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)

Insulin is produced and secreted by the B cells in the endocrine pancreas. In vivo, insulin secretion is under the control of a number of metabolic, neural and hormonal substances. It is now clear that stimulation of insulin release by fuel secretagogues, such as glucose, involves the closure of K+ channels that are sensitive to the intracellular ATP concentration (KATP channels). This leads to membrane depolarization and the generation of Ca2(+)-dependent action potentials. The mechanisms whereby hormones and neurotransmitters such as adrenaline, galanin and somatostatin, which are released by intraislet nerve endings and the pancreatic D cells, produce inhibition of insulin secretion are not clear. Here we show that adrenaline suppresses B-cell electrical activity (and thus insulin secretion) by a G protein-dependent mechanism, which culminates in the activation of a sulphonylurea-insensitive low-conductance K+ channel distinct from the KATP channel.
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PMID:Activation by adrenaline of a low-conductance G protein-dependent K+ channel in mouse pancreatic B cells. 189 74

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

The role of extrarenal potassium homeostasis is well recognized as a major mechanism for the acute defense against the development of hyperkalemia. The purpose of this report is to examine whether or not the various mechanisms of extrarenal potassium regulation are intact in patients with end-stage renal disease (ESRD). The available data suggest that with the development of ESRD and the uremic syndrome there is impaired extrarenal potassium metabolism that is related to a defect in the Na,K-adenosine triphosphatase (ATPase). The responsiveness of uremic patients to the various effector systems that regulate extrarenal potassium handling is discussed. Insulin is well positioned to play an important role in the regulation of plasma potassium concentration in patients with impaired renal function. The role of basal insulin may be even more important than previously appreciated, since somatostatin infusion causes a much greater increase in the fasting plasma potassium in rats with renal failure than in controls. Furthermore, stimulation of endogenous insulin by oral glucose results in a greater intracellular translocation of potassium in uremic rats than in controls. Under at least two common physiologic circumstances, feeding and vigorous exercise, endogenous catecholamines might also act to defend against acute increments in extracellular potassium concentration. However, it is important to appreciate that the response to beta 2-adrenoreceptor-mediated internal potassium disposal is heterogeneous as judged by the variable responses to epinephrine infusion. Based on the evidence presented in this report, a regimen for the treatment of life-threatening hyperkalemia is outlined. Interpretation of the available data demonstrate that bicarbonate should not be relied on as the sole initial treatment for severe hyperkalemia, since the magnitude of the effect of bicarbonate on potassium is variable and may be delayed. The initial treatment for life-threatening hyperkalemia should always include insulin plus glucose, as the hypokalemic response to insulin is both prompt and predictable. Combined treatment with beta 2-agonists and insulin is also effective and may help prevent insulin-induced hypoglycemia.
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PMID:Extrarenal potassium tolerance in chronic renal failure: implications for the treatment of acute hyperkalemia. 156 35

This study examines the effects of a relatively selective alpha 2-adrenoceptor antagonist, 8-(L-piperazinyl)imado-[1,2-alpha] pyrazine (compound A), and the preferential alpha 2-agonist clonidine on blood glucose, glucose tolerance, and plasma insulin levels in the C57BL/6J ob/ob mouse and its lean littermate. While clonidine raised blood glucose levels and impaired glucose tolerance, oral administration of compound A resulted in decreased blood glucose levels, as well as improved glucose tolerance in ob/ob mice. Insulin levels in ob/ob mice treated with clonidine were significantly reduced, while compound A raised insulin levels threefold and blocked the effects of clonidine when co-administered to the same animals. Clonidine-induced hyperglycemia in lean littermates was not accompanied by a decrease in insulin levels, while a small but significant increase in insulin levels was observed by compound A administration. Glycogen synthesis in diaphragm of ob/ob mice was enhanced after oral administration of compound A and was accompanied by an increase in plasma insulin levels. Concomitant treatment with a potent somatostatin analog to inhibit insulin release blocked the effects of the alpha 2-adrenoceptor antagonist, compound A. These observations suggest that the alpha 2-antagonist studied, increased plasma insulin levels with an accompanying reduction in blood glucose and an improvement in glucose tolerance in a genetic model of insulin resistance. Differential sensitivity to alpha 2-agonist in these genetically obese mice, ob/ob, was demonstrated by decreased insulin levels due to clonidine administration.
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PMID:Effects of an alpha 2-adrenoceptor antagonist on glucose tolerance in the genetically obese mouse (C57BL/6J ob/ob). 197 Aug 47

