Pancreatic effects insulin release stimulation

Diagrammatic representation of insulin secretion from pancreatic fi cells. The sequence of events of insulin secretion coupled to glucose entry into fi cells consists of glucokinase action, ATP production, inhibition of the ATP-sensitive K+ channel, membrane depolarization, Ca + influx, and insulin release. Neurotransmitters acetylcholine and norepinephrine stimulate and inhibit insulin secretion via trimeric G-proteins Gq and Gj, respectively. Glucagon-like peptide (GLP) promotes insulin release via the G-protein G. Sulfonamides and diazoxide have direct effects on sulfonylurea receptors (SURs) the former promotes insulin release and the latter inhibits insulin release. +, Stimulation —, inhibition. Other abbreviations are given in the text. 

As to be expected from a peptide that has been highly conserved during evolution, NPY has many effects, e.g. in the central and peripheral nervous system, in the cardiovascular, metabolic and reproductive system. Central effects include a potent stimulation of food intake and appetite control [2], anxiolytic effects, anti-seizure activity and various forms of neuroendocrine modulation. In the central and peripheral nervous system NPY receptors (mostly Y2 subtype) mediate prejunctional inhibition of neurotransmitter release. In the periphery NPY is a potent direct vasoconstrictor, and it potentiates vasoconstriction by other agents (mostly via Yi receptors) despite reductions of renal blood flow, NPY enhances diuresis and natriuresis. NPY can inhibit pancreatic insulin release and inhibit lipolysis in adipocytes. It also can regulate gut motility and gastrointestinal and renal epithelial secretion. 

Limited data are available on in vitro effects of barium on the endocrine system. Studies done with isolated pancreatic islet cells from mice show barium is transported across the cell membrane and incorporated into organelles, especially the mitochondria and secretory granules (Berggren et al. 1983). Barium was found to increase cytoplasmic calcium consequently, the insulin- releasing action of barium may be mediated by calcium. Barium has also been found capable of stimulating the calcitonin secretion system of the thyroid in pigs (Pento 1979). 

Roza and Berman 1971 Schott and McArdle 1974) and is used as an antidote in cases of acute barium poisoning. Calcium and magnesium suppress uptake of barium in vitro in pancreatic islets. Conversely, barium, in low concentrations, stimulate calcium uptake in these cells. Although the data are insufficient to determine the significance of these findings to human health effects, displacement of calcium may be the mechanism by which barium stimulates insulin release (Berggren et al. 1983). 

Fig. 18. Effect of glucose on insulin release, glucose oxidation, pentose phosphate shunt, NADH/NAD +, NADPH/NADP"1", GSH/GSSG ratios and Ca + uptake of rat pancreatic islets. In a concentration range up to 16.7 mM, glucose-mediated stimulation of insulin secretion is closely parallelled by increases in glucose oxidation, pentose phosphate shunt activity, the NADH/NAD+, NADPH/NADP+, GSH/GSSG ratios and Ca2+ uptake (Ammon and Wahl, 1994).

VIP is released from pancreatic neurons by vagus stimulation (Holst et al., 1984). It increases insulin secretion in a glucose-dependent manner (Jensen etal., 1978 Ahren etal., 1986 Holst etal., 1987 Wahl etal., 1993). Although released by vagus stimulation, its action is not related to a cholinergic effect. Previously, Wahl et al. (1993) reported that VIP increased glucose-mediated Ca2+ uptake into pancreatic islets which paralleled insulin secretion. This effect was not caused by interference with K+ efflux. 

Enkephalins and endorphins have been found to stimulate insulin release (Ipp etal., 1978 Hermansen, 1983. Verspohl etal., 1986a). In this connection it was also demonstrated that opioid -receptors do not play a role in pancreatic islets but that the insulinotropic effect of low concentrations of Met-enkephalin is mediated via S-receptors (Verspohl et al., 1986a). 

Like sulfonylureas, repaglinide stimulates insulin release by closing ATP-dependent channels in pancreatic fi cells. The drug is absorbed rapidly from the GI tract, and peak blood levels are obtained within 1 hour with a of 1 hour. These features permit multiple preprandial use as compared with the classical once- or twice-daily dosing of sulfonylureas. Repaglinide is metabolized primarily by the liver to inactive derivatives and should be used cautiously in patients with hepatic insufficiency. Caution is also indicated in patients with renal insufficiency. The major adverse effect of repaghnide is hypoglycemia. 

Finally, glucagon stimulates insulin release from the (3 cells of the pancreas. Whether this is a paracrine effect or an endocrine effect has not been established. The pattern of blood flow in the pancreatic islet cells is believed to bathe the (3 cells... 

Fig. 43.6. Effects of epinephrine on fuel metabolism and pancreatic endocrine function. Epinephrine (Epi) stimulates glycogen breakdown in muscle and liver, gluconeogenesis in liver, and lipolysis in adipose tissue. Epinephrine further reinforces these effects because it increases the secretion of glucagon, a hormone that shares many of the same effects as epinephrine. Epi also inhibits insulin release but stimulates glucagon release from the pancreas.

Diazoxide increases blood glucose concentration (diazoxide-induced hyperglycemia) by several different mechanisms by inhibiting pancreatic insulin secretion, by stimulating release of catecholamines, or by increasing hepatic release of glucose (6,9). The precise mechanism of inhibition of insulin release has not been elucidated but, possibly, may result from an effect of diazoxide on cell-membrane potassium channels and calcium flux. 

Flavones and flavonols, especially quercetin, have been reported to possess antidiabetic activity. A cohort study that predicted the effects of flavonoids on chronic diseases showed that a trend toward a reduction in risk of type 2 diabetes was associated with higher quercetin and myricetin intakes. Vessal et al. reported that quercetin brings about the regeneration of pancreatic islets and increases insulin release in streptozotocin-induced diabetic rats [133]. Also in another study, Hif and Howell reported that quercetin stimulates insulin release and enhances Ca " uptake from isolated islet cells which suggest a place for flavonoids in non-insulin-dependent diabetes [134, 135]. 

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