Phase Of Glucose-stimulated Insulin Release Research Articles

Relative importance of extracellular and intracellular calcium for the two phases of glucose-stimulated insulin release: studies with theophylline.

This study investigated, with perifused rat islets, whether theophylline (2 mM) is able to restore a biphasic release of immunoreactive insulin (IRI) upon glucose stimulation, when calcium entry into β cells is prevented by omission of extracellular Ca (<20 μM) or addition of an antagonist of Ca influx (D 600). Ca omission at the time of glucose stimulation (300 mg/100 ml) reduced IRI release to a small first phase, further diminished by ethyleneglycol-bis-(β-aminoethyl ether) N,N′-tetraacetic acid (EGTA). Ca withdrawal 5 min before glucose increase completely prevented secretion. Theophylline addition augmented the reduced rapid phase of release, but failed to restore it when it was completely suppressed; in contrast, the methylxanthine permitted reappearance of a late phase of IRI release except when EGTA was present. Theophylline introduction during glucose stimulation in the absence of Ca was followed by a rapid, although partial, restoration of IRI release. This effect was inhibited by EGTA and reduc...

Effect of epinephrine and mannoheptulose on early and late phases of glucose-stimulated insulin release

Previous studies have revealed the existence of two separate phases in the glucose-stimulated insulin release. Exposure of microdissected mouse islets to mannoheptulose or epinephrine effectively inhibited both the initial transient release and the second persistent phase of insulin secretion. These results suggest that metabolism of glucose is a prerequisite for both phases of insulin release. The current view of mannoheptulose as an inhibitor of the β-cell phosphorylation of glucose was corroborated by the observation that this drug prevented the increase of fructose-1,6-diphosphate normally observed with increasing glucose levels.

A comparison of the percentages of phosphorus in bituminous and anthracite coals

Neuroendocrine regulatory peptides (NERP-1 and -2) are novel amidated peptides derived from VGF, a polypeptide secreted from neurons and endocrine cells through a regulated pathway. Dr. Nakazato Masamitsu reported that NERP-1 and -2 may have a local modulator function on the human endocrine system, and clearly showed expression of NERP-1 and -2 in human pancreas islets. Based on these data, we investigated the alteration of insulin secretion, insulin granule-related protein, and pancreas-specific transcription factors in response to NERPs expression. We confirmed the expression of NERP-1 and -2 in the pancreas of a human diabetes patient, in addition to diabetic animal models. When INS1 cells and primary rat islets were incubated with 10 nM NERPs for 3 days, glucose-stimulated insulin secretion levels were blunted by NERP-1 and -2. The number of insulin granules released from the readily releasable pool, which is associated with the first phase of glucose-stimulated insulin release, was decreased by NERP-1 and -2. Insulin granule-related proteins and mRNAs were down-regulated by NERP-2 treatment. NERP-2 decreased the expression of BETA2/NeuroD and insulin and controlled the nucleo-cytoplasmic translocation of FOXO1 and Pdx-1. We observed that NERP-2 levels were dramatically increased in diabetic pancreas. In conclusion, NERP-2 may play an important role in insulin secretion through the regulation of insulin secretory granules and β-cell transcription factors. In addition, NERP-2 expression is increased in diabetic conditions. Therefore, we suggest that NERPs may be potent endogenous suppressors of glucose-dependent insulin secretion.