transduction in the liver of diabetic mice. Diabetologia, 2001, 44(5), 555-566.
[http://dx.doi.org/10.1007/s001250051661] [PMID: 11380073]
[73]
Fujinami, A.; Ohta, K.; Obayashi, H.; Fukui, M.; Hasegawa, G.; Nakamura, N.; Kozai, H.; Imai, S.; Ohta, M. Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance. Clin. Biochem., 2008, 41(10-11), 812-817.
[http://dx.doi.org/10.1016/j.clinbiochem.2008.03.003] [PMID: 18402781]
[74]
Krabbe, K.S.; Nielsen, A.R.; Krogh-Madsen, R.; Plomgaard, P.; Rasmussen, P.; Erikstrup, C.; Fischer, C.P.; Lindegaard, B.; Petersen, A.M.; Taudorf, S.; Secher, N.H.; Pilegaard, H.; Bruunsgaard, H.; Pedersen, B.K. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia, 2007, 50(2), 431-438.
[http://dx.doi.org/10.1007/s00125-006-0537-4] [PMID: 17151862]
[75]
Liu, W.; Han, X.; Zhou, X.; Zhang, S.; Cai, X.; Zhang, L.; Li, Y.; Li, M.; Gong, S.; Ji, L. Brain derived neurotrophic factor in newly diagnosed diabetes and prediabetes. Mol. Cell. Endocrinol., 2016, 429, 106-113.
[http://dx.doi.org/10.1016/j.mce.2016.04.002] [PMID: 27062899]
[76]
Shimoke, K.; Utsumi, T.; Kishi, S.; Nishimura, M.; Sasaya, H.; Kudo, M.; Ikeuchi, T. Prevention of endoplasmic reticulum stress-induced cell death by brain-derived neurotrophic factor in cultured cerebral cortical neurons. Brain Res., 2004, 1028(1), 105-111.
[http://dx.doi.org/10.1016/j.brainres.2004.09.005] [PMID: 15518647]
[77]
Matthews, V.B.; Aström, M.B.; Chan, M.H.; Bruce, C.R.; Krabbe, K.S.; Prelovsek, O.; Akerström, T.; Yfanti, C.; Broholm, C.; Mortensen, O.H.; Penkowa, M.; Hojman, P.; Zankari, A.; Watt, M.J.; Bruunsgaard, H.; Pedersen, B.K.; Febbraio, M.A. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia, 2009, 52(7), 1409-1418.
[http://dx.doi.org/10.1007/s00125-009-1364-1] [PMID: 19387610]
[78]
Genzer, Y.; Chapnik, N.; Froy, O. Effect of brain-derived neurotrophic factor (BDNF) on hepatocyte metabolism. Int. J. Biochem. Cell Biol., 2017, 88, 69-74.
[http://dx.doi.org/10.1016/j.biocel.2017.05.008] [PMID: 28483667]
[79]
Hristova, M.G. Metabolic syndrome--from the neurotrophic hypothesis to a theory. Med. Hypotheses, 2013, 81(4), 627-634.
[http://dx.doi.org/10.1016/j.mehy.2013.07.018] [PMID: 23899630]
[80]
Poduslo, J.F.; Curran, G.L. Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res. Mol. Brain Res., 1996, 36(2), 280-286.
[http://dx.doi.org/10.1016/0169-328X(95)00250-V] [PMID: 8965648]
[81]
Nagahara, A.H.; Tuszynski, M.H. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat. Rev. Drug Discov., 2011, 10(3), 209-219.
[http://dx.doi.org/10.1038/nrd3366] [PMID: 21358740]
[82]
Ibáñez, C.F. Neurotrophic factors: from structure-function studies to designing effective therapeutics. Trends Biotechnol., 1995, 13(6), 217-227.
[http://dx.doi.org/10.1016/S0167-7799(00)88949-0] [PMID: 7598845]
[83]
O’Leary, P.D.; Hughes, R.A. Design of potent peptide mimetics of brain-derived neurotrophic factor. J. Biol. Chem., 2003, 278(28), 25738-25744.
[http://dx.doi.org/10.1074/jbc.M303209200] [PMID: 12730196]
[84]
Fletcher, J.M.; Hughes, R.A. Novel monocyclic and bicyclic loop mimetics of brain-derived neurotrophic factor. J. Pept. Sci., 2006, 12(8), 515-524.
