Role of Glycogen synthase kinase-3 in the etiology of Type 2 Diabetes Mellitus: A review

: The risk of type 2 diabetes mellitus (T2DM) is increasing abundantly due to lifestyle-related obesity and associated cardiovascular problems. Presently, Glycogen synthase kinase-3 (GSK-3) has gained considerable attention from biomedical scientists to treat diabetes. Phosphorylation of GSK-3 permits a number of cellular activities like regulation of cell signaling, cellular metabolism, cell proliferation and cellular transport. Inhibiting GSK-3 activity by pharmacological intervention has become an important strategy for the management of T2DM. This review focuses on the schematic representation of fundamental GSK-3 enzymology and encompasses the GSK-3 inhibitors as a future therapeutic lead target for the management of T2DM that may significantly regulate insulin sensitivity to insulin receptor, glycogen synthesis and glucose metabolism. The various signaling mechanisms of inhibiting the GSK-3 by describing insulin signaling through Insulin Receptor Substrate (IRS-1), Phosphatidylinositol-3 Kinase (PI3K) and Protein Kinase B (PKB/ AKT) pathways that may hopefully facilitate the pharmacologist to design for antidiabetic drug evaluation model in near future have also been highlighted.

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Glycogen Synthase Kinase-3β Is Associated with the Prognosis of Hepatocellular Carcinoma and May Mediate the Influence of Type 2 Diabetes Mellitus on Hepatocellular Carcinoma

PLoS ONE ◽

10.1371/journal.pone.0105624 ◽

2014 ◽

Vol 9 (8) ◽

pp. e105624 ◽

Cited By ~ 8

Author(s):

Guoliang Qiao ◽

Yuan Le ◽

Jun Li ◽

Lianghuan Wang ◽

Feng Shen

Keyword(s):

Diabetes Mellitus ◽

Hepatocellular Carcinoma ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycogen Synthase ◽

Glycogen Synthase Kinase ◽

Glycogen Synthase Kinase 3Β

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Molecular docking analysis of compounds from Justica adhatoda L with glycogen synthase kinase-3 β

Bioinformation ◽

10.6026/97320630016893 ◽

2020 ◽

Vol 16 (11) ◽

pp. 893-899

Author(s):

Selvaraj Jayaraman ◽

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Molecular Docking ◽

Glycogen Synthase ◽

Analysis Data ◽

Glycogen Synthase Kinase ◽

Glycogen Synthase Kinase 3 ◽

Docking Analysis ◽

Molecular Docking Analysis

Type 2 diabetes mellitus (T2DM) is linked with Glycogen synthase kinase-3 β.Therefore, it is ofinterest to document molecular docking analysis data of compounds from Justica adhatoda L with glycogen synthase kinase-3 β. We report the binding features of ethambutol, pyrazinamide, stigmasterol and vasicoline with GSK-3 β.

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Echinops Spp. Polysaccharide B Ameliorates Metabolic Abnormalities in a Rat Model of Type 2 Diabetes Mellitus

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:106-114 ◽

2020 ◽

Vol 19 (1) ◽

pp. 106-114

Author(s):

Guang Hao ◽

Xiaoyu Ma ◽

Mengru Jiang ◽

Zhenzhen Gao ◽

Ying Yang

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Secretion ◽

Insulin Receptor ◽

Skeletal Muscles ◽

Insulin Receptor Substrate ◽

Sprague Dawley

This study examined the in vivo effects of Echinops spp. polysaccharide B on type 2 diabetes mellitus in Sprague-Dawley rats. We constructed a type 2 diabetes mellitus Sprague-Dawley rat models by feeding a high-fat and high-sugar diet plus intraperitoneal injection of a small dose of streptozotocin. Using this diabetic rat model, different doses of Echinops polysaccharide B were administered orally for seven weeks. Groups receiving Xiaoke pill and metformin served as positive controls. The results showed that Echinops polysaccharide B treatment normalized the weight and blood sugar levels in the type 2 diabetes mellitus rats, increased muscle and liver glycogen content, improved glucose tolerance, increased insulin secretion, and reduced glucagon and insulin resistance indices. More importantly, Echinops polysaccharide B treatment upregulated the expression of insulin receptor in the liver, skeletal muscles, and pancreas, and significantly improved the expression levels of insulin receptor substrate-2 protein in the liver and pancreas, as well as it increased insulin receptor substrate-1 expression in skeletal muscles. These two proteins play crucial roles in increasing insulin secretion and in controlling type 2 diabetes mellitus. The findings of the present study suggest that Echinops polysaccharide B could improve the status of diabetes in type 2 diabetes mellitus rats, which may be achieved by improving insulin resistance. Our study provides a new insight into the development of a natural drug for the control of type 2 diabetes mellitus.

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Insulin receptor substrate polymorphisms and Type 2 diabetes mellitus

Pharmacogenomics ◽

10.1517/14622416.1.3.343 ◽

2000 ◽

Vol 1 (3) ◽

pp. 343-357 ◽

Cited By ~ 13

Author(s):

Giorgio Sesti

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Receptor ◽

Insulin Receptor Substrate

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Physical exercise prevents the development of type 2 diabetes mellitus in Psammomys obesus

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00296.2001 ◽

2002 ◽

Vol 282 (2) ◽

pp. E370-E375 ◽

Cited By ~ 11

Author(s):

Yuval Heled ◽

Yair Shapiro ◽

Yoav Shani ◽

Dani S. Moran ◽

Lea Langzam ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Exercise Training ◽

Insulin Receptor ◽

High Energy ◽

Serine Phosphorylation ◽

Psammomys Obesus ◽

Group Protein

We hypothesized that exercise training might prevent diabetes mellitus in Psammomys obesus. Animals were assigned to three groups: high-energy diet (CH), high-energy diet and exercise (EH), and low-energy diet (CL). The EH group ran on a treadmill 5 days/wk, twice a day. After 4 wk, 93% of the CH group were diabetic compared with only 20% of the EH group. There was no difference in weight gain among the groups. Both EH and CH groups were hyperinsulinemic. Epididymal fat (% of body weight) was higher in the CH group than in either the EH and or the CL group. Protein kinase C (PKC)-δ activity and serine phosphorylation were higher in the EH group. No differences were found in tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase among the groups. We demonstrate for the first time that exercise training effectively prevents the progression of diabetes mellitus type 2 in Psammomys obesus. PKC-δ may be involved in the adaptive effects of exercise in skeletal muscles that lead to the prevention of type 2 diabetes mellitus.

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