Syrian golden hamsters bearing N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas were treated for 2 months with the delayed delivery systems of the agonist D-Trp-6-LH-RH (microcapsules releasing 25 micrograms/day for 30 days), the somatostatin analog RC-160 (the microcapsules liberating 48.2 micrograms/day for 30 days), or with the combination of these two analogues. The increase in the dose of RC-160 was possible in view of the lack of toxicity of this analog. This higher dose of RC-160 exerted a greater suppressive effect on pancreatic cancers than the regimens previously used (5-25 micrograms/day). RC-160, D-Trp-6-LH-RH, and their combination reduced the number of pancreatic carcinomas and significantly inhibited tumor growth as compared with the controls. The combination had the strongest tumor-inhibitory effect and reduced tumor weight by 85% as compared with controls. Both the light and electron microscopic analysis of the tumors showed that the inhibitory effect was due to the enhancement of apoptosis (programmed cell death) of tumor cells. Insulin-like growth factor (IGF-I) receptors were detected immunohistochemically in the untreated tumors and their number decreased after the treatment with the analogues. Binding of D-Trp-6-LH-RH and RC-160 to tumor cells was shown immunohistochemically and receptors to these analogues and IGF-I were also determined biochemically by radioligand titration. Treatment with D-Trp-6-LH-RH and RC-160 decreased the binding capacity of receptors for D-Trp-6-LH-RH and IGF-I, producing down-regulation of these receptors. This suggests that pancreatic tumor cells with receptors to these peptides are sensitive to the treatment. This work reinforces the view that the combination of high doses of somatostatin analog RC-160 with LH-RH agonists or antagonists should be considered for the development of a new hormonal therapy for ductal pancreatic cancers.
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PMID:Inhibitory effects of analogs of luteinizing hormone-releasing hormone and somatostatin on pancreatic cancers in hamsters. Events that accompany tumor regression. 197 71

The guinea pig is unusual in that its postnatal growth appears to be independent of GH even though its pituitary gland produces a GH molecule. The effects of fasting on the GH secretory pattern and the GH responses to insulin, GH-releasing factor (GRF), and somatostatin (SS) during fasting have now been studied by automatic microsampling of blood in chronically cannulated normal guinea pigs. Withdrawal of food in both male and female guinea pigs changed the GH secretory pattern dramatically. The normal episodic GH secretory pattern [large GH peaks occurring at 3.6 +/- 0.4-h intervals over a low (approximately 0.5-1.5 ng/ml) baseline secretion] was altered to a pattern of more continuous GH output, characterized by a 10-fold elevated baseline secretion (5-15 ng/ml) with no large secretory episodes or troughs. Glucose injections (three injections of 600 mg, iv, at hourly intervals) in fasted guinea pigs lowered their elevated blood GH levels significantly (from 9.1 +/- 1.1 to 6.5 +/- 0.9 ng/ml). Insulin injections (1, 2, or 6 U, iv) inhibited spontaneous GH pulses in normally fed animals, but had little effect on the high continuous GH tone during fasting. The elevated GH secretion in fasted animals could be inhibited by continuous infusion of SS or a single iv injection of a long-acting SS analog. The secretion of GH during fasting could be further increased, either by injections of GRF (two injections of 2 micrograms, iv, 90 min apart), producing peak levels of 102 +/- 16 and 68 +/- 21 ng/ml (above a baseline output of 8.8 +/- 2.2 ng/ml), or by a continuous iv infusion of GRF (12 micrograms/h). Because the GH secretory pattern in the guinea pig is so sensitive to nutrition and insulin, this species may provide an interesting model in which to study selectively the metabolic, as opposed to growth-promoting, actions and regulation of GH.
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PMID:Effect of food withdrawal and insulin on growth hormone secretion in the guinea pig. 197 50

