Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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

Beneficial Effects of PIN1 Inhibition on Diabetes Mellitus: A Concise Review

In Press, (this is not the final "Version of Record"). Available online 30 April, 2024
Author(s): Meeramol C. Chellappan, Soumya Vasu*, Shriraam Mahadevan, Muthu Kumaradoss Kathiravan, Saravanan Jayaraman and Soniya Naik
Published on: 30 April, 2024

DOI: 10.2174/0118715303297663240307060019

Price: $95

Abstract

Type 2 diabetes mellitus is a long-term medical illness in which the body either becomes resistant to insulin or fails to produce it sufficiently. Mostly, combinatorial therapy is required to control blood glucose levels. However, combinatorial therapy has detrimental side effects. The prevalence of the cases and subsequent increases in medical costs of the same intimidate human health globally. While there have been a lot of studies focused on developing diabetic regimens that work to lower blood glucose levels, their effectiveness is short-lived because of unfavorable side effects, such as weight gain and hypoglycemia. In recent years, the PIN1 (protein interacting with NIMA) enzyme has attracted the attention of researchers. Previous studies suggested that PIN1 may act on the various substrates that are involved in the progression of T2DM and also help in the management of diabetes-related disorders. Thus, the focus of the current review is to examine the correlation between PIN1, T2DM and its related disorders and explore the possibility of developing novel therapeutic targets through PIN1 inhibition.

