Insulin release and cyclic AMP accumulation in response to glucose in pancreatic islets of fed and starved rats.

Rabinovitch, Alex; Grill, Valdemar; Renold, Albert E.; Cerasi, Erol

doi:10.1172/jci108574

Cited by 42 publications

(24 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It therefore seems unlikely that the defect of insulin secretion in Acomys is caused exclusively by a deficient islet cyclic AMP metabolism. In contrast to the effects of IBMX, the timecourses of the glucose-induced cyclic AMP and insulin responses were qualitatively similar in the sense that stimulation was delayed for both variables in comparison with other species [19,20]. In islets from other species a close association between glucoseinduced effects on the two parameters has been documented under different experimental conditions [8,11,19,21].…”

Section: Discussionmentioning

confidence: 85%

The metabolism of cyclic AMP and glucose in isolated islets from Acomys cahirinus

Grill

Cerasi

1979

Diabetologia

View full text Add to dashboard Cite

Summary. Glucose-induced cyclic (3H) AMP accumulation, insulin secretory responses and the metabolism of glucose were studied in pancreatic islets from Acomys cahirinus. 27.7 mmol/1 of glucose stimulated neither islet cyclic (3H) AMP accumulation nor insulin release during the first 5 min of incubation. Stimulation by glucose of cyclic (3H) AMP was observed after 15 min of incubation and insulin release was markedly stimulated between 15 and 30 min. The utilization of glucose, measured as the production of (3H)20-from (5 -3H) glucose was stimulated by glucose after 10 min and proceeded at an apparently linear rate during a 20 min incubation period. In incubations of 5 min, glibenclamide, glucagon or chloromercuribenzene-p-sulphonic acid failed to stimulate islet cyclic (3H) AMP accumulation. 3-isobutyl-l-methylxanthine in a concentration of 1.0 mmol/1 was the only agent tested that elevated rapidly (1 min) islet cyclic (3H) AMP. None of the agents tested elicited an insulin secretory response in 5 rain incubations. It is concluded that 1) no gross defect is apparent in the utilization of glucose by Acomys islets, 2) the secretory derangement of the Acomys is associated with a delayed cyclic AMP response to glucose, 3) however a decreased level of cyclic AMP cannot be the sole explanation for the delayed insulin secretion in the Acomys.

show abstract

Section: Discussionmentioning

confidence: 85%

The metabolism of cyclic AMP and glucose in isolated islets from Acomys cahirinus

Grill

Cerasi

1979

Diabetologia

View full text Add to dashboard Cite

show abstract

“…As the culture period is extended, the rapid [Ca 2ϩ ] i oscillations disappear in favor of the slow ones, which also disappear after prolonged culture (31). The glucose concentration during culture is also decisive for the [Ca 2ϩ ] i oscillatory pattern (26 (35)(36)(37)(38). Indeed, when the content of cAMP was increased in the isolated islet, the regular electrical activity was promoted (39) and the slow [Ca 2ϩ ] i oscillations were replaced by the rapid oscillatory pattern (15,29).…”

Section: In Vitro Oscillations Of Islet Membrane Potential and [Ca 2؉mentioning

confidence: 99%

Role of Oscillations in Membrane Potential, Cytoplasmic Ca2+, and Metabolism for Plasma Insulin Oscillations

