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 somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Ceoncentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mM glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H]cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H]cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H]cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30%. It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase.
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PMID:Studies on the mechanisms of somatostatin action on insulin release. IV. effect of somatostatin on cyclic AMP levels and phosphodiesterase activity in isolated rat pancreatic islets. 19 42

Glucose-induced insulin secretion is enhanced by a preceeding glucose stimulus. The characteristics of this action of glucose were investigated in perfused pancreas and collagenase-isolated islets of Langerhans. A 20- to 30-min pulse of 27.7 mM glucose enhanced both the first and second phase of insulin release in response to a second glucose stimulus by 76-201%. This enhancement was apparent as an augmented maximal insulin release response to glucose. The effect of priming with glucose was seen irrespective of whether the pancreatic tissue was obtained from fed or fasted rats. Separating the two pulses of hexose by a 60-min time interval of exposure to 3.3 mM glucose did not abolish the potentiation of the second pulse. Omission of Ca(++) as well as the inclusion of somatostatin or mannoheptulose during the first pulse abolished insulin secretion during this time period; however, only the inclusion of mannoheptulose deleted the potentiation of the second pulse. d-Glyceraldehyde, but not pyruvate, d-galactose, or 3-isobutyl-1-methylxanthine, could substitute for glucose in inducing potentiation. In islets labeled with [2-(3)H]adenine, the [(3)H]cyclic AMP response to glucose was increased by 35% when measured after 1 min, but was increased only marginally after 2-10 min of stimulation with a second pulse of glucose. The production of (3)H(2)O from glucose was not affected by glucose priming. It is concluded that (a) the induction of the glucose-induced, time-dependent potentiation described here is dependent on glucose metabolism but not on stimulation of cyclic AMP, calcium fluxes, or insulin release per se; (b) the mechanisms that mediate the pancreatic "memory" for glucose are unknown but do not seem to involve to a major extent an increased activity of the adenylate cyclase-cyclic AMP system of the beta-cell; (c) the evidence presented supports the hypothesis of a dual role of glucose for insulin release.
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PMID:Immediate and time-dependent effects of glucose on insulin release from rat pancreatic tissue. Evidence for different mechanisms of action. 20 21

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

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

Arterial (A) and renal venous (RV) concentrations and net splanchnic exchange of glucose, fructose, lactate, pyruvate, glycerol, and alanine were studied in the basal state and during a 135-min intravenous infusion of fructose at 2 mmol/min in healthy subjects after a 60-h fast. After 45 min of the fructose infusion, somatostatin (9 microgram/min) was infused for 60 min to induce hypoglucagonemia. Fructose infusion resulted in a net uptake of this hexose by the kidney as well as the splanchnic bed. Estimated renal uptake of fructose could account for the disposal of 20% of the administered fructose load while splanchnic uptake accounted for 38%. The fructose infusion resulted in a rise in blood glucose of 0.9 mmol/L, a 35% increase in net glucose output from the splanchnic bed, and a consistent net output of glucose from the kidney (A-RV = -0.17 +/- 0.05 mmol/L as compared with 0 +/- 0.03 in the basal state, P less than 0.02). Net glucose release from the kidney could account for 55% of the net renal uptake of fructose. The fructose infusion also resulted in a marked change in renal lactate balance from a net uptake in the basal state (A - RV = 0.05 +/- 0.01 mmol/L) to a net output during fructose administration (A - RV = -0.10 +/- 0.04). Administration of somatostatin resulted in a fall in arterial glucagon levels and a 35% decrease in splanchnic glucose output but failed to alter the arterial-renal venous difference for glucose observed during the fructose infusion. We conclude that in 60-h fasted man: (a) intravenous infusion of fructose results in a net uptake of this hexose by the kidney as well as the liver, (b) this uptake is accompanied by stimulation of renal as well as hepatic glucose production and renal production of lactate, and (c) hypoglucagonemia inhibits splanchnic but not renal glucose output during fructose infusion. These data indicate that the kidney is an important site of fructose disposal and that glucose and lactate are end products of renal fructose metabolism.
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PMID:Role of the kidney in the metabolism of fructose in 60-hour fasted humans. 613 22

Glucose exerts opposite effects upon glucagon and insulin release from the endocrine pancreas. Glucose uptake and oxidation were therefore compared in purified A- and B-cells. In purified B-cells, the intracellular concentration of glucose or 3-O-methyl-D-glucose equilibrates within 2 min with the extracellular levels, and, like in intact islets, the rate of glucose oxidation displays a sigmoidal dose-response curve for glucose. In contrast, even after 5 min of incubation, the apparent distribution space of D-glucose or 3-O-methyl-D-glucose in A-cells remains much lower than the intracellular volume. In A-cells, both the rate of 3-O-methyl-D-glucose uptake and glucose oxidation proceed proportional to the hexose concentration up to 10 mM and reach saturation at higher concentrations. Addition of insulin failed to affect 3-O-methyl-D-glucose or D-glucose uptake and glucose oxidation by purified A-cells. Glucose releases 30-fold more insulin from islets than from single B-cells, but this marked difference is not associated with differences in glucose handling. The rate of glucose oxidation is virtually identical in single and reaggregated B-cells and is not altered after addition of glucagon or somatostatin. It is concluded that the dependency of glucose-induced insulin release upon the functional coordination between islet cells is not mediated through changes in glucose metabolism.
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PMID:Differences in glucose handling by pancreatic A- and B-cells. 614 Nov 62

