Glucose-induced islet hyperemia is mediated by nitric oxide

Moldovan, Stefan; Livingston, Edward H.; Zhang, Ren Shang; Kleinman, Robert; Girth, Paul; Brunicardi, F. Charles

doi:10.1016/s0002-9610(99)80066-x

Cited by 52 publications

(51 citation statements)

References 14 publications

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“…It has previously been demonstrated that hyperglycemia may increase the blood perfusion of the islets (34), presumably mediated by nitric oxide (35). Diazoxide increased the values to ϳ9 mmol/l, whereas NNC 55-0118 had no such effects.…”

Section: Discussionmentioning

confidence: 88%

KATP Channels and Pancreatic Islet Blood Flow in Anesthetized Rats

et al. 2003

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K ATP channels are important for insulin secretion and depolarization of vascular smooth muscle. In view of the importance of drugs affecting K ATP channels in the treatment of diabetes, we investigated the effects of these channels on splanchnic blood perfusion in general and pancreatic islet blood flow in particular. We treated anesthetized Sprague-Dawley rats with the K ATP channel openers diazoxide or NNC 55-0118 or the K ATP channel closer glipizide. Both diazoxide and NNC 55-0118 dose-dependently increased total pancreatic and islet blood flow in the presence of moderate hyperglycemia, but had no effects on the blood perfusion of other splanchnic organs. Diazoxide markedly lowered the mean arterial blood pressure and thus increased vascular conductance in all organs studied. NNC 55-0118 had much smaller effects on the blood pressure. Glipizide did not affect total pancreatic blood flow, but decreased islet blood flow by 50% in the presence of hypoglycemia. We conclude that K ATP channels actively participate in the blood flow regulation of the pancreatic islets and that substances affecting such channels may also influence islet blood flow.

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Section: Discussionmentioning

confidence: 88%

KATP Channels and Pancreatic Islet Blood Flow in Anesthetized Rats

et al. 2003

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“…These experiments are, however, difficult to compare with our perifusion system since in vivo administration or pancreas perfusion with NOS inhibitors may exert additional systemic effects such as vasoconstriction [23] or interfere with neuronal mechanisms which could affect insulin release [26]. Furthermore, NOS inhibition may also cause an increase in islet capillary blood flow [27].…”

Section: Discussionmentioning

confidence: 99%

The early phase of glucose-stimulated insulin secretion requires nitric oxide

Spinas¹,

Laffranchi²,

Francoys³

et al. 1998

Diabetologia

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Nitric oxide (nitrogen monoxide; NO) is an important messenger molecule in various cell types, e. g. endothelial cells [1], neurons [2], or T lymphocytes [3]. However, when produced in large amounts and over prolonged periods of time, e. g. by macrophages [4], NO is cytotoxic.In pancreatic beta cells NO produced upon activation of the inducible isoform of NO synthase by cytokines causes beta-cell destruction [5]. There is also evidence that NO could function as signal transmitter in beta cells. However, results obtained in pursuit of a possible involvement of NO in the signalling pathway of insulin secretion are controversial. Some investigations provided evidence that NO, presumably produced by a calcium/calmodulin-dependent constitutive NO synthase (NOS), participates in the signal transduction pathway mediating insulin secretion [6], and that L-arginine-derived NO mediates insulin secretion via stimulation of guanylate cyclase and cGMP formation [7]. Others found no evidence for endogenously produced NO being involved in the initiation of secretagogue-induced insulin release [8] or reported that L-arginine-derived NO may even inhibit insulin release [9].Recently, Willmott et al. [10] showed that beta cells preloaded with tryptamine, which accumulates in insulin-containing granules and is co-secreted with insulin, respond to NO by mobilizing Ca 2+ from the endoplasmic reticulum accompanied by a release of tryptamine from the cells. These data corroborate our previous finding that exogenously added NO Diabetologia (1998) Summary Nitric oxide (nitrogen monoxide, NO) acts as a signal transducer in a variety of cells. In the present study rat pancreatic islets were perifused with physiologically relevant glucose concentrations in the presence or absence of various NO-modulating agents. Perifusion in the presence of 0.1±1 mmol/l of the NO synthase inhibitor, N G -monomethyl-L-arginine or of 10 mmol/l of the NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), resulted in an inhibition of the early phase of glucose-stimulated insulin secretion by 60±65 % and 46 %, respectively. Light-and electron-microscopic studies revealed that pancreatic islets constitutively express NO-synthase in alpha and delta cells, where it is confined to the secretory granules. Therefore, these data indicate that NO may be important in the signal transduction pathway of the early phase of glucose-stimulated insulin secretion.[ Diabetologia (1998) 41: 292±299]

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“…1). This gas has previously been described as essential for the high normal islet blood flow and as a mediator of further increasing of islet blood flow during hyperglycemia following vagal stimulation (13,14). An interesting part of the present study by Hashimoto et al (10) is that ACE inhibition was used to improve islet blood flow in the endothelial cell-specific Irs2 knockout mice and to reverse their defect insulin secretion.…”

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confidence: 63%