The role of adenosine 3′:5′-cyclic monophosphate in the regulation of insulin release by isolated rat islets of Langerhans

Montague, W.; Cook, Jason R.

doi:10.1042/bj1220115

Cited by 165 publications

(98 citation statements)

References 19 publications

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“…Experiments with theophylline, which elevates islet cyclic AMP levels by inhibiting cyclic nucleotide phosphodiesterase [18], did not produce any evidence that the generation of cyclic AMP can induce a primed state in the B cell. Others [13] have shown that the enhanced secretion of insulin which occurs after glucose priming is not accompanied by a simultaneous increase in islet cyclic AMP formation.…”

Section: Discussionmentioning

confidence: 84%

The priming effect of glucose on insulin secretion from isolated islets of Langerhans

Ashby

Shirling

1981

Diabetologia

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Summary. Biphasic insulin secretion from perifused rat islets of Langerhans was enhanced if islets had previously been stimulated with glucose 16.6 mmol/1. The priming effect of glucose was reduced if mannoheptulose (16.6 mmol/1), deuterium oxide (D20; 98% v/v) or adrenaline (10 ~tmol/l) was included in the medium during the initial stimulation period, or if Calcium was omitted. Glyceraldehyde (16.6 mmol/1) but not theophylline (5 mmol/1) could substitute for glucose during the initial stimulation and make islets more responsive to subsequent stimulation. The results suggest that the priming effect of glucose on insulin secretion may be related to 1) glucose metabolism and 2) Ca fluxes in the B cell and the consequent activation of the microtubular system. Neither the generation of intracellular cyclic AMP nor the release of insulin per se appears to be involved in the priming process.Key words: Biphasic insulin secretion, perifused islets, glucose priming, mannoheptulose, glyceraldehyde, calcium, deuterium oxide, cyclic AMP, adrenaline.Acute exposure of the rat pancreatic B cell to glucose leads to biphasic secretion which is characterised by a short-lived burst of insulin release (phase 1) followed by a slower progressive rise in the secretory rate known as phase 2 [1][2][3][4]. Studies in vivo in man [5] and in vitro with the perfused rat pancreas [6] and perifused islets of Langerhans [7] have shown that a short period of glucose stimulation may also potentiate the secretory response of the B cell to a second pulse of glucose given shortly afterwards. Although it has been suggested that this effect occurs only if the concentration of glucose present during the initial stimulation period is in excess of approximately 14 mmol/1 in man [5] or 11 mmol/1 in perifused rat islets [7], the biochemical mechanisms mediating this phenomenon are poorly understood. In the present study the possible roles of 1) glucose metabolism 2) calcium and the microtubular system, and 3) cyclic AMP have been examined. The experiments were carried out using perifused rat islets of Langerhans. Materials and Methods Isolation and Perifusion of Islets of LangerhansMale Wister albino rats weighing approximately 200 g were fed ad libitum on a standard laboratory diet containing 48% carbohydrate, 21.3% protein and 3.4% fat. Islets were isolated by collagenase digestion [8]. The medium used for extraction and subsequent experiments was a bicarbonate-buffered salt solution with the following ionic composition: Na + 141; K + 5.9; Ca 2+ 2.5; Mg 2+ 1.2; PO~-1.2; CI-101 and HCO-3 24.9mmol/1; pH 7.4. The medium was supplemented with the sodium salts of glutamic, lactic and fumaric acids at a concentration of 5 rnmol/l [9]. The gas phase was O2:CO2 (95:5). The calcium concentration of 'calcium-free' media was 0.03mmol/1 as determined by atomic absorption spectrophotometry. When islets were exposed to deuterium oxide (D20) the ionic composition of the medium was unchanged but D20 replaced H20 to give a final concentration of 98% (v/v). The pH was ad...

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Section: Discussionmentioning

confidence: 84%

The priming effect of glucose on insulin secretion from isolated islets of Langerhans

Ashby

Shirling

1981

Diabetologia

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“…Ultrasonication of the incubate was followed by a centrifugation step, when acid-precipitated protein was spun down. Supernatants were chromatographed on Dowex 50 [8], lyophilised, and then dissolved in Tris buffer (50 mM; pH 7.4). Samples were taken for estimation of loss of cyclic AMP during the purification procedure.…”

Section: Methodsmentioning

confidence: 99%

Kinetics and dose—response characteristics of adenosine 3′,5′‐monophosphate production by isolated rat adrenal cells stimulated with adrenocorticotrophic hormone

1972

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“…First, glycogen accumulates in B-cells exposed for a sufficient time to high concentrations of glucose (Lazarow, 1963). Secondly, theophylline is known to increase the concentration of cyclic AMP in pancreatic endocrine cells (Charles et al, 1973;Montague & Cook, 1971;Turtle & Kipnis, 1967) and, in turn, cyclic AMP is reported to stimulate glycogenolysis in islet tissue (Hellman & Idahl, 1970).…”

Section: Discussionmentioning

confidence: 99%

The stimulus-secretion coupling of glucose-induced insulin release. Insulin release due to glycogenolysis in glucose-deprived islets

Malaisse¹,

Sener²,

Koser³

et al. 1977

Biochemical Journal

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1. When pancreatic islets are preincubated for 20h in the presence of glucose (83.3 mM) and thereafter transferred to a glucose-free medium, theophylline (1.4mM) provokes a dramatic stimulation of insulin release. This phenomenon does not occur when the islets are preincubated for either 20h at low glucose concentration (5.6mM) or only 30min at the high glucose concentration (83.3mM). 2. The insulinotropic action of theophylline cannot be attributed to contamination of the islets with exogenous glucose and is not suppressed by mannoheptulose. 3. The secretory response to theophylline is an immediate phenomenon, but disappears after 60min of exposure to the drug. 4. The release of insulin evoked by theophylline is abolished in calcium-depleted media containing EGTA. Theophylline enhances the net uptake of 45Ca by the islets. 5. Glycogen accumulates in the islets during the preincubation period, as judged by both ultrastructural and biochemical criteria. Theophylline significantly increases the rate of glycogenolysis during the final incubation in the glucose-free medium. 6. The theophylline-induced increase in glycogenolysis coincides with a higher rate of both lactate output and oxidation of endogenous 14C-labelled substrates. 7. These data suggest that stimulation of glycolysis from endogenous stores of glycogen is sufficient to provoke insulin release even in glucose-deprived islets, as if the binding of extracellular glucose to hypothetical plasmamembrane glucoreceptors is not an essential feature of the stimulus-secretion coupling process.The relative insulinotropic potency of different sugars closely parallels their ability to undergo glycolysis in pancreatic islets (for review, see Malaisse, 1977). However, the possible relevance of glycolysis to the process of glucose recognition by the B-cell is obscured by the fact that at the same time the sugar is present in the extracellular milieu and metabolized in the islet cells. Thus, under such conditions, it is difficult to distinguish between the respective roles of glucose binding to hypothetical membrane receptors, glucose transport across the plasma membrane and glucose metabolism as possible determinants of the secretory response.

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The role of adenosine 3′:5′-cyclic monophosphate in the regulation of insulin release by isolated rat islets of Langerhans

Cited by 165 publications

References 19 publications

The priming effect of glucose on insulin secretion from isolated islets of Langerhans

The priming effect of glucose on insulin secretion from isolated islets of Langerhans

Kinetics and dose—response characteristics of adenosine 3′,5′‐monophosphate production by isolated rat adrenal cells stimulated with adrenocorticotrophic hormone

The stimulus-secretion coupling of glucose-induced insulin release. Insulin release due to glycogenolysis in glucose-deprived islets

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