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 present study was designed to characterize further the role of insulin in the regulation of glucose utilization during a 2-h exercise at 40% VO2max in 14 h fasted, healthy subjects. Endogenous insulin and glucagon were suppressed by somatostatin infusion and replaced singly or in combination to match the hormonal concentrations observed during similar exercise in saline-treated control subjects. Glucose kinetics were determined by a tracer method using D-[2,3,4,6,6-2H]glucose. In the exercising controls, during the last hour of the exercise, plasma glucose remained stable (4.26 +/- 0.06 mmol/L) and glucose utilization (Rd) increased significantly (p < 0.05) from 12.2 +/- 0.2 to 28.6 +/- 1.3 mumol.kg-1.min-1. During insulin deficiency without glucagon replacement, plasma glucose was maintained at 3.74 +/- 0.10 mmol/L by dextrose infusion, but with glucagon replacement plasma glucose increased to 6.69 +/- 0.24 mmol/L (p < 0.05). These hormonal changes were associated with an increase in Rd to 18.6 +/- 1.1 mumol.kg-1.min-1 (p = ns versus resting controls) and to 37.9 +/- 1.9 mumol.kg-1.min-1 (p < 0.05 versus resting controls), respectively. When insulin was replaced without glucagon replacement, plasma glucose was maintained at 3.85 +/- 0.06 mmol/L by dextrose infusion and Rd increased significantly (p < 0.05) from the resting value to 25.9 +/- 0.7 mumol.kg-1.min-1. When insulin was replaced together with glucagon, the plasma glucose (4.29 +/- 0.15 mmol/L) and the Rd (32.1 +/- 0.9 mumol.kg-1.min-1, p < 0.05 versus the resting value) obtained were similar to the values from the saline exercising control. Glucose metabolic clearance rate (MCR) significantly increased (p < 0.05) during exercise in all protocols. When insulin was made deficient, MCR increased 2-fold (p < 0.05) during exercise (2.7 to 4.8 and 5.4 mL.kg-1.min-1, respectively, with and without glucagon deficiency). However, when insulin was present, with and without glucagon deficiency, it increased further to 6.7 and 7.5 mL.kg-1.min-1, respectively, and values were different (p < 0.05) from glucose MCRs during insulin deficiencies. It is concluded that in 14 h fasted, healthy subjects, exercise per se can stimulate whole body glucose uptake even when insulin is made deficient. Insulin is necessary, however, for optimal glucose utilization during prolonged mild intensity exercise.
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PMID:Glucose metabolism during exercise in man: the role of insulin in the regulation of glucose utilization. 910 Oct 63

Thyrotropin-releasing hormone (TRH) administered intracerebroventricularly and intravenous injection of 2-deoxy-D-glucose (2-DG) stimulate pancreatic exocrine secretion via vagal efferent nerve excitation. We examined whether centrally administered somatostatin would inhibit pancreatic exocrine secretion that was stimulated by vagal efferent nerve excitation in conscious rats. The animals were prepared with cannulas draining bile and pancreatic juice separately and with a duodenal cannula, a cerebroventricular cannula, and a right jugular vein cannula. Intracerebroventricular injection of somatostatin (0.4 or 4 nmol) significantly inhibited pancreatic secretion induced by TRH (50 or 500 pmol) in a dose-dependent manner. Intravenous injection of somatostatin had no effect on pancreatic secretion stimulated by TRH. On the other hand, somatostatin injected centrally did not affect pancreatic secretion induced by 2-DG (75 mg/kg) or basal secretion. These results suggest that TRH and 2-DG stimulate vagal efferent nerves via distinct mechanisms and that central somatostatin selectively inhibits excitation of the vagus induced by peptidergic (TRH) stimulation.
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PMID:Central somatostatin prevents vagal efferent nerve excitation produced by TRH but not by 2-deoxy-D-glucose. 912 60