[1]
Tahrani, A.A.; Bailey, C.J.; Del Prato, S.; Barnett, A.H. Management of type 2 diabetes: New and future developments in treatment. Lancet, 2011, 378(9786), 182-197.
[http://dx.doi.org/10.1016/S0140-6736(11)60207-9] [PMID: 21705062]
[2]
Zheng, Y.; Ley, S.H.; Hu, F.B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol., 2018, 14(2), 88-98.
[PMID: 29219149]
[3]
Kerru, N.; Singh-Pillay, A.; Awolade, P.; Singh, P. Current anti-diabetic agents and their molecular targets: A review. Eur. J. Med. Chem., 2018, 152, 436-488.
[http://dx.doi.org/10.1016/j.ejmech.2018.04.061] [PMID: 29751237]
[4]
Guariguata, L.; Whiting, D.R.; Hambleton, I.; Beagley, J.; Linnenkamp, U.; Shaw, J.E. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res. Clin. Pract., 2014, 103(2), 137-149.
[http://dx.doi.org/10.1016/j.diabres.2013.11.002] [PMID: 24630390]
[5]
Belete, T.M. A recent achievement in the discovery and development of novel targets for the treatment of Type-2 Diabetes Mellitus. J. Exp. Pharmacol., 2020, 12, 1-15.
[http://dx.doi.org/10.2147/JEP.S226113] [PMID: 32021494]
[6]
DeFronzo, R.A.; Triplitt, C.L.; Abdul-Ghani, M.; Cersosimo, E. Novel agents for the treatment of Type 2 Diabetes. Diabetes Spectr., 2014, 27(2), 100-112.
[http://dx.doi.org/10.2337/diaspect.27.2.100] [PMID: 26246766]
[7]
Danaei, G.; Finucane, M.M.; Lu, Y.; Singh, G.M.; Cowan, M.J.; Paciorek, C.J.; Lin, J.K.; Farzadfar, F.; Khang, Y.H.; Stevens, G.A.; Rao, M.; Ali, M.K.; Riley, L.M.; Robinson, C.A.; Ezzati, M. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet, 2011, 378(9785), 31-40.
[http://dx.doi.org/10.1016/S0140-6736(11)60679-X] [PMID: 21705069]
[8]
Safarkhani, M.; Aldhaher, A.; Heidari, G.; Zare, E.N.; Warkiani, M.E.; Akhavan, O.; Huh, Y.; Rabiee, N. Nanomaterial-assisted wearable glucose biosensors for noninvasive real-time monitoring: Pioneering point-of-care and beyond. Nano Mater. Sci., 2024, 6(3), 263-283.
[9]
Coughlan, K.A.; Valentine, R.J.; Ruderman, N.B.; Saha, A.K. AMPK activation: A therapeutic target for type 2 diabetes? Diabetes Metab. Syndr. Obes., 2014, 7, 241-253.
[PMID: 25018645]
[10]
Nakatsu, Y.; Matsunaga, Y.; Yamamotoya, T.; Ueda, K.; Inoue, Y.; Mori, K.; Sakoda, H.; Fujishiro, M.; Ono, H.; Kushiyama, A.; Asano, T. Physiological and pathogenic roles of prolyl isomerase pin1 in metabolic regulations via multiple signal transduction pathway modulations. Int. J. Mol. Sci., 2016, 17(9), 1495.
[http://dx.doi.org/10.3390/ijms17091495] [PMID: 27618008]
[11]
Andreotti, A.H. Native state proline isomerization: An intrinsic molecular switch. Biochemistry, 2003, 42(32), 9515-9524.
[http://dx.doi.org/10.1021/bi0350710] [PMID: 12911293]
[12]
Lu, K.P.; Zhou, X.Z. The prolyl isomerase PIN1: A pivotal new twist in phosphorylation signalling and disease. Nat. Rev. Mol. Cell Biol., 2007, 8(11), 904-916.
[http://dx.doi.org/10.1038/nrm2261] [PMID: 17878917]
[13]
He, S.; Li, L.; Jin, R.; Lu, X. Biological function of Pin1 in vivo and its inhibitors for preclinical study: Early development, current strategies, and future directions. J. Med. Chem., 2023, 66(14), 9251-9277.
[http://dx.doi.org/10.1021/acs.jmedchem.3c00390] [PMID: 37438908]
[14]
Min, S.H.; Zhou, X.Z.; Lu, K.P. The role of Pin1 in the development and treatment of cancer. Arch. Pharm. Res., 2016, 39(12), 1609-1620.
[http://dx.doi.org/10.1007/s12272-016-0821-x] [PMID: 27572155]
[15]
Choi, H.J.; Kim, J.Y.; Lim, S-C.; Kim, G.; Yun, H.J.; Choi, H.S. Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression. Br. J. Pharmacol., 2015, 172(21), 5096-5109.
[http://dx.doi.org/10.1111/bph.13274] [PMID: 26267432]
[16]
Chen, Y.; Wu, Y.; Yang, H.; Li, X.; Jie, M.; Hu, C.; Wu, Y.; Yang, S.; Yang, Y. Prolyl isomerase Pin1: A promoter of cancer and a target for therapy. Cell Death Dis., 2018, 9(9), 883.
