Effects of starvation on oxidative metabolism and insulin release by isolated mouse pancreatic islets

1982 ◽  
Vol 101 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Michael Welsh ◽  
Arne Andersson
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Oxidative Metabolism ◽  
Oxidation Rate ◽  
Insulin Response ◽  
Leucine Oxidation ◽  
Oxidation Rates ◽  
Impaired Insulin ◽  
Mouse Pancreatic Islets ◽  
Insulin Response To Glucose

Abstract. Pancreatic islets were isolated from either 60-h-starved or fed mice and subsequently incubated in order to determine the insulin release in response to various secretagogues, rates of glucose, leucine or glutamine oxidation or the acetoacetate production from leucine. It was found that in contrast to findings with islets isolated from fed mice 16.7 mm glucose, 10 mM leucine and 10 mm α-ketoisocaproic acid did not stimulate the insulin release of islets isolated from starved mice. Moreover, the insulin release in response to leucine plus glutamine or glucose plus glutamine was decreased after starvation although these values were higher than those obtained for glutamine addition alone. Theophylline, however, restored partly the impaired insulin response to glucose and completely that to leucine or α-ketoisocaproic acid. Starvation was found to inhibit the islet glucose oxidation rate but the addition of theophylline was without effect irrespective of whether the islets were prepared from fed or starved mice. On the contrary, islet leucine oxidation was increased after starvation and again theophylline did not affect the islet leucine oxidation rate. Likewise, the islet acetoacetate production was increased after starvation. The glutamine oxidation rates were not affected by starvation, either when tested alone or together with glucose or leucine. It is concluded that although the starvation-induced impairment of glucose-stimulated insulin release may well be explained by an influence on the oxidative metabolism other factors are also involved as regards leucine-stimulated insulin release.

Persistent impairment of the insulin response to glucose both in vivo and in vitro after streptozotocin exposure: Studies with grafted pancreatic islets and islets maintained in culture

1989 ◽  
Vol 121 (6) ◽  
pp. 849-856 ◽  
Author(s):  
Décio L. Eizirik ◽  
Stellan Sandler ◽  
Olle Korsgren ◽  
Leif Jansson ◽  
Arne Andersson
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Common Property ◽  
Insulin Response ◽  
Insulin Content ◽  
Functional Responses ◽  
Mouse Pancreatic Islets ◽  
Insulin Response To Glucose

Abstract. The functional responses of the pancreatic B-cells after cytotoxic damage are still largely unknown. Using in vitro models to clarify this issue, we have recently observed a preferential reduction of glucose-stimulated insulin production and release in mouse pancreatic islets maintained in culture after in vitro exposure to streptozotocin. In order to evaluate the relevance of these findings in vivo, two sets of experiments were performed. First, mouse pancreatic islets were exposed in vitro to 2.2 mmol/l streptozotocin or vehicle alone, cultured for 6 days, and finally grafted under the kidney capsule of normoglycemic nude mice. Two weeks after transplantation there was no difference in the total DNA and insulin content between the two groups of islet grafts, but the insulin concentration, as expressed per μg DNA, was decreased by 40% in the streptozotocin-treated islets. The insulin release of the grafts, during perfusion of the graft-bearing kidney in situ with 16.7 mmol/l glucose was diminished in the streptozotocin group, whilst perfusion with 16.7 mmol/l glucose plus 5 mmol/l theophylline was able partially to counteract the reduction in insulin release. In the second set of experiments, NMRI mice were injected iv with 160 mg/kg streptozotocin or vehicle alone, and their islets isolated 15 min after the injections. After 6 days in culture, there was no decrease in DNA, glucagon and somatostatin contents, but the insulin content was decreased by 40% in the streptozotocin exposed islets. These islets also showed a 60% decrease in the insulin response to glucose, which was partly counteracted by incubation with 16.7 mmol/1 glucose plus 5 mmol/l theophylline. These observations suggest that a defective response to glucose, in conjunction with a better response to non-nutrient secretagogues, may be a common property of pancreatic islets following toxin-induced disturbances.