[http://dx.doi.org/10.1002/psc.760] [PMID: 16680799]
[85]
Fletcher, J.L.; Wood, R.J.; Nguyen, J.; Norman, E.M.L.; Jun, C.M.K.; Prawdiuk, A.R.; Biemond, M.; Nguyen, H.T.H.; Northfield, S.E.; Hughes, R.A.; Gonsalvez, D.G.; Xiao, J.; Murray, S.S. Targeting TrkB with a brain-derived neurotrophic factor mimetic promotes myelin repair in the brain. J. Neurosci., 2018, 38(32), 7088-7099.
[http://dx.doi.org/10.1523/JNEUROSCI.0487-18.2018] [PMID: 29976621]
[86]
Gudasheva, T.A.; Povarnina, P.; Logvinov, I.O.; Antipova, T.A.; Seredenin, S.B. Mimetics of brain-derived neurotrophic factor loops 1 and 4 are active in a model of ischemic stroke in rats. Drug Des. Devel. Ther., 2016, 10, 3545-3553.
[http://dx.doi.org/10.2147/DDDT.S118768] [PMID: 27843294]
[87]
Gudasheva, T.A.; Tarasiuk, A.V.; Sazonova, N.M.; Povarnina, P.Y.; Antipova, T.A.; Seredenin, S.B. A novel dimeric dipeptide mimetic of the BDNF selectively activates the MAPK-Erk signaling pathway. Dokl. Biochem. Biophys., 2017, 476(1), 291-295.
[http://dx.doi.org/10.1134/S1607672917050027] [PMID: 29101742]
[88]
Tarasiuk, A.V.; Gudasheva, T.A.; Sazonova, N.M.; Antipov, P.I.; Kurilov, D.V.; Povarnina, P.Iu.; Logvinov, I.O.; Antipova, T.A.; Seredenin, S.B. Study of structure-activity relationship in series of Gsb-106 analogues-dipeptide mimetics of brain-derived neurotrophic factor. Bioorg. Khim., 2014, 40(2), 142-156.
[PMID: 25895333]
[89]
Ostrovskaya, R.U.; Yagubova, S.S.; Gudasheva, T.A.; Seredenin, S.B. Antidiabetic Properties of low-molecular-weight BDNF mimetics depend on the type of activation of post-receptor signaling pathways. Bull. Exp. Biol. Med., 2018, 164(6), 734-737.
[http://dx.doi.org/10.1007/s10517-018-4069-y] [PMID: 29658083]
[90]
Bathina, S.; Srinivas, N.; Das, U.N. BDNF protects pancreatic β cells (RIN5F) against cytotoxic action of alloxan, streptozotocin, doxorubicin and benzo(a)pyrene in vitro. Metabolism, 2016, 65(5), 667-684.
[http://dx.doi.org/10.1016/j.metabol.2016.01.016] [PMID: 27085775]
[91]
Massa, S.M.; Yang, T.; Xie, Y.; Shi, J.; Bilgen, M.; Joyce, J.N.; Nehama, D.; Rajadas, J.; Longo, F.M. Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. J. Clin. Invest., 2010, 120(5), 1774-1785.
[http://dx.doi.org/10.1172/JCI41356] [PMID: 20407211]
[92]
Simmons, D.A.; Belichenko, N.P.; Yang, T.; Condon, C.; Monbureau, M.; Shamloo, M.; Jing, D.; Massa, S.M.; Longo, F.M. A small molecule TrkB ligand reduces motor impairment and neuropathology in R6/2 and BACHD mouse models of Huntington’s disease. J. Neurosci., 2013, 33(48), 18712-18727.
[http://dx.doi.org/10.1523/JNEUROSCI.1310-13.2013] [PMID: 24285878]
[93]
Han, J.; Pollak, J.; Yang, T.; Siddiqui, M.R.; Doyle, K.P.; Taravosh-Lahn, K.; Cekanaviciute, E.; Han, A.; Goodman, J.Z.; Jones, B.; Jing, D.; Massa, S.M.; Longo, F.M.; Buckwalter, M.S. Delayed administration of a small molecule tropomyosin-related kinase B ligand promotes recovery after hypoxic-ischemic stroke. Stroke, 2012, 43(7), 1918-1924.
[http://dx.doi.org/10.1161/STROKEAHA.111.641878] [PMID: 22535263]
[94]
Li, W.; Bellot-Saez, A.; Phillips, M.L.; Yang, T.; Longo, F.M.; Pozzo-Miller, L. A small-molecule TrkB ligand restores hippocampal synaptic plasticity and object location memory in Rett syndrome mice. Dis. Model. Mech., 2017, 10(7), 837-845.
