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)

A modified insulin suppression test was adopted to assess the diurnal variation in insulin sensitivity and insulin clearance in 14 non-insulin-dependent diabetes mellitus (NIDDM) patients and eight age-, sex- and weight-matched normal subjects. The modified insulin suppression test was combined with an infusion of regular insulin, 30 mU/min x m2; glucose, 6 mg/kg x min; and somatostatin, 500 micrograms/h, for 120 minutes followed by only a somatostatin infusion for 60 minutes. Blood samplings were performed at appropriate times to obtain data on steady-state plasma insulin (SSPI), steady-state plasma glucose (SSPG as an index of insulin sensitivity), metabolic clearance and the half disappearance time (T1/2) of insulin. Blood specimens were also obtained during SSPI for measurement of erythrocyte insulin receptor binding. Each subject took the insulin suppression test twice. One test was started at 8 am and the other at 4 pm; each test was preceded by 16 hours of fasting. The order of the insulin suppression tests in each subject was randomized and balanced. In normal subjects, the SSPG level was lower in the morning than in the afternoon (118.0 +/- 43.6 vs 150.3 +/- 34.2 mg/dL, p less than 0.05). The NIDDM patients had a higher SSPG in the morning (217.7 +/- 51.4 vs 188.3 +/- 40.6 mg/dL, p less than 0.01). There was no diurnal difference in insulin clearance or the T1/2 in either normal subjects or NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diurnal variation of insulin sensitivity in NIDDM patients and normal subjects. 135 86

Exogenous epidermal growth factor (or somatostatin) can stimulate (or inhibit) proliferation of pancreatic cancer cells, with a corresponding decrease (or increase) of the saturation index of the cell membrane and up-regulation (or down-regulation) of insulin receptor expression. By measuring the saturation index and insulin receptor numbers on the cell membrane it may be possible to evaluate the curative effects of treatment on pancreatic cancer at an early time.
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PMID:[Correlation of proliferation of pancreatic cancer cells with both saturation index and cell membrane insulin receptors]. 136 99

Insulin receptor function, glycogen synthase activity, and activation by phosphatases were studied in biopsies of human skeletal muscle under conditions of hyperglycemia and/or hyperinsulinemia for 150 minutes. Twenty-one healthy volunteers underwent either (A) a hyperinsulinemic, euglycemic clamp (serum insulin, 160.0 +/- 7.7 mU/L; plasma glucose, 4.9 +/- 0.1 mmol/L; n = 9), (B) a hyperglycemic clamp during normoinsulinemia (serum insulin, 18.1 +/- 3.3 mU/L; plasma glucose, 12.9 +/- 0.2 mmol/L; n = 6), or (C) a combined hyperinsulinemic, hyperglycemic clamp (serum insulin, 158.3 +/- 15.0 mU/L; plasma glucose, 11.4 +/- 0.8 mmol/L; n = 6). During all studies, the endogenous insulin secretion was inhibited with somatostatin. Insulin binding and kinase activity of insulin receptors solubilized from vastus lateralis muscle biopsies were unaffected by hyperglycemia and/or hyperinsulinemia. Hyperinsulinemia activated the muscle glycogen synthase with a decrease in the half-maximal activation constant (A0.5) for glucose-6-phosphate (G6P) from 0.53 +/- 0.04 to 0.21 +/- 0.02 mmol/L (study A, P less than .02) and from 0.53 +/- 0.06 to 0.19 +/- 0.05 mmol/L (study C, P less than .03). In addition, the rate of glycogen synthase activation by phosphatases increased from 0.078 +/- 0.017 to 0.134 +/- 0.029 U/min/mg protein (study A, P less than .03) and from 0.082 +/- 0.013 to 0.145 +/- 0.033 U/min/mg protein (study C, P = .05). Hyperglycemia during normoinsulinemia did not affect A0.5 or phosphatase activity. In conclusion, (1) hyperinsulinemia for 2 1/2 hours increases glycogen synthase activity and activation by phosphatases independently on the glycemia; and (2) insulin receptor binding and basal and insulin-stimulated receptor kinase activity are not modified during short-term hyperinsulinemia and/or hyperglycemia.
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PMID:Effects of hyperinsulinemia and hyperglycemia on insulin receptor function and glycogen synthase activation in skeletal muscle of normal man. 190 47

