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

The effects of sulfonylurea on glucagon secretion were characterized in the perfused rat pancreas using glibenclamide (1 microgram/ml) or tolazamide (10 micrograms/ml) in the presence of 3.3 mmol/l glucose. Glucagon release, which was unaffected by glibenclamide at 2.75 mmol/l calcium, was suppressed at 1.19 and 0.64 mmol/l but transiently stimulated at 0.25 mmol/l extracellular calcium. The insulinogenic effect of glibenclamide at 0.64 and 0.25 mmol/l calcium was enhanced by 35% and 89%, respectively, compared to the response at 2.75 mmol/l calcium. The stimulatory effect of the compound on somatostatin secretion, however, was lost at the lower calcium levels. The effects of tolazamide at 2.75 and 0.64 mmol/l calcium mimicked those of glibenclamide, thus indicating that our results with the latter compound may be representative for all sulfonylureas. In pancreata from insulin-deficient alloxan-diabetic rats, glibenclamide completely lost its inhibitory effect on glucagon release at 0.64 mmol/l calcium. Inhibition was not restored by adding insulin (25 U/l) to the perfusate. However, when diabetic rats had been treated with insulin for 6-7 days, glibenclamide suppressed glucagon release at low calcium levels in the absence of stimulated insulin and somatostatin release. It is concluded that, at low calcium concentrations, sulfonylureas suppress glucagon secretion by a direct action on the A cell and not through paracrine interactions by insulin and somatostatin. Prolonged insulin deficiency impairs the sulfonylurea action on glucagon secretion.
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PMID:Sulfonylurea-induced inhibition of glucagon secretion from the perfused rat pancreas: evidence for a direct, non-paracrine effect. 310 22

Hyperglycaemia may enhance insulin resistance typical of non-insulin dependent diabetes mellitus, as well as insulin dependent diabetes mellitus, and thus initiate a vicious pathogenetic cycle. We sought to test the hypothesis that reduction in chronic hyperglycaemia in the diabetic dog by methods that do not employ insulin may improve insulin resistance. We used the glucuretic agent phlorizin in dogs rendered chronically hyperglycaemic and diabetic by alloxan treatment. To analyse glucose disposition the euglycaemic clamp was performed. To minimize the role of counterregulatory influences that might be at play when glucose is reduced, the hyperglycaemic clamp with continuous somatostatin infusion was performed. Although phlorizin normalised plasma glucose in the diabetic dog and reduced plasma glucose in normal, non-diabetic dogs, insulin dependent glucose disposition rate did not improve. While phlorizin itself was associated with insulin resistance in the normal animals, the insulin resistance of diabetes mellitus was not further augmented. We conclude that phlorizin is associated with insulin resistance perhaps by a common pathway shared by chronic hyperglycaemia. Care must be taken when phlorizin is used as an agent to study glucose disposition.
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PMID:Antecedent chronic hyperglycaemia blocks phlorizin-induced insulin resistance in the dog. 338 20

The antiprotozoal drug pentamidine can be toxic to islet cells in vivo and in vitro. Rat islets were exposed to pentamidine (mesylate and isethionate salts) and six other structurally related diamidines. The beta-cell response to arginine + theophylline was suppressed by pentamidine (10(-2) mmol/l) while the glucagon and somatostatin secretions persisted. All diamidines tested suppressed the beta-cell function, with a log-dose-response proportionality, the mesylate compound being more potent than pentamidine isethionate, and the lipophilic analogs more than the hydrosoluble diamidines. Electron microscopy revealed distinct morphological alterations in islets exposed to pentamidine, the intensity of these changes being dose-and time-dependent, and the beta cells more severely damaged than the non-beta cells. 51Cr-labelled islet cells and RIN 5 F cells consistently appeared more sensitive to pentamidine cytotoxicity than rat fibroblasts, myeloma cells and hepatocytes. The pentamidine-induced suppression of beta-cell function was not, in conditions tested, affected by the presence of nicotinamide and the hexose concentration in the medium. The kinetics of islet damage were slower than those of streptozotocin and alloxan-induced islet damage. The present study confirms that pentamidine is selectively toxic to islet beta cells, with some features distinct from the alloxan and streptozotocin toxicities to these cells. The mechanism of this process and its precipitating factors in vivo need clarification.
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PMID:Functional and morphological modifications induced in rat islets by pentamidine and other diamidines in vitro. 389 20