The aim of this study was to obtain pharmacological evidence for the presence and participation of K+ channels in amphibian pancreatic islets. Pancreases from the toad Bufo arenarum were thus incubated with activators or blockers of K+ channels and the immunoreactive insulin released into the medium was measured by radioimmunoassay. Two K(+)-ATP channel openers (diazoxide and BPDZ44) inhibited; while a K(+)-ATP channel blocker (tolbutamide) and metabolizable sugars (glucose, glyceraldehyde) significantly stimulated the output of insulin. Although a nonmetabolizable sugar (galactose) failed to increase insulin release, dinitrophenol decreased the secretagogue effect of glucose. By contrast, although somatostatin and clonidine blocked the release of insulin, tetraethylammonium significantly stimulated secretion. For each compound tested, the effects on both insulin secretion and B-cell K+ channel activity were similar to those observed in the mammalian pancreas. These findings point to the existence of mammalian-like K+ channels in the B-cells of some amphibians.
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PMID:Effect of activators and inhibitors of K+ channels on insulin secretion in the amphibian pancreas. 922 48

Carcinoid tumors have high numbers of somatostatin receptors that allow scintigraphic imaging with the radiolabeled somatostatin analog octreotide. Experience, however, with PET using 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) in carcinoid is very limited. In two prior studies which investigated the utility of 18FDG-PET in cancer detection, three patients with small, solitary, indolent carcinoid tumors had false-negative results. We report a case where 18FDG-PET imaging was false-negative in a patient with known metastatic carcinoid and a positive octreotide scan.
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PMID:False-negative fluorine-18-FDG PET in metastatic carcinoid. 929 92

NIDDM is associated with excessive rates of endogenous glucose production in both the postabsorptive and postprandial states. To determine whether this is due to an intrinsic increase in hepatic sensitivity to glucagon, 9 NIDDM and 10 nondiabetic subjects were studied on three occasions. On each occasion, glycogen was labeled the evening before the study with subjects ingesting meals containing [6-3H]galactose. Beginning at 6:00 A.M. on the following morning, somatostatin was infused to inhibit endogenous hormone secretion. Insulin concentrations were maintained constant at basal levels (defined as that necessary to keep glucose at approximately 5 mmol/l) in each individual. On one occasion, glucagon was infused at a rate of 0.65 ng x kg(-1) x min(-1) throughout the experiment, resulting in glucagon concentrations of approximately 130 pg/ml and a slow but comparable fall in endogenous glucose production with time in both groups. On the other two occasions, the glucagon infusion was increased at 10:00 A.M. to either 1.5 or 3.0 ng x kg(-1) x min(-1), resulting in an increase in glucagon concentrations to approximately 180 and 310 pg/ml, respectively. The increment in endogenous glucose production (i.e., area above basal) did not differ in diabetic and nondiabetic subjects during either the 1.5 ng x kg(-1) x min(-1) (0.75 +/- 0.055 vs. 0.78 +/- 0.048 mmol/kg) or 3.0 ng x kg(-1) x min(-1) (1.06 +/- 0.066 vs. 1.10 +/- 0.073 mmol/kg) glucagon infusions. In contrast, the amount of [6-3H]glucose released from glycogen was lower (P < 0.05) in the diabetic than nondiabetic subjects during both glucagon infusions. The specific activity of glycogen, calculated as the integrated release of [6-3H]glucose divided by the integrated release of unlabeled glucose, was lower (P < 0.05) in diabetic subjects than in nondiabetic subjects during both the 1.5 ng x kg(-1) x min(-1) (19.0 +/- 3.9 vs. 41.4 +/- 5.7 dpm/micromol) and 3.0 ng x kg(-1) x min(-1) (19.1 +/- 3.1 vs. 36.5 +/- 7.2 dpm/micromol) glucagon infusions, implying that a greater portion of the glucose released from glycogen was derived from the indirect pathway. We concluded that although NIDDM is not associated with an intrinsic alteration in hepatic sensitivity to glucagon, it does alter the relative contributions of the direct and indirect pathways to nocturnal glycogen synthesis.
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PMID:Assessment of hepatic sensitivity to glucagon in NIDDM: use as a tool to estimate the contribution of the indirect pathway to nocturnal glycogen synthesis. 939 88

We recently reported that the nonmetabolizable glucose analogue, 3-O-methylglucose, stimulates somatostatin secretion in the perfused dog pancreas. In this study, we report that 3-O-methylglucose also stimulates insulin secretion in the dog pancreas. The effect was present at 5.5 mM glucose (p < 0.001) but not at O or 2.7 mM glucose. The inhibitor of glucose metabolism, mannoheptulose, blocked the insulinotropic action of 3-O-methylglucose. In contrast, 3-O-methylglucose had no effect on insulin secretion in the perfused rat pancreas. We conclude that 3-O-methylglucose stimulates insulin secretion in the dog and that the effect requires the presence of stimulatory concentrations of D-glucose.
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PMID:Effect of 3-O-methylglucose on insulin secretion in the perfused dog and rat pancreas. 959 13