Chronic uremia is frequently associated with an impaired carbohydrate tolerance. During the past decade considerable progress have been made in characterizing and quantifying this biochemical abnormality in end-stage renal failure (ESRF). Primarily, this has been possible by means of the glucose clamp technique which basically makes it possible to evaluate insulin sensitivity and glucose-stimulated insulin secretion. Combined with the use of tracer dilution technique, hepatic vein catheterization technique, infusion of somatostatin, forearm or leg techniques and indirect calorimetry, insight into several other major parameters of glucose kinetics has been achieved; i.e. insulin-mediated glucose uptake (IMGU), glucose-induced glucose uptake (GIGU), hepatic glucose production (HGP) splanchnic glucose uptake and oxidative and nonoxidative glucose disposal. Of course, these extra facets make the clamp procedure less feasible to accomplish for technical reasons and demand an extensive knowledge of the limitations of these methods. One major factor behind the reduced glucose tolerance in uremia is an impaired sensitivity to insulin (insulin resistance) in peripheral tissues, mainly in skeletal muscle. In non-dialysed uremic patients the insulin dose-response curve is characterized by a decreased maximal response and by a rightward shift. In general, the insulin resistance is pronounced, but a few weeks on maintenance hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) are enough to improve insulin action significantly. Occasionally, IMGU has been found normal in patients on long-term HD. In contrast to insulin-stimulated glucose uptake, basal glucose turnover is normal in patients with ESRF. The ability of glucose to enhance its own uptake is difficult to measure in human studies, because even small amounts of insulin is able to modulate GIGU profoundly. At basal insulinemia, however, GIGU is markedly impaired in uremia. Recently, it has been suggested that the uremic insulin resistance is located not only in peripheral tissues but also in the liver. At low insulin concentrations, the restraining potency of insulin on HGP seems to be decreased in uremia. Splanchnic glucose uptake is hardly affected, but is always very insensitive to insulin. The glucoregulatory function of the liver is further disturbed in uremia. Acute glucagon exposure elicits an inadequate glucose release, suggesting a coexisting resistance to glucagon. In vitro studies have shown, that the first step in the cascade of reactions initiated by insulin, namely binding to its specific receptor is normal in uremia. In addition, the activity of key enzymes such as the insulin receptor kinase and glycogen synthase have been found within normal in the uremic muscle.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glucose metabolism in non-diabetic and insulin-dependent diabetic subjects with end-stage renal failure. 202 51

Previous studies have suggested that insulin may play a role in the hormonal regulation of neurotransmitter metabolisms within the central nervous system. In order to provide additional information to support this hypothesis, we examined the distribution of insulin receptors within the forebrain of adult male rats. Insulin receptors were localized by immunocytochemistry, using an antibody directed against the carboxy-terminus of the beta-subunit of the insulin receptor. The antibody specificity was tested by immunoprecipitation of brain insulin receptors with antiserum and the purity of the receptor-antibody preparation was determined using hormone binding-assays with radiolabeled insulin and insulin-like growth factor-l. Insulin receptor-like immunoreactivity was found in a widespread, but selective, distribution on neurons throughout the rat forebrain. Double-labeling with glial fibrillary acidic protein did not demonstrate any detectable insulin receptor-like immunoreactivity on glial cells. Areas with the highest density of insulin receptor-like immunoreactivity were found in the olfactory bulbs, hypothalamus and median eminence, medial habenula, subthalamic nucleus, subfornical organ, CA 1/2 pyramidal cell layer of the hippocampus and piriform cortex. Double-staining of hypothalamic sections with somatostatin and vasopressin antisera revealed insulin receptor-like immunoreactivity on a subpopulation of somatostatin neurons in the periventricular region and on vasopressin neurons in the supraoptic nucleus. A moderately dense insulin receptor-like immunoreactivity was observed in layers II-IV of cerebral cortex, medial amygdala, reticular thalamic nucleus, zona incerta, and preoptic and septal regions, whereas a low density of insulin receptor-like immunoreactive neurons was found in basolateral amygdala and most thalamic regions. The basal ganglia and most parts of the thalamus were almost devoid of insulin receptor-like immunoreactivity. Our findings provide morphological support for a direct action of insulin on selected regions of the rat forebrain and suggest that the insulin receptor may modulate synaptic transmission or the release of neurotransmitters and peptide hormones in the CNS.
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PMID:Distribution of insulin receptor-like immunoreactivity in the rat forebrain. 277 Oct 55