[http://dx.doi.org/10.1242/dmm.029959] [PMID: 28679669]
[95]
Jang, S.W.; Liu, X.; Yepes, M.; Shepherd, K.R.; Miller, G.W.; Liu, Y.; Wilson, W.D.; Xiao, G.; Blanchi, B.; Sun, Y.E.; Ye, K. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc. Natl. Acad. Sci. USA, 2010, 107(6), 2687-2692.
[http://dx.doi.org/10.1073/pnas.0913572107] [PMID: 20133810]
[96]
Liu, C.; Chan, C.B.; Ye, K. 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. Transl. Neurodegener., 2016, 5, 2.
[http://dx.doi.org/10.1186/s40035-015-0048-7] [PMID: 26740873]
[97]
Arevalo, J.C.; Conde, B.; Hempstead, B.L.; Chao, M.V.; Martin-Zanca, D.; Perez, P. TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of the receptor. Mol. Cell. Biol., 2000, 20(16), 5908-5916.
[http://dx.doi.org/10.1128/MCB.20.16.5908-5916.2000] [PMID: 10913174]
[98]
Sakane, T.; Pardridge, W.M. Carboxyl-directed pegylation of brain-derived neurotrophic factor markedly reduces systemic clearance with minimal loss of biologic activity. Pharm. Res., 1997, 14(8), 1085-1091.
[http://dx.doi.org/10.1023/A:1012117815460] [PMID: 9279893]
[99]
Liu, X.; Qi, Q.; Xiao, G.; Li, J.; Luo, H.R.; Ye, K. O-methylated metabolite of 7,8-dihydroxyflavone activates TrkB receptor and displays antidepressant activity. Pharmacology, 2013, 91(3-4), 185-200.
[http://dx.doi.org/10.1159/000346920] [PMID: 23445871]
[100]
Chan, C.B.; Tse, M.C.; Liu, X.; Zhang, S.; Schmidt, R.; Otten, R.; Liu, L.; Ye, K. Activation of muscular TrkB by its small molecular agonist 7,8-dihydroxyflavone sex-dependently regulates energy metabolism in diet-induced obese mice. Chem. Biol., 2015, 22(3), 355-368.
[http://dx.doi.org/10.1016/j.chembiol.2015.02.003] [PMID: 25754472]
[101]
Wood, J.; Tse, M.C.L.; Yang, X.; Brobst, D.; Liu, Z.; Pang, B.P.S.; Chan, W.S.; Zaw, A.M.; Chow, B.K.C.; Ye, K.; Lee, C.W.; Chan, C.B. BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle. Metabolism, 2018, 87, 113-122.
[http://dx.doi.org/10.1016/j.metabol.2018.06.007] [PMID: 29935237]
[102]
Liu, X.; Obianyo, O.; Chan, C.B.; Huang, J.; Xue, S.; Yang, J.J.; Zeng, F.; Goodman, M.; Ye, K. Biochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the TrkB receptor. J. Biol. Chem., 2014, 289(40), 27571-27584.
[http://dx.doi.org/10.1074/jbc.M114.562561] [PMID: 25143381]
[103]
Jin, H.; Zhu, Y.; Li, Y.; Ding, X.; Ma, W.; Han, X.; Wang, B. BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury. Apoptosis, 2019, 24(5-6), 511-528.
[http://dx.doi.org/10.1007/s10495-019-01535-x] [PMID: 30877409]
[104]
Yang, X.; Brobst, D.; Chan, W.S.; Tse, M.C.L.; Herlea-Pana, O.; Ahuja, P.; Bi, X.; Zaw, A.M.; Kwong, Z.S.W.; Jia, W.H.; Zhang, Z.G.; Zhang, N.; Chow, S.K.H.; Cheung, W.H.; Louie, J.C.Y.; Griffin, T.M.; Nong, W.; Hui, J.H.L.; Du, G.H.; Noh, H.L.; Saengnipanthkul, S.; Chow, B.K.C.; Kim, J.K.; Lee, C.W.; Chan, C.B. Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility. Sci. Signal., 2019, 12(594), 12.
[http://dx.doi.org/10.1126/scisignal.aau1468] [PMID: 31409756]
[105]
Liu, X.; Chan, C.B.; Jang, S.W.; Pradoldej, S.; Huang, J.; He, K.; Phun, L.H.; France, S.; Xiao, G.; Jia, Y.; Luo, H.R.; Ye, K. A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits potent antidepressant effect. J. Med. Chem., 2010, 53(23), 8274-8286.