[http://dx.doi.org/10.1038/s41419-018-0844-y] [PMID: 30158600]
[17]
Chuang, H.H.; Zhen, Y.Y.; Tsai, Y.C.; Chuang, C.H.; Huang, M.S.; Hsiao, M.; Yang, C.J. Targeting Pin1 for Modulation of cell motility and cancer therapy. Biomedicines, 2021, 9(4), 359.
[http://dx.doi.org/10.3390/biomedicines9040359] [PMID: 33807199]
[18]
Mihaylova, M.M.; Shaw, R.J. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol., 2011, 13(9), 1016-1023.
[http://dx.doi.org/10.1038/ncb2329] [PMID: 21892142]
[19]
Almasi, F.; Mohammadipanah, F. Prominent and emerging anti-diabetic molecular targets. J. Drug Target., 2021, 29(5), 491-506.
[http://dx.doi.org/10.1080/1061186X.2020.1859517] [PMID: 33336602]
[20]
Nakatsu, Y.; Iwashita, M.; Sakoda, H.; Ono, H.; Nagata, K.; Matsunaga, Y.; Fukushima, T.; Fujishiro, M.; Kushiyama, A.; Kamata, H.; Takahashi, S.I.; Katagiri, H.; Honda, H.; Kiyonari, H.; Uchida, T.; Asano, T. Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the γ subunit. J. Biol. Chem., 2015, 290(40), 24255-24266.
[http://dx.doi.org/10.1074/jbc.M115.658559] [PMID: 26276391]
[21]
Aldhaher, A.; Safarkhani, M. Possible involvement of normalized PIN1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice. Diabetol. Metabol. Syndr., 2019, 11(1), 57.
[22]
Choi, H.M. Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression. British. J. Pharmacol., 2015, 172(21), 5096-5109.
[23]
Arguello, D.; P. D. H. B. L. M. M. G. E.-L. M., Thomas, K.S. “ HHS Public Access,” Physiol. Behav., 2017, 176(1), 139-148.
[http://dx.doi.org/10.1016/j.envres.2015.06.002.Maternal]
[24]
Qiu, J.; Yang, R.; Tang, Y.; Lin, Y.; Xu, H.; Zhang, N.; Liang, M.; Cai, H.; Zeng, K.; Wu, X. BRD4 and PIN1 gene polymorphisms are associated with high pulse pressure risk in a southeastern Chinese population. BMC Cardiovasc. Disord., 2020, 20(1), 475.
[http://dx.doi.org/10.1186/s12872-020-01757-x] [PMID: 33148187]
[25]
Yu, J.; Hu, D.; Wang, L.; Fan, Z.; Xu, C.; Lin, Y.; Chen, X.; Lin, J.; Peng, F. Hyperglycemia induces gastric carcinoma proliferation and migration via the Pin1/BRD4 pathway. Cell Death Discov., 2022, 8(1), 224.
[http://dx.doi.org/10.1038/s41420-022-01030-4] [PMID: 35461311]
[26]
Liu, X.; Liang, E.; Song, X.; Du, Z.; Zhang, Y.; Zhao, Y. Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice. Biochem. Biophys. Res. Commun., 2016, 479(1), 109-115.
[http://dx.doi.org/10.1016/j.bbrc.2016.09.050] [PMID: 27634219]
[27]
Wang, X.; Li, M.; Chen, S.; Li, S.; Guo, F. PIN1 facilitates isoproterenol-induced cardiac fibrosis and collagen deposition by promoting oxidative stress and activating the MEK1/2-ERK1/2 signal transduction pathway in rats. Int. J. Mol. Med., 2017.
[28]
Lv, L.; Zhang, J.; Zhang, L.; Xue, G.; Wang, P.; Meng, Q.; Liang, W. Essential role of Pin1 via STAT 3 signalling and mitochondria‐dependent pathways in restenosis in type 2 diabetes. J. Cell. Mol. Med., 2013, 17(8), 989-1005.
[http://dx.doi.org/10.1111/jcmm.12082] [PMID: 23750710]
[29]
Paneni, F.; Costantino, S.; Castello, L.; Battista, R.; Capretti, G.; Chiandotto, S.; D’Amario, D.; Scavone, G.; Villano, A.; Rustighi, A.; Crea, F.; Pitocco, D.; Lanza, G.; Volpe, M.; Del Sal, G.; Lüscher, T.F.; Cosentino, F. Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: Insights in patients with diabetes. Eur. Heart J., 2015, 36(13), 817-828.
[http://dx.doi.org/10.1093/eurheartj/ehu179] [PMID: 24801072]
[30]
Fagiani, F.; Vlachou, M.; Di Marino, D.; Canobbio, I.; Romagnoli, A.; Racchi, M.; Govoni, S.; Lanni, C. Pin1 as molecular switch in vascular endothelium: notes on its putative role in age-associated vascular diseases. Cells, 2021, 10(12), 3287-7.
[http://dx.doi.org/10.3390/cells10123287] [PMID: 34943794]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy