scholarly journals Cytosolic ratios of free [NADPH]/[NADP+] and [NADH]/[NAD+] in mouse pancreatic islets, and nutrient-induced insulin secretion

1987 ◽  
Vol 241 (1) ◽  
pp. 161-167 ◽  
Author(s):  
C J Hedeskov ◽  
K Capito ◽  
P Thams
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Coupling Factor ◽  
Mouse Pancreatic Islets ◽  
Cell Depolarization ◽  
K Permeability ◽  
Cell Glucose ◽  
Stimulation Of

When the extracellular concentration of glucose was raised from 3 mM to 7 mM (the concentration interval in which beta-cell depolarization and the major decrease in K+ permeability occur), the cytosolic free [NADPH]/[NADP+] ratio in mouse pancreatic islets increased by 29.5%. When glucose was increased to 20 mM, a 117% increase was observed. Glucose had no effect on the cytosolic free [NADH]/[NAD+] ratio. Neither the cytosolic free [NADPH]/[NADP+] ratio nor the corresponding [NADH]/[NAD+] ratio was affected when the islets were incubated with 20 mM-fructose or with 3 mM-glucose + 20 mM-fructose, although the last-mentioned condition stimulated insulin release. The insulin secretagogue leucine (10 mM) stimulated insulin secretion, but lowered the cytosolic free [NADPH]/[NADP+] ratio; 10 mM-leucine + 10 mM-glutamine stimulated insulin release and significantly enhanced both the [NADPH]/[NADP+] ratio and the [NADH]/[NAD+] ratio. It is concluded that the cytosolic free [NADPH]/[NADP+] ratio may be involved in coupling beta-cell glucose metabolism to beta-cell depolarization and ensuing insulin secretion, but it may not be the sole or major coupling factor in nutrient-induced stimulation of insulin secretion.

scholarly journals Effect of perchlorate on calcium uptake and insulin secretion in mouse pancreatic islets

1987 ◽  
Vol 248 (1) ◽  
pp. 109-115 ◽  
Author(s):  
J Sehlin
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Oxidation ◽  
Calcium Uptake ◽  
Maximum Effect ◽  
Mouse Pancreatic Islets ◽  
Stimulus Secretion Coupling ◽  
Ca2 Channels

Microdissected beta-cell-rich pancreatic islets of non-inbred ob/ob mice were used in studies of how perchlorate (CIO4-) affects stimulus-secretion coupling in beta-cells. CIO4- at 16 mM potentiated D-glucose-induced insulin release, without inducing secretion at non-stimulatory glucose concentrations. The potentiation mainly applied to the first phase of stimulated insulin release. In the presence of 20 mM-glucose, the half-maximum effect of CIO4- was reached at 5.5 mM and maximum effect at 12 mM of the anion. The potentiation was reversible and inhibitable by D-mannoheptulose (20 mM) or Ca2+ deficiency. CIO4- at 1-8 mM did not affect glucose oxidation. The effects on secretion were paralleled by a potentiation of glucose-induced 45Ca2+ influx during 3 min. K+-induced insulin secretion and 45Ca2+ uptake were potentiated by 8-16 mM-CIO4-. The spontaneous inactivation of K+-induced (20.9 mM-K+) insulin release was delayed by 8 mM-CIO4-. The anion potentiated the 45Ca2+ uptake induced by glibenclamide, which is known to depolarize the beta-cell. Insulin release was not affected by 1-10 mM-trichloroacetate. It is suggested that CIO4- stimulates the beta-cell by affecting the gating of voltage-controlled Ca2+ channels.

Direct effect of parathyroid hormone on insulin secretion from pancreatic islets

1990 ◽  
Vol 258 (6) ◽  
pp. E975-E984 ◽  
Author(s):  
G. Z. Fadda ◽  
M. Akmal ◽  
L. G. Lipson ◽  
S. G. Massry
Keyword(s):  
Insulin Secretion ◽  
Parathyroid Hormone ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Direct Effect ◽  
Indirect Evidence ◽  
Cytosolic Calcium ◽  
Dependent Manner ◽  
Stimulation Of

Indirect evidence indicates that parathyroid hormone (PTH) interacts with pancreatic islets and modulates their insulin secretion. This property of PTH has been implicated in the genesis of impaired insulin release in chronic renal failure. We examined the direct effect of PTH-(1-84) and PTH-(1-34) on insulin release using in vitro static incubation and dynamic perifusion of pancreatic islets from normal rats. Both moieties of the hormone stimulated in a dose-dependent manner glucose-induced insulin release but higher doses inhibited glucose-induced insulin release. This action of PTH was modulated by the calcium concentration in the media. The stimulatory effect of PTH was abolished by its inactivation and blocked by its antagonist [Tyr-34]bPTH-(7-34)NH2. PTH also augmented phorbol ester (TPA)-induced insulin release, stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation by pancreatic islets, and significantly increased (+50 +/- 2.7%, P less than 0.01) their cytosolic calcium. Verapamil inhibited the stimulatory effect of PTH on insulin release. The data show that 1) pancreatic islets are a PTH target and may have PTH receptors, 2) stimulation of glucose-induced insulin release by PTH is mediated by a rise in cytosolic calcium, 3) stimulation of cAMP production by PTH and a potential indirect activation of protein kinase C by PTH may also contribute to the stimulatory effect on glucose-induced insulin release, and 4) this action of PTH requires calcium in incubation or perifusion media.

Nitric oxide donor SIN-1 inhibits insulin release

1996 ◽  
Vol 271 (4) ◽  
pp. C1098-C1102 ◽  
Author(s):  
A. Sjoholm
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Kinase C ◽  
Stimulus Secretion Coupling

Preceding the onset of insulin-dependent diabetes mellitus, pancreatic islets are infiltrated by macrophages secreting interleukin-1 beta, which exerts cytotoxic and inhibitory actions on islet beta-cell insulin secretion through induction of nitric oxide (NO) synthesis. The influence of the NO donor 3-morpholinosydnonimine (SIN-1) on insulin secretion from isolated pancreatic islets in response to various secretagogues was investigated. Stimulation of insulin release evoked by glucose, phospholipase C activation with carbachol, and protein kinase C activation with phorbol ester were obtained by SIN-1, whereas the response to adenylyl cyclase activation or K(+)-induced depolarization was not affected. It is concluded that enzymes involved in glucose catabolism, phospholipase C or protein kinase C, may be targeted by NO. Reversal of SIN-1 inhibition of glucose-stimulated insulin release by dithiothreitol suggests that NO may inhibit insulin secretion partly by S-nitrosylation of thiol residues in key proteins in the stimulus-secretion coupling. These adverse effects of NO on the beta-cell stimulus-secretion coupling may be of importance for the development of the impaired insulin secretion characterizing diabetes mellitus.

scholarly journals Opposite effects of starvation on oxidation of [14C]adenosine and adenosine-induced insulin release by isolated mouse pancreatic islets

1978 ◽  
Vol 176 (2) ◽  
pp. 619-621 ◽  
Author(s):  
A Andersson
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Metabolic Flux ◽  
Insulin Biosynthesis ◽  
Insulin Production ◽  
Stimulate Insulin Secretion ◽  
Mouse Pancreatic Islets

To test further the hypothesis that ribonucleosides stimulate insulin secretion and biosynthesis by producing metabolic signals, the effects of starvation on adenosine-stimulated insulin production and the oxidation of adenosine by isolated mouse pancreatic islets were examined. No direct correlation was found between the metabolic flux and insulin secretion, since the starvation-induced impairment of the adenosine-stimulated insulin secretion was accompanied by an increased rate of adenosine oxidation. Adenosine-stimulated insulin biosynthesis was, however, unaffected by starvation.

Diazoxide unmasks glucose inhibition of insulin release by counteracting entry of Ca2+

1988 ◽  
Vol 255 (4) ◽  
pp. E422-E427 ◽  
Author(s):  
P. Bergsten ◽  
E. Gylfe ◽  
N. Wesslen ◽  
B. Hellman
Keyword(s):  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Secretory Response ◽  
Glucose Stimulation ◽  
Glucose Inhibition ◽  
Insulin Secretory Response ◽  
Stimulation Of

The interaction of diazoxide with the effects of glucose on the insulin-releasing mechanism was analyzed in beta-cell-rich pancreatic islets isolated from ob/ob mice. When added at a concentration of 400 microM to a medium containing 1.28 mM Ca2+, diazoxide converted glucose stimulation of insulin release into inhibition. Further addition of 2 mM theophylline restored the insulin secretory response to glucose. The paradoxical glucose inhibition of insulin release was accounted for by a diazoxide interaction with the entry of Ca2+, unmasking a capacity of the sugar to lower cytoplasmic Ca2+ below its resting concentration.

scholarly journals GPRC6A Mediates the Effects of l-Arginine on Insulin Secretion in Mouse Pancreatic Islets

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4608-4615 ◽  
Author(s):  
Min Pi ◽  
Yunpeng Wu ◽  
Nataliya I Lenchik ◽  
Ivan Gerling ◽  
L. Darryl Quarles
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Ex Vivo ◽  
Β Cells ◽  
Direct Role ◽  
Mouse Pancreatic Islets ◽  
Islet Size ◽  
G Protein Coupled ◽  
Stimulation Of

Abstract l-Arginine (l-Arg) is an insulin secretagogue, but the molecular mechanism whereby it stimulates insulin secretion from β-cells is not known. The possibility that l-Arg regulates insulin secretion through a G protein-coupled receptor (GPCR)-mediated mechanism is suggested by the high expression of the nutrient receptor GPCR family C group 6 member A (GPRC6A) in the pancreas and TC-6 β-cells and the finding that Gprc6a−/]minus] mice have abnormalities in glucose homeostasis. To test the direct role of GPRC6A in regulating insulin secretion, we evaluated the response of pancreatic islets derived from Gprc6a−/]minus] mice to l-Arg. We found that the islet size and insulin content were decreased in pancreatic islets from Gprac6a−/]minus] mice. These alterations were selective for β-cells, because there were no abnormalities in serum glucagon levels or glucagon content of islets derived from Gprac6a−/]minus] mice. Significant reduction was observed in both the pancreatic ERK response to l-Arg administration to Gprc6a−/]minus] mice in vivo and l-Arg-induced insulin secretion and production ex vivo in islets isolated from Gprc6a−/]minus] mice. l-Arg stimulation of cAMP accumulation in isolated islets isolated from Gprc6a−/]minus] mice was also diminished. These findings suggest that l-Arg stimulation of insulin secretion in β-cells is mediated, at least in part, through GPRC6A activation of cAMP pathways.

Influence of thiol groups, calcium, and glucose metabolism on cholinergic-induced insulin release and on methylscopolamine binding to muscarinic receptors in pancreatic islets of the rat

1985 ◽  
Vol 109 (3) ◽  
pp. 355-360 ◽  
Author(s):  
V. Grill ◽  
K. Fåk
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Muscarinic Receptors ◽  
Priming Effect ◽  
Thiol Groups ◽  
Short Term ◽  
Effect Of Glucose ◽  
Stimulation Of

Abstract. Short-term regulation of [3H]methylscopolamine binding to muscarinic receptors and acetylcholineinduced stimulation of insulin release was investigated in pancreatic islets of the rat. Binding of methylscopolamine was reversible; 47% of label was displaced 10 min and 70% 30 min after addition of unlabelled substance. 0.1 mm chloromercuribensoic acid, when present during binding incubations, inhibited binding by 54%, whereas acetylcholine-induced insulin release was unaffected by the presence of the thiol reactant. Pre-incubation for 60 min in a calcium-deprived medium or in the presence of 50 μm trifluoroperazine likewise inhibited binding. Pre-incubation with 1.0 mm 3-isobutyl-l-methylxanthine or 16.7 m glucose failed to influence subsequent binding although acetylcholine-induced insulin release was 4-fold enhanced by priming with glucose. We conclude that 1) binding to muscarinic receptors is influenced by thiol interaction, 2) short-term alterations in calcium fluxes influence binding, whereas short-term changes in cyclic AMP (cAMP) or glucose metabolism do not, 3) a priming effect of glucose on insulin secretion is not mediated by changes in receptor binding.

