HD-6277, a Novel GPR40 Agonist, Improves Glucose Homeostasis and Enhanced Glucose-Dependent Insulin Secretion in Beta Cells and Type 2 Diabetic Rats

Diabetic patients are often treated with an ACEi (angiotensin-converting enzyme inhibitor) or angiotensin receptor antagonist against hypertension or albuminuria. These drugs also have a positive impact on glucose tolerance, but the mechanism for this remains elusive. Hypothesizing a positive non-additive effect, we studied whether the angiotensin receptor antagonist telmisartan or the ACEi ramipril acutely influence insulin secretion and glycaemia in vivo in healthy and Type 2 diabetic rats through effects on islet blood perfusion. Telmisartan and ramipril were injected intravenously into anaesthetized non-diabetic Wistar rats or Type 2 diabetic GK (Goto–Kakizaki) rats. In non-diabetic Wistar rats, neither whole PBF (pancreatic blood flow) nor IBF (islet blood flow) were significantly influenced by telmisartan and ramipril, alone or in combination. Renal blood flow was enhanced significantly by telmisartan and ramipril when used in combination, whereas ABF (adrenal blood flow) was not affected by any of the drugs. Telmisartan and ramipril both significantly increased serum insulin levels, but did not influence glycaemia. In Type 2 diabetic GK rats, both whole PBF and IBF were significantly decreased by telmisartan and ramipril, but only when used in combination. Renal blood flow was enhanced significantly by telmisartan and ramipril alone, but not when used in combination, whereas ABF was not affected by any of the drugs. Telmisartan and ramipril both significantly decreased serum insulin levels, and non-additively elevated blood glucose levels. In conclusion, the present study suggests that a local pancreatic RAS (renin–angiotensin system), sensitive to acute administration of telmisartan and ramipril, controls pancreatic IBF and insulin secretion and thereby has an impact on glucose tolerance. Our findings indicate unexpected significant differences in the effects of these agents on islet microcirculation, in vivo insulin secretion and glycaemia between healthy and Type 2 diabetic rats.

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Vitamin D deficiency impairs glucose-stimulated insulin secretion and increases insulin resistance by reducing PPAR-γ expression in nonobese Type 2 diabetic rats

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2015.09.013 ◽

2016 ◽

Vol 27 ◽

pp. 257-265 ◽

Cited By ~ 36

Author(s):

Sunmin Park ◽

Da Sol Kim ◽

Suna Kang

Keyword(s):

Insulin Resistance ◽

Vitamin D ◽

Insulin Secretion ◽

Vitamin D Deficiency ◽

Diabetic Rats ◽

Ppar Γ ◽

Glucose Stimulated Insulin Secretion ◽

Type 2 Diabetic

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Ethanolic Extract ofButea monospermaLeaves Elevate Blood Insulin Level in Type 2 Diabetic Rats, Stimulate Insulin Secretion in Isolated Rat Islets, and Enhance Hepatic Glycogen Formation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/356290 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Mehdi Bin Samad ◽

Ashraf Ul Kabir ◽

Ninadh Malrina D'Costa ◽

Farjana Akhter ◽

Arif Ahmed ◽

...

Keyword(s):

Insulin Secretion ◽

Density Lipoprotein ◽

Diabetic Rats ◽

Hepatic Glycogen ◽

Antihyperglycemic Activity ◽

Isolated Rat Islets ◽

Type 2 Diabetic ◽

Glycogen Formation ◽

Isolated Rat

We measured a vast range of parameters, in an attempt to further elucidate previously claimed antihyperglycemic activity ofButea monosperma. Our study clearly negates the possibility of antidiabetic activity by inhibited gastrointestinal enzyme action or by reduced glucose absorption. Reduction of fasting and postprandial glucose level was reconfirmed (P<0.05). Improved serum lipid profile via reduced low density lipoprotein (LDL), cholesterol, triglycerides (TG), and increased high density lipoprotein (HDL) was also reestablished (P<0.05). Significant insulin secretagogue activity ofB. monospermawas found in serum insulin assay ofB. monospermatreated type 2 diabetic rats (P<0.01). This was further ascertained by our study on insulin secretion on isolated rat islets (P<0.05). Improved sensitivity of glucose was shown by the significant increase in hepatic glycogen deposition (P<0.05). Hence, we concluded that antihyperglycemic activity ofB. monospermawas mediated by enhanced insulin secretion and enhanced glycogen formation in the liver.

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