Gliclazide Directly Inhibits Arginine-Induced Glucagon Release

Čejvan, Kenan; Coy, David H.; Holst, Jens J.; Cerasi, Erol; Efendić, Suad

doi:10.2337/diabetes.51.2007.s381

Cited by 17 publications

(10 citation statements)

References 37 publications

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“…While it is well established that hyperglycemia suppresses glucagon secretion strongly, the effect of sulfonylurea on glucagon secretion is controversial and reported to be unaffected (17), stimulated (38), inhibited (39), and influenced differently depending on the prevailing glucose and drug concentration and presence of paracrine effectors (38,40,41). We observed that during infusion with tolbutamide alone, glucagon secretion did not rise in the presence of 3 mmol/l glucose.…”

Section: Discussionmentioning

confidence: 50%

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

2007

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Section: Discussionmentioning

confidence: 50%

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

2007

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“…However, exposure of islets to glucose or sulfonylureas activates both ␤-cells and ␦-cells (1,34), which initiates an insulin secretory response and simultaneously causes the local release of SST to limit that response. Similarly, the stimulation of glucagon secretion by arginine is accompanied by both the activation of ␦-cells (33) and the intraislet release of SST to limit the ␣-cell secretory response. In this way, both in vitro and in vivo results are consistent with ␦-cell SST exerting an inhibitory paracrine influence on islet ␣-and ␤-cells.…”

Section: Diabetes Vol 58 February 2009mentioning

confidence: 99%

Somatostatin Secreted by Islet δ-Cells Fulfills Multiple Roles as a Paracrine Regulator of Islet Function

Hauge-Evans

King

Carmignac³

et al. 2009

Diabetes

280

263

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OBJECTIVE-Somatostatin (SST) is secreted by islet ␦-cells and by extraislet neuroendocrine cells. SST receptors have been identified on ␣-and ␤-cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating ␣-and ␤-cell function. However, the specific intraislet function of ␦-cell SST remains uncertain. We have used Sst Ϫ/Ϫ mice to investigate the role of ␦-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo. RESEARCH DESIGN AND METHODS-Islet morphology wasassessed by histological analysis. Hormone levels were measured by radioimmunoassay in control and Sst Ϫ/Ϫ mice in vivo and from isolated islets in vitro. RESULTS-Islet size and organization did not differ between SstϪ/Ϫ and control islets, nor did islet glucagon or insulin content. Sst Ϫ/Ϫ mice showed enhanced insulin and glucagon secretory responses in vivo. In vitro stimulus-induced insulin and glucagon secretion was enhanced from perifused Sst Ϫ/Ϫ islets compared with control islets and was inhibited by exogenous SST in Sst Ϫ/Ϫ but not control islets. No difference in the switch-off rate of glucose-stimulated insulin secretion was observed between genotypes, but the cholinergic agonist carbamylcholine enhanced glucose-induced insulin secretion to a lesser extent in Sst Ϫ/Ϫ islets compared with controls. Glucose suppressed glucagon secretion from control but not Sst Ϫ/Ϫ islets.CONCLUSIONS-We suggest that ␦-cell SST exerts a tonic inhibitory influence on insulin and glucagon secretion, which may facilitate the islet response to cholinergic activation. In addition, ␦-cell SST is implicated in the nutrient-induced suppression of glucagon secretion. Diabetes 58:403-411, 2009

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“…Current knowledge of the regulation of somatostatin secretion is limited, but the available evidence suggests that delta cells respond similarly to beta cells. Accordingly, some studies have demonstrated that glucose stimulates both insulin and somatostatin release [11,12], as do membrane-depolarising agents such as arginine and sulfonylureas [11,[13][14][15][16], as well as the incretin, glucagon-like peptide 1 (GLP-1) [15][16][17][18][19][20]. These observations may reflect similar stimulus-response coupling mechanisms in beta and delta cells, but they could also suggest that delta cell secretory responses are indirectly regulated in a paracrine manner by insulin released from beta cells.…”

Section: Introductionmentioning

confidence: 99%

Delta cell secretory responses to insulin secretagogues are not mediated indirectly by insulin

et al. 2012

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Aims/hypothesis Somatostatin from islet delta cells inhibits insulin and glucagon secretion, but knowledge of the regulation of pancreatic somatostatin release is limited. Some insulin secretagogues stimulate somatostatin secretion, and here we investigated whether delta cell secretory responses are indirectly regulated in a paracrine manner by insulin released from beta cells. Methods Hormone release from static incubations of primary mouse islets or somatostatin-secreting TGP52 cells was measured by RIA. mRNA expression was assessed by RT-PCR. Results Glucose and a range of other physiological and pharmacological agents stimulated insulin and somatostatin release, and insulin receptor mRNA was expressed in islets, MIN6 beta cells and TGP52 cells. However, exogenous insulin did not modulate basal or glucose-induced somatostatin secretion from islets, nor did pre-incubation with an antibody against the insulin receptor or with the insulin receptor tyrosine kinase inhibitor, HNMPA(AM) 3 . Glucose and tolbutamide stimulated somatostatin release from TGP52 cells, whereas a range of receptor-operating agents had no effect, the latter being consistent with a lack of corresponding receptor mRNA expression in these cells. Parasympathetic activation stimulated insulin, but inhibited somatostatin release from mouse islets in accordance with differences in muscarinic receptor mRNA expression in islets, MIN6 and TGP52 cells. The inhibitory effect on somatostatin secretion was reversed by pertussis toxin or the muscarinic receptor 2 antagonist, methoctramine. Conclusions/interpretations A number of insulin secretagogues have analogous effects on insulin and somatostatin release, but this similarity of response is not mediated by an indirect, paracrine action of insulin on delta cells.

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Gliclazide Directly Inhibits Arginine-Induced Glucagon Release

Cited by 17 publications

References 37 publications

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

Somatostatin Secreted by Islet δ-Cells Fulfills Multiple Roles as a Paracrine Regulator of Islet Function

Delta cell secretory responses to insulin secretagogues are not mediated indirectly by insulin

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