Bergsten

2002

Diabetes

View full text Add to dashboard Cite

(1,2). The frequency of the insulin pulses is important for the action of the hormone. Significantly less insulin is required when administered in a pulsatile fashion rather than as a bolus injection (3-7), which may result in different expression of the insulin receptor on target tissue (8). Indeed, a contributing cause to the glucose intolerance in type 2 diabetes may be related to the loss of the regular accentuated plasma insulin oscillations (9,10), which could aggravate insulin resistance by receptor downregulation.The oscillatory behavior seems to be intrinsic of the ␤-cell. Oscillations in the ␤-cell membrane potential, cytoplasmic Ca 2ϩ concentration ([Ca 2ϩ ] i ), and metabolism, with similar frequencies as the plasma insulin oscillations, have been described and suggested to be responsible for the pulsatile release of insulin (11-19). However, observations and conclusions made from experiments with isolated ␤-cells or islets do not necessarily translate into the in vivo situation. When evaluating the possible effects of oscillatory membrane potential, [Ca 2ϩ ] i , and metabolism on plasma insulin oscillations, oscillatory activities with different frequencies have to be considered. In this context, the oscillatory activity with a frequency of 2-7 oscillations (osc) per minute and that with a frequency of 0.2-0.4 osc/min will be discussed. Experimental observations of these rapid and slow islet oscillatory activities in vivo and in vitro are reviewed, together with an in vivo model of the ␤-cell, where the role of the oscillatory activities in membrane potential, [Ca 2ϩ ] i , and metabolism for the generation of plasma insulin oscillations are presented and discussed. IN VITRO OSCILLATIONS OF ISLET MEMBRANE POTENTIAL AND [Ca 2؉ ] iRapid oscillations in membrane potential and [Ca 2ϩ ] i (2-7 osc/min) have been observed and characterized in the isolated islet (14,15,20 -29). The membrane potential measurements consist of "slow waves," which are periods of depolarization when accumulations of action potentials ("bursts") promote influx of Ca 2ϩ , interspersed with periods of hyperpolarization, when no Ca 2ϩ influx is present. These slow waves give rise to the rapid oscillations in [Ca 2ϩ ] i . The glucose concentration affects both the duration of the bursts and the time relationship between periods of depolarization and hyperpolarization, i.e., the frequency of the slow waves (30).Slow oscillations (0.2-0.4 osc/min) in [Ca 2ϩ ] i (15,23,26 -28,31) and in membrane potential activity (32-34) have been recorded and characterized in the isolated islet. The frequency of these oscillations is not affected by the glucose concentration (23,27). The slow oscillations of [Ca 2ϩ ] i are primarily observed in cultured islets. As the culture period is extended, the rapid [Ca 2ϩ ] i oscillations disappear in favor of the slow ones, which also disappear after prolonged culture (31). The glucose concentration during culture is also decisive for the [Ca 2ϩ ] i oscillatory pattern (26). Although a low...

show abstract

“…This concentration of the phosphodiesterase inhibitor is known to increase cAMP levels several-fold and stimulate insulin secretion mode¬ rately (Rabinovitch et al 1976 (Table 3). …”

Section: Reversibility Ofbinding In Experiments Where Binding Incubatmentioning

confidence: 99%

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

Grill

Fak

1985

Acta Endocrinologica

View full text Add to dashboard Cite

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 \g=m\mtrifluoroperazine 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. The parasympathetic nervous system exerts an important influence on insulin secretion. Cephalic phase insulin secretion may thus be mediated to a major part by vagai stimulation ; its absence leads to delayed insulin secretion out of phase with mealinduced hyperglycaemia (Trimble et al. 1981). The receptors mediating the cholinergic effect are muscarinic in nature since acetylcholine-induced insu¬ lin secretion is readily blocked by atropine (Froh¬ man et al. 1967).To gain further insight into mechanisms behind acetylcholine-induced insulin release, we previous¬ ly studied binding of [3H]methylscopolamine to rat pancreatic islets. A high-affinity, rapid and specific binding of the muscarinic antagonist could be demonstrated (Grill & Östenson 1983). Half-maxi¬ mal inhibition of acethylcholine-induced release by methylscopolamine occurred at concentrations which were not lower than those causing halfmaximal displacement of label, suggesting that the binding parameter measured reflected an initial step in acetylcholine-induced insulin secretion.The aim of the present study was to gain further insight into islet regulation of muscarinic receptor binding and its role for insulin release. To this end we have investigated the effects on binding of factors of importance for insulin release such as the functional state of membrane thiol groups, per¬ turbations in cyclic AMP and calcium levels as well as changes in glucose metabolism. Additionally the dissociation of [3H]methylscopolamine was studied in order to further validate our procedure for measuring binding. Material and Methods Material and animah[3H]methylscopolamine chloride (S.A. 85 Ci/mmol) and [14C]sucrose (S.A. 673 mCi/mmol) was obtained from New England Nuclear (Dreieichenhain, FRG). Unlabel¬ led methylscopolamine nitrate was from Pharmacia, Uppsala, Sweden. Acetylcholine chloride, p-chloromerc...

show abstract

Insulin release and cyclic AMP accumulation in response to glucose in pancreatic islets of fed and starved rats.

Cited by 42 publications

References 36 publications

The metabolism of cyclic AMP and glucose in isolated islets from Acomys cahirinus

The metabolism of cyclic AMP and glucose in isolated islets from Acomys cahirinus

Role of Oscillations in Membrane Potential, Cytoplasmic Ca2+, and Metabolism for Plasma Insulin Oscillations

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

Contact Info

Product

Resources

About