Electrolyte Changes and Metabolic Effects of Lisinopril/Bendrofluazide Treatment Results From a Randomized, Double-Blind Study With Parallel Groups

Haenni, Arvo; Andersson, Per-Erik; Lind, Lars; Berne, Christian; Lithell, Hans

doi:10.1093/ajh/7.7.615

Cited by 34 publications

(19 citation statements)

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“…However, these drugs have been shown in some studies to improve the secretion and action of insulin. Although the effects of ACE-inhibition on insulin sensitivity are not clear, the beneficial effects of ACE-inhibition for insulin release have been shown in many hypertensive patients [40,41,42]. Moreover, intravenous infusion of Ang II has suppressed both basal and especially glucose-stimulated insulin secretion in humans [43].…”

Section: Discussionmentioning

confidence: 99%

Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

2004

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Aims/hypothesis. A local angiotensin-generating system has been found in the exocrine pancreas. This study aimed, primarily, to investigate the existence of a local angiotensin-generating system in the pancreatic islets and, secondly, to elucidate its role in regulating insulin secretion. Methods. Real-time RT-PCR and western blot were used to investigate if angiotensin-generating components are present in the mouse pancreatic islets, which are subject to regulation by islet transplantation. The localisation of AT 1 -receptors in islets was investigated by immunohistochemistry. Batch-type incubations of isolated islets were applied for studying the influence of angiotensin II on the glucose-stimulated insulin release, glucose oxidation and (pro)insulin, and total protein biosynthesis. Results. Major components, namely angiotensinogen, ACE, AT 1 -and AT 2 -receptors, were expressed in endogenous islets. AT 1 -receptors were localised to pancreatic beta cells. Exposure of the isolated islets to angiotensin II induced a dose-dependent inhibition of glucose-stimulated insulin release and inhibited (pro)insulin biosynthesis. This inhibitory action was fully preventable by pretreatment of the islets with losartan, an AT 1 -receptor antagonist. We also investigated if the expression of these components was changed after islet transplantation. Notably, a markedly increased expression of mRNA for the AT 1 -receptor was observed in islets retrieved from 4-week-old syngeneic islet transplants, a finding that was confirmed at the protein level. Conclusion/interpretation. These data indicate the existence of an islet angiotensin-generating system of potential importance in the physiological regulation of glucose-induced insulin secretion, thus diabetes mellitus. The increased expression of the AT 1 -receptor in islet transplants could have relevance to islet-graft function. [Diabetologia (2004) 47:240-248]

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Section: Discussionmentioning

confidence: 99%

Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

2004

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“…Moreover, there is some evidence that ACE inhibition or Ang II receptor blockade protects from the development of glucose intolerance in hypertensive patients [14][15][16], and experimental manipulation of systemic RAS in humans can influence insulin secretory responses [14][15][16][17]. However, it is difficult for in vivo studies or experiments using the whole pancreas to differentiate between effects on the pancreatic vasculature and direct effects on islet endocrine function, and the inhibitory effects of Ang II on insulin release in vivo or in the perfused pancreas have been attributed to its vasoconstrictive effects on islet blood flow [18,19].…”

Section: Introductionmentioning

confidence: 99%

Direct regulation of insulin secretion by angiotensin II in human islets of Langerhans

Ramracheya

Müller

et al. 2006

Diabetologia

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Aims/hypothesis: This study aimed to identify the expression of angiotensin II receptors in isolated human islets and beta cells and to examine the functional consequences of their activation. Materials and methods: Singlecell RT-PCR was used to identify whether human islet cells express mRNA for type 1 angiotensin II receptors (AT 1 ), and western blotting was used to determine AT 1 protein expression by human islets and MIN6 beta cells. We measured changes in intracellular calcium by microfluorimetry using Fura 2-loaded MIN6 cells and human islet cells. Dynamic insulin secretory responses were determined by RIA following perifusion of human islets and MIN6 cells. Results: Human islets expressed mRNAs for both the angiotensin precursor, angiotensinogen, and for angiotensin-converting enzyme. In addition, human and mouse beta cells expressed AT 1 . These were functionally coupled to increases in intracellular calcium, which occurred at least in part through phospholipase-C-sensitive mechanisms and calcium influx through voltage-operated calcium channels.Short-term exposure of human islets and MIN6 cells to angiotensin II caused a rapid, short-lived initiation of insulin secretion at 2 mmol/l glucose and potentiation of insulin secretion induced by glucose (at 8 and 16.7 mmol/l). Conclusions/interpretation: These data demonstrate that the AT 1 is expressed by beta cells and that angiotensin II effects a short-lived and direct stimulation of human and mouse beta cells to promote insulin secretion, most probably through elevations in intracellular calcium. Locally produced angiotensin II may be important in regulating a coordinated insulin secretory response from beta cells.

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“…Iwase et al (7) demonstrated that orally administered insulin secretagogues acutely increased the islet blood flow. Moreover, renin-angiotensin system (RAS) inhibitors that regulate the islet blood flow, such as ACE inhibitors and angiotensin II receptor blockers (ARBs), increased insulin secretion in response to glucose administration (8)(9)(10). In addition to RAS inhibitors, some vasoactive drugs enhance pancreatic islet blood flow, augment insulin secretion, and improve glucose tolerance (11,12).…”

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confidence: 99%

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

et al. 2014

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Endothelial cells are considered to be essential for normal pancreatic β-cell function. The current study attempted to demonstrate the role of insulin receptor substrate-2 (Irs2) in endothelial cells with regard to insulin secretion. Endothelial cell–specific Irs2 knockout (ETIrs2KO) mice exhibited impaired glucose-induced, arginine-induced, and glucagon-induced insulin secretion and showed glucose intolerance. In batch incubation and perifusion experiments using isolated islets, glucose-induced insulin secretion was not significantly different between the control and the ETIrs2KO mice. In contrast, in perfusion experiments, glucose-induced insulin secretion was significantly impaired in the ETIrs2KO mice. The islet blood flow was significantly impaired in the ETIrs2KO mice. After the treatment of these knockout mice with enalapril maleate, which improved the islet blood flow, glucose-stimulated insulin secretion was almost completely restored to levels equal to those in the control mice. These data suggest that Irs2 deletion in endothelial cells leads to a decreased islet blood flow, which may cause impaired glucose-induced insulin secretion. Thus, Irs2 in endothelial cells may serve as a novel therapeutic target for preventing and ameliorating type 2 diabetes and metabolic syndrome.

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Electrolyte Changes and Metabolic Effects of Lisinopril/Bendrofluazide Treatment Results From a Randomized, Double-Blind Study With Parallel Groups

Cited by 34 publications

References 0 publications

Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

Direct regulation of insulin secretion by angiotensin II in human islets of Langerhans

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

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