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 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.

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 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.

Glucose-induced pulsatile insulin release from single islets at stable and oscillatory cytoplasmic Ca2+

1998 ◽  
Vol 274 (5) ◽  
pp. E796-E800 ◽  
Author(s):  
Peter Bergsten
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Small Amplitude ◽  
Similar Frequency ◽  
Secretory Rate ◽  
Mouse Pancreatic Islets

The cytoplasmic Ca2+ concentration ([Ca2+]i) and insulin release were measured simultaneously in mouse pancreatic islets cultured overnight. [Ca2+]iwas 105 nM and insulin release 3 pmol ⋅ g−1 ⋅ s−1at 3 mM glucose. An increase to 7 mM glucose reduced [Ca2+]itransiently, whereas insulin release doubled and was pulsatile with a frequency of 0.47 min−1. [Ca2+]i oscillations with similar frequency appeared at 11 mM glucose associated with increased amplitude of the insulin oscillations, raising the secretory rate 10-fold. In the presence of 16 and 20 mM glucose [Ca2+]iwas >300 nM and showed no oscillations apart from two islets, which demonstrated [Ca2+]ioscillations with small amplitude at 16 mM glucose. Insulin release with maintained frequency increased by 46 and 31%, respectively. When the glucose concentration was increased from 3 to 11 mM, [Ca2+]idecreased with a nadir that appeared significantly earlier than when the glucose concentration was raised from 3 to 7 mM. Glucose-induced insulin release from the isolated islet is pulsatile both at stable and oscillatory [Ca2+]i, with changes in secretory rate caused by the sugar also when [Ca2+]iis unchanged.

scholarly journals Inosine-stimulated insulin release and metabolism of inosine in isolated mouse pancreatic islets

1976 ◽  
Vol 158 (2) ◽  
pp. 335-340 ◽  
Author(s):  
K Capito ◽  
C J Hedeskov
Keyword(s):  
Insulin Secretion ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Pancreatic Islets ◽  
Beta Cells ◽  
Insulin Release ◽  
Lactate Production ◽  
Islet Metabolism ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets

Inosine is a potent primary stimulus of insulin secretion from isolated mouse islets. The inosine-induced insulin secretion was totally depressed during starvation, but was completely restored by the addition of 5 mM-caffeine to the medium and partially restored by the addition of 5 mM-glucose. Mannoheptulose (3 mg/ml) potentiated the effect of 10 mM-inosine in islets from fed mice. The mechanism of the stimulatory effect of inosine was further investigated, and it was demonstrated that pancreatic islets contain a nucleoside phosphorylase capable of converting inosine into hypoxanthine and ribose 1-phosphate. Inosine at 10 mM concentration increased the lactate production and the content of ATP, glucose 6-phosphate (fructose 1,6-diphosphate + triose phosphates) and cyclic AMP in islets from fed mice. In islets from starved mice inosine-induced lactate production was decreased and no change in the concentration of cyclic AMP could be demonstrated, whereas the concentration of ATP and glucose 6-phosphate rose. Inosine (10 mM) induced a higher concentration of (fructose 1,6-diphosphate + triose phosphates) in islets from starved mice than in islets from fed mice suggesting that in starvation the activities of glyceraldehyde 3-phosphate dehydrogenase or other enzymes below this step in glycolysis are decreased. Formation of glucose from inosine was negligible. Inosine had no direct effect on adenylate cyclase activity in islet homogenates. The observed changes in insulin secretion and islet metabolism mimic what is seen when glucose and glyceraldehyde stimulate insulin secretion, and as neither ribose nor hypoxanthine-stimulated insulin release, the results are interpreted as supporting the substrate-site hypothesis for glucose-induced insulin secretion according to which glucose has to be metabolized in the beta-cells before secretion is initiated.

Pulsatile insulin secretion from isolated human pancreatic islets

Diabetes ◽  
1994 ◽  
Vol 43 (6) ◽  
pp. 827-830 ◽  
Author(s):  
P. Marchetti ◽  
D. W. Scharp ◽  
M. Mclear ◽  
R. Gingerich ◽  
E. Finke ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Human Pancreatic Islets ◽  
Pulsatile Insulin Secretion

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.

scholarly journals The effect of starvation on insulin secretion and glucose metabolism in mouse pancreatic islets

1974 ◽  
Vol 140 (3) ◽  
pp. 423-433 ◽  
Author(s):  
Carl J. Hedeskov ◽  
Kirsten Capito
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Glucose Utilization ◽  
Secretory Response ◽  
Secretory Process ◽  
Fed State ◽  
Lactate Output ◽  
Extracellular Glucose ◽  
Km Value

1. Rates of insulin secretion, glucose utilization, lactate output, incorporation of glucose into glycogen, contents of glucose 6-phosphate, fructose 1,6-diphosphate and ATP, and maximally extractable enzyme activities of hexokinase, high-Km glucose-phosphorylating activity (`glucokinase'), glucose 6-phosphatase and unspecific acid phosphatase were measured in isolated pancreatic islets from fed and 48-h-starved mice. 2. In the fed state insulin secretion from isolated islets was increased five- to six-fold when the extracellular glucose concentration was raised from 2.5mm to 16.7mm; 5mm-caffeine potentiated this effect. The secretory response to glucose of islets from mice starved for 48h was diminished at all glucose concentrations from 2.5mm up to approx. 40mm. Very high glucose concentrations (60mm and above) restored the secretory response to that found in the fed state, suggesting that the Km value for the overall secretory process had been increased (approx. fourfold) by starvation. Addition of 5mm-caffeine to islets from starved mice also restored the insulin secretory response to 2.5–16.7mm-glucose to normal values. 3. Extractable hexokinase, `glucokinase', glucose 6-phosphatase and unspecific phosphatase activities were not changed by starvation. 4. Glucose utilization and glycolysis (measured as the rate of formation of 3H2O from [5-3H]glucose over a 2h period) was decreased in islets from starved mice at all glucose concentrations up to approx. 55mm. At still higher glucose concentrations up to approx. 100mm, there was no difference between the fed and starved state, suggesting that the Km value for the rate-limiting glucose phosphorylation had been increased (approx. twofold) by starvation. Preparation of islets omitting substrates (glucose, pyruvate, fumarate and glutamate) from the medium during collagenase treatment lowered the glucose utilization measured subsequently at 16.7mm-glucose by 38 and 30% in islets from fed and starved mice respectively. Also the 2h lactate output by the islets at 16.7mm extracellular glucose was diminished by starvation. Incorporation of glucose into glycogen was extremely low, but the rate of incorporation was more than doubled by starvation. 5. After incubation for 30min at 16.7mm-glucose the content of glucose 6-phosphate was unchanged by starvation, that of ATP was increased and the concentration of (fructose 1,6-diphosphate plus triose phosphates) was decreased. 6. Possible mechanisms behind the correlated impairment in insulin secretion and islet glucose metabolism during starvation are discussed.

Sign in / Sign up

Export Citation Format

Share Document