Slow and fast oscillations of cytoplasmic Ca2+ in pancreatic islets correspond to pulsatile insulin release

1995 ◽  
Vol 268 (2) ◽  
pp. E282-E287 ◽  
Author(s):  
P. Bergsten
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Secretory Response ◽  
Similar Frequency ◽  
Mouse Pancreatic Islets ◽  
Pulsatile Insulin Secretion ◽  
Fast Oscillations ◽  
Sustained Increase

Cytoplasmic Ca2+ concentration ([Ca2+]i) and insulin secretion were monitored in single ob/ob mouse pancreatic islets stimulated by glucose. After culture in 5.5 mM of the sugar, islets responded to 11 mM glucose with pulsatile insulin secretion synchronized with oscillations of [Ca2+]i (0.3-0.5/min). Most islets also showed superimposed regular rapid [Ca2+]i oscillations and insulin transients of similar frequency. Whereas the amplitude of the slow insulin pulses increased in 20 mM glucose, the [Ca2+]i oscillations were replaced by a sustained increase. After culture in the absence of sugar, there was little rise of [Ca2+]i during exposure to 11 mM glucose and only a slight secretory response, which, however, was pulsatile. The slow secretory pulses in the presence of 11 mM glucose were augmented after culture in 11 or 20 mM glucose despite a sustained elevation of [Ca2+]i. Although pulsatile insulin release was not always associated with [Ca2+]i oscillations, the data indicate that the slow and fast [Ca2+]i oscillations do correspond to pulsatile insulin secretion.

scholarly journals An inhibitory role for polyamines in protein kinase C activation and insulin secretion in mouse pancreatic islets

1986 ◽  
Vol 237 (1) ◽  
pp. 131-138 ◽  
Author(s):  
P Thams ◽  
K Capito ◽  
C J Hedeskov
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Pancreatic Islets ◽  
Kinase C ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets ◽  
Protein Kinase C Activation ◽  
Stimulation Of

The occurrence and function of polyamines in protein kinase C activation and insulin secretion in mouse pancreatic islets were studied. Determination of polyamines in mouse islets revealed 0.9 +/- 0.3 (mean +/- S.E.M., n = 6) pmol of putrescine, 11.7 +/- 3.2 (8) pmol of spermidine and 3.7 +/- 0.6 (8) pmol of spermine per islet, corresponding to intracellular concentrations of 0.3-0.5 mM-putrescine, 3.9-5.9 mM-spermidine and 1.2-1.9 mM-spermine in mouse islets. Stimulation of insulin secretion by glucose, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) or the sulphonylurea glibenclamide did not affect these polyamine contents. In accordance with a role for protein kinase C in insulin secretion, TPA stimulated both protein kinase C activity and insulin secretion. Stimulation of insulin secretion by TPA was dependent on a non-stimulatory concentration of glucose and was further potentiated by stimulatory concentrations of glucose, glibenclamide or 3-isobutyl-1-methylxanthine, suggesting that protein kinase C activation, Ca2+ mobilization and cyclic AMP accumulation are all needed for full secretory response of mouse islets. Spermidine (5 mM) and spermine (1.5 mM) at concentrations found in islets inhibited protein kinase C stimulated by TPA + phosphatidylserine by 55% and 45% respectively. Putrescine (0.5 mM) was without effect, but inhibited the enzyme at higher concentrations (2-10 mM). Inhibition of protein kinase C by polyamines showed competition with Ca2+, and Ca2+ influx in response to glucose or glibenclamide prevented inhibition of insulin secretion by exogenous polyamines at concentrations where they did not affect glucose oxidation. It is suggested that inhibition of protein kinase C by polyamines may be of significance for regulation of insulin secretion in vivo and that Ca2+ influx may function by displacing inhibitory polyamines bound to phosphatidylserine in membranes.

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