Role of Ca2+ in impaired insulin release from islets of diabetic (C57BL/KsJ-db/db) mice

1980 ◽  
Vol 239 (2) ◽  
pp. E132-E138
Author(s):  
E. G. Siegel ◽  
C. B. Wollheim ◽  
G. W. Sharp ◽  
L. Herberg ◽  
A. E. Renold
Keyword(s):  
Tissue Culture ◽  
Beta Cell ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Insulin Response ◽  
Isolated Islets ◽  
Diabetic Mice ◽  
Impaired Insulin ◽  
Insulin Response To Glucose

The involvement of Ca2+ in the impaired insulin release of diabetic C57BL/KsJ-db/db mice was studied. Twenty-week-old severely hyperglycemic mice were compared to nondiabetic C57BL/KsJ mice as controls. Collagenase-isolated islets were maintained for 46 h in tissue culture allowing for equilibration at the same glucose concentration (8.3) mM). The insulin content of both types of islets was similar. In control islets preloaded during culture with 45Ca2+ glucose-induced insulin release was associated with increased 45Ca2+ effux. Islets from diabetic mice showed markedly reduced insulin response to glucose and a smaller increase in 45Ca2+ efflux. Because insulin release was strikingly potentiated by 3-isobutyl-1-methylxanthine (IBMX), even more than in control islets, there was no generalized release defect. In both types of islets, IBMX potentiation was accompanied by a further enhanced 45Ca2+ efflux, possibly suggesting that cAMP effects are associated with increased cytosol Ca2+% concentrations. As Ca2+ uptake was stimulated by glucose in both types of islets, a defect may lie in the mechanism by which glucose uses cellulr calcium to raise cytosol Ca2+ in the beta-cell of these diabetic mice.

Glucocorticoid increases glucose cycling and inhibits insulin release in pancreatic islets of ob/ob mice

1992 ◽  
Vol 263 (4) ◽  
pp. E663-E666 ◽  
Author(s):  
A. Khan ◽  
C. G. Ostenson ◽  
P. O. Berggren ◽  
S. Efendic
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Oxidation ◽  
Insulin Response ◽  
Dexamethasone Treatment ◽  
Short Term ◽  
Glucose Flux ◽  
Glucose Incorporation ◽  
Insulin Response To Glucose ◽  
Insulin Responsiveness

Normoglycemic ob/ob mice were treated for 24 or 48 h with either 25 micrograms/day of dexamethasone or saline. After an overnight fast, the animals were killed and pancreatic islets were incubated with 3H2O or [U-14C]glucose or [5-3H]glucose at 5.5 and 16.7 mM glucose. Incorporation of 3H from 3H2O into carbon 2 of medium glucose and the yield of 14CO2 from [U-14C]glucose and 3H2O from [5-3H]glucose were measured. Dexamethasone treatment for 48 h significantly increased the rate of dephosphorylation of glucose in islets both at 5.5 mM (24 vs. 16%) and 16.7 mM (56 vs. 36%) glucose, whereas glucose oxidation and utilization were unaffected. Dexamethasone treatment also inhibited insulin release by approximately 60% at 5.5 and 16.7 mM glucose, either in the presence or absence of 10 mM arginine, but had no effect when insulin release was stimulated by 1 mM 3-isobutyl-1-methylxanthine. Moreover, 24-h treatment with dexamethasone significantly increased glucose cycling at low and high glucose concentrations in the medium and inhibited insulin responsiveness to glucose and arginine. In conclusion, short-term dexamethasone treatment increases glucose flux through glucose-6-phosphatase in islets from ob/ob mice. This effect may contribute to the decreased insulin response to glucose and arginine found in animals treated with dexamethasone.

