Nitric oxide-related pancreatic endocrine responses to hyperglycaemia in the conscious calf

Edwards, A V; Ghatei, M.A.; Bloom, Stephen R.

doi:10.1007/bf01919371

Cited by 4 publications

(2 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Laychock et al [7] incubated isolated rat islets for 20 min with l-NMMA and demonstrated that glucose-and l-arginine-stimulated insulin release depends partly on the endogenous formation of NO and cGMP. Furthermore, continuous infusion of glucose together with a NOS inhibitor into conscious calves resulted in reduced plasma insulin and elevated plasma glucose concentration [22].…”

Section: Discussionmentioning

confidence: 99%

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

Spinas¹,

Laffranchi²,

Francoys³

et al. 1998

Diabetologia

View full text Add to dashboard Cite

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]

show abstract

Section: Discussionmentioning

confidence: 99%

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

Spinas¹,

Laffranchi²,

Francoys³

et al. 1998

Diabetologia

View full text Add to dashboard Cite

show abstract

“…It has also been suggested that the inhibition of glucose-induced insulin secretion is due to suppression of phosphofructokinase activity in glycolysis (Tsuura et al 1998) or S-nitrosylation of thiol residues in proteins which mediate stimulus-secretion coupling (Panagiotidis et al 1995;Sj oholm, 1996). Others have reported that it stimulates the release of insulin both in vitro (Spinas et al 1998) and in vivo in various species, including the human (Edwards et al 1994;Bilski et al 1995;Konturek et al 1997), possibly acting by inducing calcium release from mitochondria (Laffranchi et al 1995).…”

mentioning

confidence: 99%

The Role of Nitric Oxide in Mediating Pancreatic Endocrine Responses to Insulin‐Induced Hypoglycaemia in the Conscious Calf

Edwards

Ghatei

Bloom

et al. 1999

Experimental Physiology

Self Cite

View full text Add to dashboard Cite

The role of nitric oxide (NO) in mediating pancreatic endocrine responses to moderate hypoglycaemia has been investigated in conscious unrestrained calves. The synthesis of endogenous NO was inhibited by the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mg kg-1 I.A.), while sodium nitroprusside was infused continuously (2-4 microg min-1 kg-1 I.V.) to mimic the tonic production of NO. This effectively abolished the rise in plasma pancreatic polypeptide (PP) concentration during moderate hypoglycaemia (0.7 nmol kg-1 insulin I.V.) and significantly reduced the response to more intense hypoglycaemia (2.0 nmol kg-1 insulin I. V.). In contrast, the glucagon response was not significantly affected in either group, although consistently higher plasma glucagon values were obtained in response to the higher dose of insulin following the administration of L-NAME. It is concluded that, in the absence of L-NAME, production of NO contributes to the PP response, but not the glucagon response to hypoglycaemia in this species under physiological conditions.

show abstract