[http://dx.doi.org/10.1021/jm101206p] [PMID: 21073191]
[106]
Liu, X.; Chan, C.B.; Qi, Q.; Xiao, G.; Luo, H.R.; He, X.; Ye, K. Optimization of a small tropomyosin-related kinase B (TrkB) agonist 7,8-dihydroxyflavone active in mouse models of depression. J. Med. Chem., 2012, 55(19), 8524-8537.
[http://dx.doi.org/10.1021/jm301099x] [PMID: 22984948]
[107]
Chen, C.; Wang, Z.; Zhang, Z.; Liu, X.; Kang, S.S.; Zhang, Y.; Ye, K. The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2018, 115(3), 578-583.
[http://dx.doi.org/10.1073/pnas.1718683115] [PMID: 29295929]
[108]
Rao, Y.K.; Lee, M.J.; Chen, K.; Lee, Y.C.; Wu, W.S.; Tzeng, Y.M. Insulin-mimetic action of rhoifolin and cosmosiin isolated from Citrus grandis (L.) osbeck leaves: enhanced adiponectin secretion and insulin receptor phosphorylation in 3T3-L1 cells. Evid. Based Complement. Alternat. Med., 2011, 20116, 24375.
[http://dx.doi.org/10.1093/ecam/nep204] [PMID: 20008903]
[109]
Temple, R.C.; Carrington, C.A.; Luzio, S.D.; Owens, D.R.; Schneider, A.E.; Sobey, W.J.; Hales, C.N. Insulin deficiency in non-insulin-dependent diabetes. Lancet, 1989, 1(8633), 293-295.
[http://dx.doi.org/10.1016/S0140-6736(89)91306-8] [PMID: 2563455]
[110]
Richardson, T.; Kerr, D. Skin-related complications of insulin therapy: epidemiology and emerging management strategies. Am. J. Clin. Dermatol., 2003, 4(10), 661-667.
[http://dx.doi.org/10.2165/00128071-200304100-00001] [PMID: 14507228]
[111]
Zhang, B.; Salituro, G.; Szalkowski, D.; Li, Z.; Zhang, Y.; Royo, I.; Vilella, D.; Díez, M.T.; Pelaez, F.; Ruby, C.; Kendall, R.L.; Mao, X.; Griffin, P.; Calaycay, J.; Zierath, J.R.; Heck, J.V.; Smith, R.G.; Moller, D.E. Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science, 1999, 284(5416), 974-977.
[http://dx.doi.org/10.1126/science.284.5416.974] [PMID: 10320380]
[112]
Roper, M.G.; Qian, W.J.; Zhang, B.B.; Kulkarni, R.N.; Kahn, C.R.; Kennedy, R.T. Effect of the insulin mimetic L-783,281 on intracellular Ca2+ and insulin secretion from pancreatic beta-cells. Diabetes, 2002, 51(Suppl. 1), S43-S49.
[http://dx.doi.org/10.2337/diabetes.51.2007.S43] [PMID: 11815457]
[113]
Velliquette, R.A.; Friedman, J.E.; Shao, J.; Zhang, B.B.; Ernsberger, P. Therapeutic actions of an insulin receptor activator and a novel peroxisome proliferator-activated receptor gamma agonist in the spontaneously hypertensive obese rat model of metabolic syndrome X. J. Pharmacol. Exp. Ther., 2005, 314(1), 422-430.
[http://dx.doi.org/10.1124/jpet.104.080606] [PMID: 15833894]
[114]
Shah, D.I.; Singh, M. Effect of demethylasterriquinone b1 in hypertension associated vascular endothelial dysfunction. Int. J. Cardiol., 2007, 120(3), 317-324.
[http://dx.doi.org/10.1016/j.ijcard.2006.10.006] [PMID: 17240464]
[115]
Wood, H.B., Jr; Black, R.; Salituro, G.; Szalkowski, D.; Li, Z.; Zhang, Y.; Moller, D.E.; Zhang, B.; Jones, A.B. The basal SAR of a novel insulin receptor activator. Bioorg. Med. Chem. Lett., 2000, 10(11), 1189-1192.
[http://dx.doi.org/10.1016/S0960-894X(00)00206-7] [PMID: 10866378]
[116]
Lin, B.; Li, Z.; Park, K.; Deng, L.; Pai, A.; Zhong, L.; Pirrung, M.C.; Webster, N.J. Identification of novel orally available small molecule insulin mimetics. J. Pharmacol. Exp. Ther., 2007, 323(2), 579-585.