In conscious dogs intravenously infused somatostatin (3.3 mug per min for 1 h) caused prompt and sustained declines in mean plasma insulin and glucagon, even during alanine infusion and intraduodenal casein hydrolysate feeding; plasma glucose declined, but not significantly. 6.7 mug per min of somatostatin significantly lowered pancreatoduodenal vein glucagon and insulin within 2.5 min and profoundly suppressed their secretion throughout the infusion. Consistent bihormonal suppression occurred at rates as low as 24 ng per kg per min, but was variable at 12 and 2.4 ng per kg per min. When somatostatin-induced (3.3 mug per min) hypoglucagonemia was corrected by exogenous glucagon, hyperglycemia occurred. In dogs with long-standing insulin-requiring alloxan diabetes 3.3 mug per min of somatostatin suppressed glucagon to 55 pg per ml throughout the 30-min infusion and lowered glucose by 36.4+/-6.1 mg per dl, about 1 mg per dl per min. Glucagon suppression was maintained despite alanine infusion, and glucose, which rose 29 mg per dl during alanine infusion without somatostatin, declined 58 mg per dl in the somatostatin-treated diabetic dogs despite alanine. Continuous infusion of somatostatin for 24 h in five insulin-requiring alloxan-diabetic dogs suppressed glucagon and lowered glucose significantly, usually to below normal. It is concluded that in normal dogs pharmacologic doses of somatostatin virtually abolish insulin and glucagon secretion in the basal state and during hyperaminoacidemia. Hyperglycemia occurs during somatostatin-induced insulin lack only if hypoglucagonemia is corrected. Somatostatin suppresses glucagon in diabetic dogs and lowers their plasma glucose approximately 1 mg per dl per min, even when the gluconeogenic substrate alanine is abundant. Glucagon suppression can be maintained for several hours in such dogs and hyperglycemia is thereby reduced.
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PMID:Somatostatin-induced changes in insulin and glucagon secretion in normal and diabetic dogs. 443 39

While alloxan treatment stimulated insulin secretion, alloxan pretreatment reduced arginine and glucose-induced insulin secretion in the isolated perfused rat pancreas. The transient insulin secretion by alloxan was inhibited by 3-O-methylglucose and somatostatin. Diminished insulin response to arginine and glucose induced by pretreatment with alloxan was restored by the addition of 3-O-methylglucose, whereas the addition of somatostatin did not improve the impaired insulin secretion. These results indicate that alloxan induced insulin secretion is not due to an uncontrolled leakage, but that the stimulatory and inhibitory action of alloxan on insulin secretion might be initiated by the binding of alloxan to the hexose transport site.
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PMID:The dual effect of alloxan modulated by 3-O-methylglucose or somatostatin on insulin secretion in the isolated perfused rat pancreas. 610 26

To investigate the effect of acute elevation of plasma free fatty acids (FFA) on the secretion of splanchnic somatostatin-like immunoreactivity (SLI), the peripheral venous, pancreatic, and gastric venous effluent levels of SLI were measured in normal and chronic alloxan diabetic dogs before and after the infusion of a fat emulsion supplemented with heparin. In normal conscious dogs heparin injected during the infusion of a fat emulsion elevated FFA levels from a mean (+/-SE) base-line level of 0.7+/-0.1 meq/liter to a peak value of 1.5+/-0.1 meq/liter (P < 0.001) and plasma SLI rose from a mean (+/-SE) base-line value of 145+/-7 pg/ml to a peak of 253+/-44 pg/ml (P < 0.05). Neither the infusion of glycerol, of fat emulsion without heparin, of heparin alone nor of saline itself had an effect on either the plasma level of FFA or SLI. In another group of anesthetized dogs with surgically implanted catheters the administration of fat emulsion plus heparin was accompanied by more than a two-fold rise in the concentration of SLI in the venous effluent of the pancreas and of the gastric fundus and antrum in association with an elevation of FFA levels. In a group of conscious diabetic dogs fat emulsion plus heparin raised FFA from a mean base-line level of 1.2+/-0.2 to 1.6+/-0.3 meq/liter (P < 0.05) and SLI rose from a mean base-line level of 185+/-9 pg/ml to a peak value of 310+/-44 pg/ml (P < 0.01). Although SLI levels were significantly greater than in normal dogs at several time points after the rise in FFA, the magnitude of the increment in diabetic dogs did not differ from normal. These results demonstrate that a rise in FFA levels is a potent stimulus for SLI secretion from the pancreas and stomach and raise the possibility that FFA is an important physiological regulator of SLI secretion.
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PMID:Evidence for a role of free fatty acids in the regulation of somatostatin secretion in normal and alloxan diabetic dogs. 610 66