This study deals with the influence insulin exerts upon pancreatic somatostatin release. In different incubation systems, isolated rat islets were subjected to addition of either exogenous rat insulin or of anti-insulin serum (AIS). No change in somatostatin release was caused by insulin (25 U/l) during perifusion of freshly isolated islets at 8.3 mmol/l glucose, whereas AIS showed an inhibitory effect. During a 42 hr culture period, somatostatin content of culture medium remained low in the presence of insulin but was elevated when AIS has been added. Therefore, further experiments were carried out after a 2-day period of precultivation. Precultivated islets responded to exogenous insulin with a decrease in somatostatin release in static incubations and in perifusion experiments. It is suggested that the lack of insulin effect in freshly isolated islets is due to alterations in receptors which are restored during islet culture. The inhibition of somatostatin release from freshly isolated islets observed during perifusion with AIS may be caused by anti-insulin receptor antibodies probably present in the anti-insulin serum.
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PMID:Somatostatin release from freshly isolated and cultured rat islets in response to rat insulin and to anti-insulin serum. 286 47

This aim of this study was to determine whether RBC insulin receptor assay represents a clinically useful way of assessing insulin sensitivity in obese children. Steady state plasma glucose (SSPG) was established by a constant infusion of glucose (6 mg/kg/min), insulin (0.8 mU/kg/min) and somatostatin (125 micrograms/m2/h), following the loading dose of somatostatin (125 micrograms/m2). Insulin binding to RBCs was measured by a modified method of Gambhir and was compared with SSPG. Of 21 children with various relative body weight, 8 hyperinsulinemic obese children had a decreased insulin binding to RBCs due to decreased receptor concentrations. The insulin binding was inversely correlated with the fasting serum insulin level and with the insulin area under the O-GTT insulin response curve. In 11 children with various relative body weight, a highly significant inverse relationship was found between SSPG and insulin binding. SSPG was also correlated with the fasting serum insulin level. It was concluded that RBC insulin receptor may quantitatively reflect insulin resistance in obese children, and may be a useful tool for clinical evaluation of tissue insulin sensitivity in children.
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PMID:In vivo insulin sensitivity and insulin binding to erythrocytes in children: insulin resistance in obese children. 613 45

Skeletal muscle sensitivity and responsiveness to insulin and their relationship to overall glucose disposal and insulin binding were determined in 89 premenopausal women of varying body fat topography (waist/hips girth ratio [WHR] 0.64-1.02) and obesity level (percentage of ideal body weight 92-230). As a marker of insulin action, the percentage of total glycogen synthase present in the I form (glucose-6-phosphate independent) was measured in quadriceps muscle biopsies. The increase in percentage of synthase I 1 h after oral glucose loading was not significantly different between nonobese and obese weight-matched subgroups of increasing WHR, but this response was maintained at the expense of increasing plasma insulin levels as the WHR rose. The increase in percentage of synthase I in response to submaximal steady state plasma insulin (SSPI) of approximately 100 microU/ml achieved by the infusion of somatostatin, insulin, and glucose, however, was significantly lower in obese than in nonobese subjects, and was inversely correlated with WHR. The increase in percentage of synthase I correlated inversely with the steady state plasma glucose (SSPG) concentration, which is an index of the efficiency of overall glucose disposal, and directly with insulin binding to circulating monocytes. Insulin binding also correlated inversely with WHR and with fasting plasma insulin levels. When obese subjects were separated into three weight-matched subgroups on the basis of increasing WHR, significant trends to decreased percentage of synthase I response, increased SSPG, and decreased insulin binding were found. In women with predominantly upper body obesity (WHR greater than 0.85), the increase in percentage of synthase in response to submaximal SSPI was diminished, but there was no impairment of percentage of synthase I responsiveness to supramaximal SSPI of approximately 1,000 microU/ml. At supramaximal SSPI levels, SSPG in four obese women was normal, whereas in five women, SSPG concentrations were markedly increased. Our results suggest that in premenopausal women, impaired skeletal muscle insulin sensitivity that results in decreased glucose storage capacity may contribute to the diminished efficiency of glucose disposal and insulin resistance that are associated with upper body obesity. The impairment in skeletal muscle sensitivity may be overcome in vivo at the expense of increasing plasma insulin levels, with maximal responsiveness remaining unimpaired. This defect may result from a reduction in insulin receptor number which could, in turn, be secondary to persistently elevated fasting plasma insulin levels. In some upper body segment obese women, however, an additional defect affecting other insulin-sensitive pathways may also be present.
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PMID:Relationship between skeletal muscle insulin resistance, insulin-mediated glucose disposal, and insulin binding. Effects of obesity and body fat topography. 614 58