Several meglitinide analogs are currently under investigation as potential insulinotropic tools for the treatment of noninsulin-dependent diabetes. The present study aimed to further insight into the effect of these agents on the secretion of insulin, glucagon, and somatostatin by the isolated perfused pancreas. Both repaglinide (0.01 microM) and A-4166 (1.0 microM) stimulated insulin and somatostatin release, but failed to affect glucagon output, from pancreases exposed to 5.6 mM D-glucose. The secretory response of the B- and D-cells to the hypoglycemic agents was much less marked than that caused by a rise in hexose concentration from 5.6-16.7 mM. Although repaglinide was tested at a concentration a hundred times lower than that of A-4166, the drug-induced increase in both insulin and somatostatin secretion persisted for a longer time after exposure to repaglinide, than to A-4166. The relevance of these findings to the use of meglitinide analogs as antidiabetic agents is double. First, they document that these drugs, although enhancing both insulin and somatostatin release, do not provoke an undesirable stimulation of glucagon secretion. Second, they indicate that even at a very low concentration, repaglinide provokes a protracted insulinotropic action, thus suggesting that the reversibility of the secretory response to this or other meglitinide analogs represents an intrinsic molecular attribute, unrelated to either their biological potency or the relative extent of B-cell stimulation.
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PMID:Stimulation of insulin and somatostatin release by two meglitinide analogs. 965 67

In isolated perfused pancreas from normal rats, a rise in d-glucose concentration from 3.3 to 8.3 mM provoked a rapid phasic stimulation of both insulin and somatostatin secretion and rapid fall in glucagon output, these changes being reversed when the concentration of the hexose was brought back to its initial low level. In the presence of 8.3 mM d-glucose, the administration of either human or mouse leptin (10 nM in both cases) for 15 min failed to affect significantly the perfusion pressure and release of the three hormones. It is concluded that leptin does not exert any major immediate and direct effect upon pancreatic insulin, glucagon and somatostatin secretion, at least at the physiological concentration of d-glucose normally found in the plasma of fed rats.
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PMID:Failure of human and mouse leptin to affect insulin, glucagon and somatostatin secretion by the perfused rat pancreas at physiological glucose concentration. 972 92

Isolated perfused rat pancreases were exposed, in the presence of 10. 0 mM L-leucine, to either alpha-D-glucose pentaacetate, beta-L-glucose pentaacetate, or unesterified D-glucose, all tested at a 1.7 mM concentration. The pentaacetate ester of alpha-D-glucose and, to a lesser extent, that of beta-L-glucose stimulated both insulin and somatostatin release, whereas unesterified D-glucose failed to do so. In the case of insulin output, the two esters differed from one another not solely by the magnitude of the secretory response but also by its time course and reversibility. Compared with these data, the most salient difference found in the case of somatostatin release consisted of the absence of an early secretory peak in response to alpha-D-glucose pentaacetate administration and the higher paired ratio between the secretory responses evoked by the esters of glucose and by unesterified D-glucose (5.5 mM) administered at the end of the experiments. The two esters provoked an initial and short-lived stimulation of glucagon secretion, in sharp contrast to the immediate inhibitory action of unesterified D-glucose. Thereafter, alpha-D-glucose pentaacetate, but not beta-L-glucose pentaacetate, caused inhibition of glucagon release, such an effect being reversed when the administration of the ester was halted. These findings indicate a dual mode of action of glucose pentaacetate esters on hormonal secretion from the endocrine pancreas. The intracellular hydrolysis of alpha-D-glucose pentaacetate and subsequent catabolism of its hexose moiety may contribute to the early peak-shaped insulin response to this ester, to the persistence of a positive secretory effect in B and D cells after cessation of its administration, and to the late inhibition of glucagon release. However, a direct effect of the esters themselves, by some as-of-yet unidentified coupling process, is postulated to account for the stimulation of insulin and somatostatin release by beta-L-glucose pentaacetate and for the initial enhancement of glucagon secretion provoked by both glucose esters.
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PMID:Dual mode of action of glucose pentaacetates on hormonal secretion from the isolated perfused rat pancreas. 975 79

The effects of alpha- and beta-2-deoxy-D-glucose tetraacetate (1.7 and 8.5 mM) on insulin, somatostatin, and glucagon secretion from isolated rat pancreases perfused in the presence of 8.3 mM D-glucose were compared with those of unesterified 2-deoxy-D-glucose tested at the same two concentrations. The unesterified glucose analog caused, in a concentration-related manner, inhibition of glucose-induced insulin and somatostatin release and augmentation of glucagon secretion. The two anomers of 2-deoxy-D-glucose tetraacetate, however, increased the secretion rate of all three hormones; this effect was also related to the concentration of the esters. No obvious anomeric specificity of the secretory response to 2-deoxy-D-glucose tetraacetate was observed. These findings indicate that the insulinotropic action of hexose esters cannot be accounted for solely by the metabolic effect of their glucidic moieties. They suggest that the A, B, and D cells of the endocrine pancreas are each equipped with a receptor system responsible for the direct recognition of monosaccharide esters as secretagogues. They further support the view that a paracrine effect of insulin on glucagon-producing cells does not represent a major component in the regulation of their secretory activity.
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PMID:Stimulation by 2-deoxy-D-glucose tetraacetates of hormonal secretion from the perfused rat pancreas. 1019 5


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