Dorsal root ganglion neurons innervating skin via the saphenous nerve, muscle via the gastrocnemius nerve and viscera via the splanchnic nerve, were identified by retrograde tracing with Fast Blue applied to the cut nerve. Only neuronal profiles with nuclei were counted. At the survival times used no changes in immunohistochemical labelling patterns were detectable in the axotomized neurons. Percentages of Fast Blue-labelled neuronal profiles that were immunolabelled were calculated. The values for markers of carbohydrate groups were for skin, muscle and viscera, respectively: the lectin peanut agglutinin 55%, 24%, and 50%; the lectin soybean agglutinin 72%, 56%, 61%; the antibody 2C5 (against lactoseries groups) 43%, 20%, 6%; the antibodies SSEA-4 (against globoseries groups) 6%, 12%, 0% and SSEA-3 (against globoseries groups) 6%, 5%, 0%. The values for neurofilament rich profiles were for skin, muscle and viscera, respectively: 34%, 43%, 19%, and for carbonic anhydrase were 10%, 33%, 2%. Values for neuropeptides were, for calcitonin gene-related peptide 51%, 70%, 99%, for substance P 21%, 51%, 82%, and for somatostatin 10%, 2% and 0%. The population of skin afferents therefore contained the highest proportion of profiles expressing galactose containing carbohydrate groups labelled by 2C5 and the lectins and the highest proportion of cells with somatostatin. In contrast they had the lowest proportions of cells with calcitonin gene-related peptide and substance P, compared with the other tissues. Muscle afferents had the highest proportions compared with the other tissues of the neurofilament-rich, carbonic anhydrase-positive and SSEA-4-labelled profiles, but the lowest proportions of profiles with lectin binding. The splanchnic visceral afferents had the highest proportions, compared with the other tissues, of neuronal profiles labelled for calcitonin gene-related peptide and substance P, but the lowest proportions of neurofilament rich profiles and of profiles with carbonic anhydrase or 2C5 labelling and they totally lacked any labelling for globoseries carbohydrates and somatostatin. Both the muscle and skin afferent populations had clear small cell and large cell peaks in their size distributions, with the small cell peak being larger for skin than muscle afferents and the large cell peak being more marked for muscle afferents. The visceral afferent profiles had a unimodal size distribution with the peak size being between the small and large cell peaks of the somatic afferent units. This study therefore shows that the patterns of immunohistochemical labelling and cell size of primary afferent neurons differ according to their peripheral target tissue.
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PMID:Differences in expression of oligosaccharides, neuropeptides, carbonic anhydrase and neurofilament in rat primary afferent neurons retrogradely labelled via skin, muscle or visceral nerves. 960 20

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

We investigated the role of hypothalamic glutamate receptors in mediating the stimulatory effect of low glucose (< 5 mM) on somatostatin release. We also studied whether alteration in glutamate release might contribute to the reduced hypothalamic somatostatin response to low glucose observed in diabetic (Goto-Kakizaki) rat hypothalami. Hypothalamic somatostatin release in response to incubation with 1 mM D-glucose was inhibited by the ionotropic glutamate receptor antagonists MK801, D-AP5 and DNQX but not by the metabotropic antagonists L-AP3 or MCPG. The release of somatostatin was increased by the ionotropic agonists NMDA, AMPA and kainate but not by metabotropic agonists t-ACPD or L-AP4. Basal and peak glutamate release in response to incubation with 1 mM glucose, were significantly lower from GK hypothalami There were no significant differences in the basal or stimulated release of serine and GABA. These data indicate that ionotropic NMDA/AMPA/kainate receptors and not metabotropic receptors mediate the effects of glucose on rat hypothalamic somatostatin release. Reduced hypothalamic somatostatin release in response to low glucose in diabetic (Goto-Kakizaki) rats may well be secondary, at least in part, to reduced glutamate release.
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PMID:Glutamate pathways mediate somatostatin responses to glucose in normal and diabetic rat hypothalamus. 966 52

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


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