[http://dx.doi.org/10.1124/jpet.107.126102] [PMID: 17687071]
[117]
Liu, K.; Xu, L.; Szalkowski, D.; Li, Z.; Ding, V.; Kwei, G.; Huskey, S.; Moller, D.E.; Heck, J.V.; Zhang, B.B.; Jones, A.B. Discovery of a potent, highly selective, and orally efficacious small-molecule activator of the insulin receptor. J. Med. Chem., 2000, 43(19), 3487-3494.
[http://dx.doi.org/10.1021/jm000285q] [PMID: 11000003]
[118]
Ding, V.D.; Qureshi, S.A.; Szalkowski, D.; Li, Z.; Biazzo-Ashnault, D.E.; Xie, D.; Liu, K.; Jones, A.B.; Moller, D.E.; Zhang, B.B. Regulation of insulin signal transduction pathway by a small-molecule insulin receptor activator. Biochem. J., 2002, 367(Pt 1), 301-306.
[http://dx.doi.org/10.1042/bj20020708] [PMID: 12036431]
[119]
Tsai, H.J.; Chou, S.Y. A novel hydroxyfuroic acid compound as an insulin receptor activator. Structure and activity relationship of a prenylindole moiety to insulin receptor activation. J. Biomed. Sci., 2009, 16, 68.
[http://dx.doi.org/10.1186/1423-0127-16-68] [PMID: 19642985]
[120]
Benter, I.F.; Yousif, M.H.; Hollins, A.J.; Griffiths, S.M.; Akhtar, S. Diabetes-induced renal vascular dysfunction is normalized by inhibition of epidermal growth factor receptor tyrosine kinase. J. Vasc. Res., 2005, 42(4), 284-291.
[http://dx.doi.org/10.1159/000085904] [PMID: 15915001]
[121]
Benter, I.F.; Yousif, M.H.; Griffiths, S.M.; Benboubetra, M.; Akhtar, S. Epidermal growth factor receptor tyrosine kinase-mediated signalling contributes to diabetes-induced vascular dysfunction in the mesenteric bed. Br. J. Pharmacol., 2005, 145(6), 829-836.
[http://dx.doi.org/10.1038/sj.bjp.0706238] [PMID: 15852031]
[122]
He, K.; Chan, C.B.; Liu, X.; Jia, Y.; Luo, H.R.; France, S.A.; Liu, Y.; Wilson, W.D.; Ye, K. Identification of a molecular activator for insulin receptor with potent anti-diabetic effects. J. Biol. Chem., 2011, 286(43), 37379-37388.
[http://dx.doi.org/10.1074/jbc.M111.247387] [PMID: 21908618]
[123]
Manchem, V.P.; Goldfine, I.D.; Kohanski, R.A.; Cristobal, C.P.; Lum, R.T.; Schow, S.R.; Shi, S.; Spevak, W.R.; Laborde, E.; Toavs, D.K.; Villar, H.O.; Wick, M.M.; Kozlowski, M.R. A novel small molecule that directly sensitizes the insulin receptor in vitro and in vivo. Diabetes, 2001, 50(4), 824-830.
[http://dx.doi.org/10.2337/diabetes.50.4.824] [PMID: 11289048]
[124]
Pender, C.; Goldfine, I.D.; Manchem, V.P.; Evans, J.L.; Spevak, W.R.; Shi, S.; Rao, S.; Bajjalieh, S.; Maddux, B.A.; Youngren, J.F. Regulation of insulin receptor function by a small molecule insulin receptor activator. J. Biol. Chem., 2002, 277(46), 43565-43571.
[http://dx.doi.org/10.1074/jbc.M202426200] [PMID: 12213804]
[125]
Cheng, M.; Chen, S.; Schow, S.R.; Manchem, V.P.; Spevak, W.R.; Cristobal, C.P.; Shi, S.; Macsata, R.W.; Lum, R.T.; Goldfine, I.D.; Keck, J.G. In vitro and in vivo prevention of HIV protease inhibitor-induced insulin resistance by a novel small molecule insulin receptor activator. J. Cell. Biochem., 2004, 92(6), 1234-1245.
[http://dx.doi.org/10.1002/jcb.20150] [PMID: 15258906]
[126]
Plosker, G.L.; Noble, S. Indinavir: a review of its use in the management of HIV infection. Drugs, 1999, 58(6), 1165-1203.
