Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To clarify whether the effect of sulfonylurea on glucagon secretion is directly on the pancreatic A cell, we examined changes produced by gliclazide in glucagon (IRG), insulin (IRI) and somatostatin (IRS) release from the isolated perfused rat pancreas. Under 5 mM glucose infusion, IRI and IRS were increased by gliclazide in a dose-dependent manner, but IRG was unchanged. When 20 mM arginine was infused to stimulate glucagon secretion, both IRI and IRG increased markedly in a biphasic fashion and IRS increased slightly. The administration of gliclazide at the time of second phase response of IRG, IRI and IRS increased further and IRG decreased at every dose used. Insulin administration to the control and streptozotocin-treated rat pancreas did not change arginine-induced IRG secretion. Gliclazide-induced glucagon suppression was also observed in streptozotocin-diabetic rat pancreas. The amount of administered somatostatin required for inhibiting glucagon secretion was higher than the maximal level obtained from endogenous secretion of somatostatin after gliclazide. Neither cysteamine treatment alone (somatostatin-depleted) nor combined with streptozotocin-treatment (combined depletion of somatostatin and insulin) changed gliclazide-induced glucagon suppression. Thus, it is concluded that suppression of glucagon is induced by sulfonylurea itself.
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PMID:Gliclazide directly suppresses arginine-induced glucagon secretion. 798 45

The mechanism of the hypoglycemic action of gliclazide was evaluated in 17 diet-treated non-insulin-dependent diabetes mellitus (NIDDM) patients. In study A, five patients received a 240-minute glucose infusion along with [3-3H]glucose infusion. In study B, seven patients received a 240-minute isoglycemic insulin clamp along with [3-3H]glucose infusion. And in study C, five patients received a somatostatin infusion with basal replacing doses of insulin and glucagon. The three studies (A, B, and C) were repeated twice. Gliclazide (240 mg orally) was administered on one occasion, and placebo was given on the second occasion. Basal hepatic glucose production (HGP) and utilization and plasma glucose, insulin, C-peptide, glucagon, and free fatty acid (FFA) concentrations were similar before administration of gliclazide and placebo. In study A, plasma glucose, its incremental area, and HGP were reduced by gliclazide administration (all P < .05), but glucose utilization was not significantly affected. The increase in plasma insulin and C-peptide concentrations was similar with gliclazide and placebo, although the plasma insulin to glucose ratio was increased with gliclazide. HGP decremental area was correlated with the reduction in plasma glucose incremental area (r = -.63, P < .05). In study B, gliclazide administration produced a larger suppression of HGP, but the overall rate of glucose utilization was not different in the two studies. In study C, plasma glucose concentration and HGP progressively decreased in both studies, without a difference between gliclazide and placebo. These results suggest that under conditions of hyperglycemia and hyperinsulinemia gliclazide elicits a larger suppression of HGP.
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PMID:Gliclazide potentiates suppression of hepatic glucose production in non-insulin-dependent diabetic patients. 884 72

Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of gliclazide or was secondary to the paracrine effect of released somatostatin. To eliminate the paracrine effects of somatostatin, we first perfused isolated rat pancreata with a medium supplemented with 23% of the standard calcium content. Second, we perifused isolated rat islets with a novel and highly specific antagonist of type 2 somatostatin receptor, DC-41-33 (2 micro mol/l), which fully antagonizes the suppressive somatostatin effect on rat A cells. Gliclazide (30 micro mol/l) inhibited glucagon release by 54% in the perfusion experiments, whereas the somatostatin response was nearly abolished. In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell.
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PMID:Gliclazide directly inhibits arginine-induced glucagon release. 1247 79