High plasma levels of free fatty acids (FFA) stimulate the secretion of splanchnic somatostatin, and both are elevated in insulin deficiency. To determine if the hypersomatostatinemia of insulin deficiency is secondary to high FFA levels, plasma somatostatin-like immunoreactivity (SLI) was measured in a group of insulin-deprived alloxan-diabetic dogs during nicotinic acid-induced lowering of their elevated plasma FFA to normal, and in a group of nondiabetic dogs during nicotinic acid-induced lowering of their FFA to subnormal values. In insulin-deprived diabetic dogs, nicotinic acid reduced plasma FFA from 1.07 +/- 0.2 (M +/- SE) mmol/L to 0.6 +/- 0.1 mmol/L (P less than 0.02), approximately the basal FFA level in normal dogs. This was accompanied by a significant decline in plasma SLI levels from a mean baseline of 247 +/- 15 pg/ml to a mean nadir of 199 +/- 10 pg/ml (P less than 0.005). The latter was, nevertheless, significantly above the basal SLI level of the nondiabetic dogs. In contrast, in normal dogs, nicotinic acid-induced reduction in FFA from 0.54 +/- 0.02 mmol/L to 0.24 +/- 0.03 mmol/L (P less than 0.001) was associated with only a small and inconsistent decrease in SLI. These findings suggest that the hypersomatostatinemia of insulin-deficient alloxan-diabetic dogs is, in part, secondary to high plasma FFA levels.
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PMID:High plasma free fatty acid levels contribute to the hypersomatostatinemia of insulin deficiency. 611 Jun 3

The secretion of somatostatin and glucagon by the perfused rat pancreatico-duodenal preparation was examined in situ under control conditions and after the induction of acute insulin deficiency by alloxan or streptozotocin. A 10 min 0.625 mmol/l alloxan perfusion resulted in an immediate and transient increase in basal insulin and glucagon release and a slightly delayed and persistent increase in basal somatostatin secretion. The insulin responses to 16.7 mmol/l glucose, 1 mmol/l theophylline, and 19 mmol/l arginine alone or in combination were virtually eliminated by alloxan treatment. Somatostatin secretion in response to the stimuli was completely inhibited or markedly attenuated. The glucagon-suppressive effect of glucose was unaltered by alloxan and the stimulatory effect of arginine was enhanced. Addition of 1 microgram/ml porcine insulin to the perfusion medium did not modify the alterations in somatostatin and glucagon responses to arginine. Streptozotocin treatment 90 min prior to the onset of perfusion resulted in changes in somatostatin, glucagon, and insulin responses to glucose and arginine similar to those of alloxan. The present results are consistent with an effect of alloxan and streptozotocin on the D cell similar to that on the B cells, namely, interference with a glucose-mediated effect on hormone secretion.
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PMID:Acute effects of alloxan- and streptozotocin-induced insulin deficiency on somatostatin and glucagon secretion by the perfused isolated rat pancreatico-duodenal preparation. 611 Jun 4

It has been previously demonstrated that glucagon increased plasma post-heparin lipolytic activity (PHLA) in normal rats, but this was not the case in alloxan diabetic rats. The present work was designed to determine if the administration of exogenous glucagon (0.2 mg i.v.) during suppression of endogenous hormone secretion with somatostatin modifies the plasma post-heparin lipolytic activity in normal rats and the action of such hormone upon monoglyceride hydrolase (MGH) activity. It was found that exogenous glucagon significatively increased PHLA and MGH activity in normal rats after 18-24 hours of starvation. However, both enzymatic activities were not influenced by exogenous glucagon when they were measured during somatostatin administration. Therefore it is believed that the enhancement of these activities observed when somatostatin was not simultaneously given was due to the insulin secretion that follows the glucagon injection.
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PMID:Glucagon action upon plasma post-heparin lipolytic and monoglyceride hydrolase activities. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin. 611 26

Basal and postprandial somatostatin-like immunoreactivity (SLI) is elevated in the peripheral venous plasma of chronic alloxan-diabetic dogs. To determine if this hypersomatostatinemia was the consequence of increased somatostatin release from the pancreas, stomach, or both, plasma SLI was measured in the pancreaticoduodenal, antral, and fundic veins and in the inferior vena cava in response to stimulation by a gastric liver test meal, followed by an intragastric HCl load. Basal and postprandial inferior vena caval plasma SLI levels were significantly higher than the control level (P less than 0.05-0.001), confirming earlier findings. Basal pancreatic venous SLI was 780 +/- 45 pg/ml in the diabetic dogs and 493 +/- 65 pg/ml in the controls (P less than 0.02). In response to the liver meal at pH 7, the incremental pancreatic venous SLI level in the diabetic dogs was 1630 +/- 95 pg/ml, and after HCl it rose to 9479 +/- 384 pg/ml compared to 938 +/- 80 and 4677 +/- 192 pg/ml, respectively, in the controls (P less than 0.02 and P less than 0.005). However, antral and fundic venous SLI levels in the diabetic dogs did not differ from the controls in either basal or stimulated states. The present data demonstrate that the pancreas and not the stomach is the probable source of the peripheral hypersomatostatinemia of alloxan-diabetic dogs.
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PMID:Origin of peripheral venous hypersomatostatinemia in alloxan-diabetic dogs. 611 95


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