Activation by glucose of adenyl cyclase in pancreatic islets of the rat

Grill, Valdemar; Cerasi, Erol

doi:10.1016/0014-5793(73)80218-2

Cited by 81 publications

(61 citation statements)

References 14 publications

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“…An early hypothesis proposed that cAMP is a prime mediator of glucose-stimulated insulin secretion (7,38). This hypothesis was supported by findings that glucose raises the islet content of cAMP (7,39,40).…”

Section: Discussionmentioning

confidence: 91%

“…Such a function is supported by studies showing that cAMP levels are increased in ␤-cells stimulated with glucose (6,7). Other studies, however, indicate that glucosestimulated insulin release occurs efficiently regardless of ␤-cell PKA activity (8,9), and it has been suggested that even though cAMP can elicit insulin secretion it may not be necessary for glucose-stimulated insulin release.…”

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confidence: 98%

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Important Role of Phosphodiesterase 3B for the Stimulatory Action of cAMP on Pancreatic β-Cell Exocytosis and Release of Insulin

Härndahl¹,

Jing²,

Ivarsson³

et al. 2002

Journal of Biological Chemistry

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Cyclic AMP potentiates glucose-stimulated insulin release and mediates the stimulatory effects of hormones such as glucagon-like peptide 1 (GLP-1) on pancreatic ␤-cells. By inhibition of cAMP-degrading phosphodiesterase (PDE) and, in particular, selective inhibition of PDE3 activity, stimulatory effects on insulin secretion have been observed. Molecular and functional information on ␤-cell PDE3 is, however, scarce. To provide such information, we have studied the specific effects of the PDE3B isoform by adenovirus-mediated overexpression. In rat islets and rat insulinoma cells, approximate 10-fold overexpression of PDE3B was accompanied by a 6 -8-fold increase in membrane-associated PDE3B activity. The cAMP concentration was significantly lowered in transduced cells (INS-1(832/13)), and insulin secretion in response to stimulation with high glucose (11.1 mM) was reduced by 40% (islets) and 50% (INS-1). Further, the ability of GLP-1 (100 nM) to augment glucose-stimulated insulin secretion was inhibited by ϳ30% (islets) and 70% (INS-1). Accordingly, when stimulating with cAMP, a substantial decrease (65%) in exocytotic capacity was demonstrated in patch-clamped single ␤-cells. In untransduced insulinoma cells, application of the PDE3-selective inhibitor OPC3911 (10 M) was shown to increase glucose-stimulated insulin release as well as cAMP-enhanced exocytosis. The findings suggest a significant role of PDE3B as an important regulator of insulin secretory processes.

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 98%

Important Role of Phosphodiesterase 3B for the Stimulatory Action of cAMP on Pancreatic β-Cell Exocytosis and Release of Insulin

Härndahl¹,

Jing²,

Ivarsson³

et al. 2002

Journal of Biological Chemistry

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“…Preparation and incubation of pancreatic islets were performed according to a recently reported technique [6].…”

Section: Methodsmentioning

confidence: 99%

Effect of somatostatin on glucose induced insulin release in isolated perfused rat pancreas and isolated rat pancreatic islets

1974

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“…It must be noted that while Delmeire and colleagues did not observe an increase in intracellular cAMP in response to glucose alone this is most likely due to their cell system which was primary β cells separated by FACS analysis. Isolated β cells are known to produce much lower levels of cAMP than whole islets (Schuit and Pipeleers, 1985) and increased glucose concentrations have been extensively demonstrated to increase cAMP accumulation in whole islets (Grill and Cerasi, 1973;Sharp, 1979). cAMP is the main mediator of GLP-1 agonist action on acute molecular events in insulin secretion in β cells and overexpression of the GLP-1R in a clonal β cell line leads to increased resting levels of cAMP (Montrose-Rafizadeh et al, 1997a).…”

Section: Stimulation Of Camp Productionmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

584

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Activation by glucose of adenyl cyclase in pancreatic islets of the rat

Cited by 81 publications

References 14 publications

Important Role of Phosphodiesterase 3B for the Stimulatory Action of cAMP on Pancreatic β-Cell Exocytosis and Release of Insulin

Important Role of Phosphodiesterase 3B for the Stimulatory Action of cAMP on Pancreatic β-Cell Exocytosis and Release of Insulin

Effect of somatostatin on glucose induced insulin release in isolated perfused rat pancreas and isolated rat pancreatic islets

Mechanisms of action of glucagon-like peptide 1 in the pancreas

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