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.

Demonstration of glucose inhibition of insulin release in the presence of diazoxide

1987 ◽  
Vol 115 (2) ◽  
pp. 170-174 ◽  
Author(s):  
Peter Bergsten ◽  
Bo Hellman
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Β Cell ◽  
Glucose Stimulation ◽  
Inhibitory Component ◽  
Glucose Inhibition ◽  
Stimulation Of

Abstract. β-Cell-rich pancreatic islets from ob/ob mice were taken for measurements of insulin release in response to glucose after culture in RPMI 1640 medium. The stimulatory effect of 20 mmol/l glucose was converted into an inhibition when the medium was supplemented with 400 μmol/l diazoxide. Glucose inhibition of insulin release was observed when the islets had been cultured in the presence of 1 or 20 mmol/l glucose in media either containing or lacking Ca2+. The data provide further evidence for an inhibitory component in the action of glucose on insulin release, suggesting that glucose stimulation of the Ca2+ efflux is essential for the appearance of this inhibition.

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.

Sustained exposure of toxically damaged mouse pancreatic islets to high glucose does not increase β-cell dysfunction

1989 ◽  
Vol 123 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D. L. Eizirik ◽  
S. Sandler
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
High Glucose ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Stimulation ◽  
Cell Dysfunction ◽  
Mouse Pancreatic Islets ◽  
Insulin Secretory Response

ABSTRACT The aim of this study was to clarify whether prolonged in-vitro exposure of either normal or damaged β cells to a high glucose environment can be toxic to these cells. For this purpose NMRI mice were injected intravenously with a diabetogenic dose of streptozotocin (SZ; 160 mg/kg) or vehicle alone (controls). Their islets were isolated 15 min after the injection and subsequently maintained in culture for 21 days in the presence of 11·1 or 28 mmol glucose/l. After this period, during acute glucose stimulation, the control islets showed a marked increase in their insulin release in response to a high glucose stimulus. In the SZ-exposed islets there was a decrease in DNA and insulin contents, and a deficient insulin secretory response to glucose. However, in the SZ-damaged islets as well as in the control islets, culture with 28 mmol glucose/l compared with 11·1 mmol glucose/l did not impair islet retrieval after culture, islet DNA content or glucose-induced insulin release. Thus, the degree of damage was similar in the SZ-treated islets cultured at the two concentrations of glucose. These results suggest that glucose is not toxic to normal or damaged mouse pancreatic islets over a prolonged period in tissue culture. Journal of Endocrinology (1989) 123, 47–51

Interactions between magnesium and calcium in beta-cell-rich pancreatic islets

1983 ◽  
Vol 244 (6) ◽  
pp. E541-E547 ◽  
Author(s):  
P. O. Berggren ◽  
P. Bergsten ◽  
E. Gylfe ◽  
R. Larsson ◽  
B. Hellman
Keyword(s):  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Ionic Composition ◽  
Intracellular Magnesium ◽  
Glucose Inhibition ◽  
Outward Transport ◽  
Voltage Dependent ◽  
High Concentrations ◽  
45Ca Efflux

Calcium-magnesium interactions, total amounts of intracellular magnesium, and insulin release were studied in beta-cell-rich pancreatic islets from ob/ob mice. Mg2+ inhibited the uptake of intracellular 45Ca and insulin release induced by glucose or high concentrations of potassium. Omission of Mg2+ from a Ca2+-deficient medium resulted in an increased efflux of 45Ca, whereas the characteristic glucose inhibition of the efflux was diminished. After addition of Mg2+ to a Mg2+-depleted medium, the glucose-stimulated 45Ca efflux was markedly reduced. Mg2+ inhibited the basal efflux of 45Ca, and this effect was preceded by a transient stimulation. Ca2+ but not Mg2+ stimulated 45Ca efflux in a medium depleted of Ca2+, Mg2+, and Na+. The data indicate that Mg2+ interferes with Ca2+ entry through voltage-dependent Ca2+ channels. Mg2+ may also inhibit the outward transport of Ca2+ from the cells at a site different from the Na+-Ca2+ countertransport mechanism. The total amount of intracellular magnesium remained unaffected by glucose and was not changed unless the ionic composition of the mediums were changed grossly. Under physiological conditions it is therefore unlikely that fluctuations in the intracellular Mg2+ concentration are part of the mechanism by which the functionally important Ca2+ is regulated.

THE EFFECT OF FASTING AND SELECTIVE RE-FEEDING ON INSULIN RELEASE IN THE RAT

1973 ◽  
Vol 72 (1) ◽  
pp. 46-53 ◽  
Author(s):  
D. S. Turner ◽  
D. A. B. Young
Keyword(s):  
Insulin Release ◽  
Acute Effect ◽  
Secretory Response ◽  
Release Mechanism ◽  
Β Cell ◽  
Intestinal Hormones ◽  
Intravenous Glucose ◽  
Glucose Ingestion ◽  
Glucose Test ◽  
Insulin Secretory Response

ABSTRACT The insulin secretory response in the rat to intravenous glucose was found to be greatly impaired by fasting for three days, whereas that to orally administered glucose was not significantly affected. Rats fasted for two days were given either protein or starch pellets for six hours, and then fasted for a further eighteen hours before the intravenous glucose test. The protein pre-feeding failed to affect significantly the subsequent insulin secretory response to intravenous glucose, whereas starch prefeeding greatly enhanced it. It is suggested that intestinal hormones released by glucose ingestion may exert not only an acute effect on insulin release, but also a 'priming' effect on the insulin release mechanism of the β cell, which enables it to respond to the subsequent stimulus of glucose alone.

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