EFFECT OF SOMATOSTATIN ON BASAL AND GLUCOSE INDUCED INSULIN RELEASE IN FIVE PATIENTS WITH HYPERINSULINAEMIA

1976 ◽  
Vol 81 (2) ◽  
pp. 525-529 ◽  
Author(s):  
S. Efendić ◽  
P. E. Lins ◽  
G. Sigurdsson ◽  
B. Ivemark ◽  
P. O. Granberg ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Therapeutic Effect ◽  
Basal Insulin ◽  
Insulin Response ◽  
Inhibitory Effect ◽  
Maximal Response ◽  
Minor Response ◽  
Insulin Response To Glucose ◽  
A Minor

ABSTRACT Somatostatin in a dose of 490 μg over 90 min inhibited basal insulin release in one subject with hyperplasia of the pancreatic islets and in two with benign insulin secreting adenomas. These three subjects also showed a marked insulin response to glucose infusion. No inhibitory effect of somatostatin was observed in two patients with benign insulinomas who demonstrated only a minor response to glucose. In the patient with islet hyperplasia and in one of the adenoma patients, who had an exaggerated insulin response to glucose (maximal response 10–30 times the basal insulin value), somatostatin also suppressed glucose induced insulin release. Our data suggest a beneficial therapeutic effect of somatostatin in patients with spontaneous hyperinsulinism with a pronounced insulin response to glucose.

scholarly journals The possible mechanisms by which phanoside stimulates insulin secretion from rat islets

2007 ◽  
Vol 192 (2) ◽  
pp. 389-394 ◽  
Author(s):  
Nguyen Khanh Hoa ◽  
Åke Norberg ◽  
Rannar Sillard ◽  
Dao Van Phan ◽  
Nguyen Duy Thuan ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
B Cells ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Pertussis Toxin ◽  
Insulin Response ◽  
Gk Rat ◽  
Isolated Pancreatic Islets ◽  
Gk Rats ◽  
Rat Islets

We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3.3 and 16.7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 μM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3.3 mM glucose with 150 μM phanoside and 0.25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 μM phanoside alone. At 16.7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0.25 mM diazoxide (P<0.01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3.3 mM glucose but did not further increase the release at 16.7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3.3 mM glucose but decreased at 16.7 mM glucose (P<0.01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 μM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.

scholarly journals Long-term effects of glucose on insulin release and glucose oxidation by mouse pancreatic islets maintained in tissue culture

1974 ◽  
Vol 140 (3) ◽  
pp. 377-382 ◽  
Author(s):  
Arne Andersson
Keyword(s):  
Tissue Culture ◽  
B Cells ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
High Glucose ◽  
Glucose Concentration ◽  
Glucose Oxidation ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Mouse Pancreatic Islets

Rates of glucose oxidation and insulin release in response to a wide range of glucose concentrations were studied in short-term experiments in isolated mouse pancreatic islets maintained in tissue culture for 6 days at either a physiological glucose concentration (6.7mm) or at a high glucose concentration (28mm). The curves relating glucose oxidation or insulin release to the extracellular glucose concentration obtained with islets cultured in 6.7mm-glucose displayed a sigmoid shape similar to that observed for freshly isolated non-cultured islets. By contrast islets that had been cultured in 28mm-glucose showed a linear relationship between the rate of glucose oxidation and the extracellular glucose concentration up to about 8mm-glucose. The maximal oxidative rate was twice that of the non-cultured islets and the glucose concentration associated with the half-maximal rate considerably decreased. In islets cultured at 28mm-glucose there was only a small increase in the insulin release in response to glucose, probably due to a depletion of stored insulin in those B cells that had been cultured in a high-glucose medium. It is concluded that exposure of B cells for 6 days to a glucose concentration comparable with that found in diabetic individuals causes adaptive metabolic alterations rather than degeneration of these cells.

Prevalence of Diabetes-associated Antibodies and Impaired Insulin Response to Glucose in First Degree Relatives of Diabetic Patients

2006 ◽  
Vol 6 (2) ◽  
pp. 139-148
Author(s):  
Ebtissam M. Salah ◽  
Hesham El-Hafnawy . ◽  
Mona Anwar M. . ◽  
Samar M.E. Salem . ◽  
Mai M. Youssef . ◽  
...  
Keyword(s):  
Insulin Response ◽  
Diabetic Patients ◽  
First Degree Relatives ◽  
Impaired Insulin ◽  
Insulin Response To Glucose

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.

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