A possible role for insulin in stimulating islet beta-cell replication was examined in neonatal rat pancreatic monolayer cultures. Addition of insulin to serum-free medium increased the mitotic index and stimulated dose-dependent increases in [3H]-thymidine incorporation in nuclei of islet beta-cells in aldehyde-thionine-stained autoradiographs. The effects of insulin were not associated with any significant changes in glucagon or somatostatin levels in the culture media. Multiplication stimulating activity (MSA), an insulin-like growth factor, was about 100-fold more potent than insulin: 3 ng/ml MSA stimulated a half-maximal increase in thymidine labeling of beta-cell (+63%, P less than 0.005), whereas 300 ng/ml insulin was required for a similar effect. The maximal effects of insulin and MSA were similar, and the combination of maximal stimulatory concentrations of MSA (30 ng/ml) and insulin (3000 ng/ml) was not more effective than either substance added alone, suggesting that both peptides act on the same mechanism(s) regulating beta-cell replication. Furthermore, an antibody to the insulin receptor did not prevent the stimulatory effects of either insulin or MSA on thymidine labeling of beta-cells. These results demonstrate that insulin can stimulate islet beta-cell replication directly, possibly through a receptor for MSA or another insulin-like growth factor.
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PMID:Insulin and multiplication stimulating activity (an insulin-like growth factor) stimulate islet (beta-cell replication in neonatal rat pancreatic monolayer cultures. 675 33

GLUT4 translocation and activation of glucose uptake in skeletal muscle can be induced by both physiological (i.e., insulin, nerve stimulation, or exercise) and pharmacological (i.e., phorbol ester) means. Recently, we demonstrated that high glucose levels may mimic the effects of phorbol esters on protein kinase C (PKC) and insulin receptor function (J Biol Chem 269:3381-3386, 1994). In this study, we tested whether the previously described effects of phorbol esters on translocation of GLUT4 in myotubes in culture and also in rat skeletal muscle might be mimicked by glucose. We found that stimulation of C2C12 myotubes with both insulin (10(-7) mol/l, 5 min) and glucose (25 mmol/l, 10 min) induces a comparable increase of the GLUT4 content in the plasma membrane. To test whether this effect occurs in intact rat skeletal muscle as well, two different model systems were used. As an in vitro model, isolated rat hindlimbs were perfused for 80 min with medium containing 6 mmol/l glucose +/- insulin (1.6 x 10(-9) mmol/l, 40 min) or 25 mmol/l glucose. As an in vivo model, acute hyperglycemia (> 11 mmol/l glucose, 20 min) was induced in Wistar rats by intraperitoneal injection of glucose under simultaneous suppression of the endogenous insulin release by injection of somatostatin. In both models, subcellular fractions were prepared from hindlimb skeletal muscle, and plasma membranes were characterized by the enrichment of the marker enzyme alpha 1 Na(+)-K(+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute hyperglycemia provides an insulin-independent inducer for GLUT4 translocation in C2C12 myotubes and rat skeletal muscle. 778 29


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