Acute regulation of pancreatic islet microcirculation and glycaemia by telmisartan and ramipril: discordant effects between normal and Type 2 diabetic rats

Abstract

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.

Telmisartan Potentiates Insulin Secretion via Ion Channels, Independent of the AT1 Receptor and PPARγ

“…We speculated that the glucose-lowering effect of telmisartan was delayed and weakened in 11-wk-old mice, possibly owing to the progression of insulin resistance and the deterioration of β-cell function in db/db mice. In addition, our data in vivo were not completely consistent with the previous results of telmisartan in regard to acute regulation of pancreatic islet microcirculation and glycaemia ( Olverling et al, 2013 ). The reasons for this discrepancy might conceivably relate to differences in concentrations of drug administration in experiments, and different impaired β-cell function state caused by species and age of the animal model.…”

Functional status of microvascular vasomotion is impaired in spontaneously hypertensive rat

“…In a study reported by Anna Olverling et al . 17 , local pancreatic renin-angiotensin system (RAS) controls pancreatic islet blood flow and insulin secretion and thereby may affect blood glucose level. Furthermore, several pancreatic islet RAS signaling pathways seem to be up-regulated by hypertension 18 , 19 .…”