[http://dx.doi.org/10.2165/00003495-199958060-00011] [PMID: 10651394]
[127]
Wu, M.; Dai, G.; Yao, J.; Hoyt, S.; Wang, L.; Mu, J. Potentiation of insulin-mediated glucose lowering without elevated hypoglycemia risk by a small molecule insulin receptor modulator. PLoS One, 2015, 10(3)e0122012
[http://dx.doi.org/10.1371/journal.pone.0122012] [PMID: 25799496]
[128]
Qiang, G.; Xue, S.; Yang, J.J.; Du, G.; Pang, X.; Li, X.; Goswami, D.; Griffin, P.R.; Ortlund, E.A.; Chan, C.B.; Ye, K. Identification of a small molecular insulin receptor agonist with potent antidiabetes activity. Diabetes, 2014, 63(4), 1394-1409.
[http://dx.doi.org/10.2337/db13-0334] [PMID: 24651808]
[129]
Li, Y.; Kim, J.; Li, J.; Liu, F.; Liu, X.; Himmeldirk, K.; Ren, Y.; Wagner, T.E.; Chen, X. Natural anti-diabetic compound 1,2,3,4,6-penta-O-galloyl-D-glucopyranose binds to insulin receptor and activates insulin-mediated glucose transport signaling pathway. Biochem. Biophys. Res. Commun., 2005, 336(2), 430-437.
[http://dx.doi.org/10.1016/j.bbrc.2005.08.103] [PMID: 16137651]
[130]
Cao, Y.; Li, Y.; Kim, J.; Ren, Y.; Himmeldirk, K.; Liu, Y.; Qian, Y.; Liu, F.; Chen, X. Orally efficacious novel small molecule 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl-α-D-glucopyranose selectively and potently stimulates insulin receptor and alleviates diabetes. J. Mol. Endocrinol., 2013, 51(1), 15-26.
[http://dx.doi.org/10.1530/JME-12-0171] [PMID: 23549408]
[131]
Mukherjee, S.; Chattopadhyay, M.; Bhattacharya, S.; Dasgupta, S.; Hussain, S.; Bharadwaj, S.K.; Talukdar, D.; Usmani, A.; Pradhan, B.S.; Majumdar, S.S.; Chattopadhyay, P.; Mukhopadhyay, S.; Maity, T.K.; Chaudhuri, M.K.; Bhattacharya, S. A small insulinomimetic molecule also improves insulin sensitivity in diabetic mice. PLoS One, 2017, 12(1)e0169809
[http://dx.doi.org/10.1371/journal.pone.0169809] [PMID: 28072841]
[132]
Shechter, Y.; Karlish, S.J. Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature, 1980, 284(5756), 556-558.
[http://dx.doi.org/10.1038/284556a0] [PMID: 6988725]
[133]
Thompson, K.H.; McNeill, J.H.; Orvig, C. Vanadium compounds as insulin mimics. Chem. Rev., 1999, 99(9), 2561-2572.
[http://dx.doi.org/10.1021/cr980427c] [PMID: 11749492]
[134]
Bellomo, E.; Birla Singh, K.; Massarotti, A.; Hogstrand, C.; Maret, W. The metal face of protein tyrosine phosphatase 1B. Coord. Chem. Rev., 2016, 327-328, 70-83.
[http://dx.doi.org/10.1016/j.ccr.2016.07.002] [PMID: 27890939]
[135]
García-Vicente, S.; Yraola, F.; Marti, L.; González-Muñoz, E.; García-Barrado, M.J.; Cantó, C.; Abella, A.; Bour, S.; Artuch, R.; Sierra, C.; Brandi, N.; Carpéné, C.; Moratinos, J.; Camps, M.; Palacín, M.; Testar, X.; Gumà, A.; Albericio, F.; Royo, M.; Mian, A.; Zorzano, A. Oral insulin-mimetic compounds that act independently of insulin. Diabetes, 2007, 56(2), 486-493.
[http://dx.doi.org/10.2337/db06-0269] [PMID: 17259395]
[136]
Cohen, N.; Halberstam, M.; Shlimovich, P.; Chang, C.J.; Shamoon, H.; Rossetti, L. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. J. Clin. Invest., 1995, 95(6), 2501-2509.
[http://dx.doi.org/10.1172/JCI117951] [PMID: 7769096]

Rights & Permissions Print Cite
Article Metrics
51
2
© 2024 Bentham Science Publishers | Privacy Policy