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]
The results indicate a role for C-type natriuretic polypeptide and its receptor in the induction of penile erection and its possible future therapeutic use for erectile dysfunction.
The occurrence and coexistence of peptides of the insulin-like growth factor (IGF)/insulin superfamily were investigated in the ovary and gastro-intestinal tract of the protochordate Ciona intestinalis. Antisera specific for mammalian IGF-I, insulin and relaxin were used in a double-immunofluorescence method on paraffin sections and with an immunogold technique on consecutive semi-thin sections. IGF-I and relaxin immunoreactions but no insulin immunoreactions occurred in the ovary and were confined to medium-sized and mature follicle cells. Two subpopulations of reacting follicular cells were present: those containing only IGF-I immunoreactivity (5%) and those containing IGF-I and relaxin immunoreactivities (95%). In the gastro-intestinal tract, IGF-I and insulin immunoreactions coexisted, whereas no relaxin immunoreactions were obtained. Gel chromatography and radioimmunoassay in Ciona ovary revealed IGF-I immunoreactivity in two peaks with apparent molecular masses of approximately 16 kDa and 3 kDa. The present results indicate that (1) the same IGF-I-related peptide probably occurs in gastro-intestinal tract and ovary, (2) three different members of the insulin/IGF family of peptides are probably present in protochordates, (3) different types of coexistence of these peptides seem to exist in protochordates, i.e. an IGF-I-related peptide and an insulin-related peptide in the digestive tract and, as shown previously, in central nervous system, and the IGF-I-related peptide and relaxin in the ovary, (4) an IGF-I-related peptide and relaxin may be involved in oocyte maturation in the protochordate ovary.
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