The release of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) by isolated mouse pancreatic islets was determined during 30-min incubations at 5.6 and 16.7 mmol glucose/l in the absence and presence of gastric inhibitory polypeptide (GIP), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) at concentrations of 1-1000 nmol/l. Insulin release was enhanced (greater than 50%) by GIP (100-1000 nmol/l) and VIP (1 mumol/l) at 5.6 mmol glucose/l, but not at 16.7 mmol glucose/l. Glucagon release was increased by GIP (100-1000 nmol/l), and by VIP and PHI (1-1000 nmol/l) at both glucose concentrations in a dose-related manner (maximum increases greater than tenfold). Somatostatin release was similarly increased by GIP (10-1000 nmol/l) at both glucose concentrations. Only the highest concentration (1 mumol/l) of PHI tested increased somatostatin release (twofold) at 5.6 mmol glucose/l, whereas PHI and VIP (1-1000 nmol/l) reduced (greater than 37%) somatostatin release at 16.7 mmol glucose/l. PP release was increased (49-58%) by 100-1000 nmol GIP/l, but was not significantly altered by VIP, and was reduced (39-56%) by PHI. The results indicate that GIP, VIP and PHI each stimulate glucagon release in a dose-related manner, but they exert discretely different effects on other islet hormones depending upon the dose and the prevailing glucose concentration.
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PMID:Effects of gastric inhibitory polypeptide, vasoactive intestinal polypeptide and peptide histidine isoleucine on the secretion of hormones by isolated mouse pancreatic islets. 197 1

Free fatty acids are known to inhibit carbohydrate disposal and oxidation. This action may play an important role in the pathophysiology of insulin resistance and non-insulin-dependent diabetes mellitus. To investigate whether amino acids (AAs) have similar actions, we determined the effects of an intravenously infused mixture of 15 AAs on carbohydrate disposal during euglycemic-hyperinsulinemic clamps associated with either basal or high glucagon concentrations in healthy male volunteers. Plasma glucose concentration was clamped at approximately 4.7 mM (coefficient of variation 4.7%). Insulin infusion (7.18 pmol.kg-1.min-1) raised serum insulin concentrations from 36-50 pM to between 300 and 600 pM. AA infusions (0.5 g.kg-1.h-1.4 h) raised plasma alpha-amino N2 concentrations about five- to six-fold. Infusion of AAs, somatostatin (somatotropin release inhibitory factor, SRIF), and high-glucagon replacement (3.0 ng.kg-1.min-1) reduced the rate of exogenous glucose infusion needed to maintain euglycemia from 51.1 +/- 7.2 mumol.kg-1.min-1 (saline + SRIF + high glucagon) to 28.3 +/- 11.1 mumol.kg-1.min-1 and stimulated endogenous glucose production (from 0 to approximately 17 mumol.kg-1.min-1). Thus, glucose disposal (exogenous infusion plus endogenous production of glucose) remained essentially unchanged. During infusion of AAs + SRIF + basal glucagon replacement (0.25 ng.kg-1.min-1), endogenous glucose production remained completely suppressed, and the rates of exogenous glucose infusion did not change (compared with saline + SRIF + basal glucagon replacement). The data showed that 1) hyperaminoacidemia associated with hyperglucagonemia stimulated endogenous glucose production despite hyperinsulinemia, and 2) intravenous infusion of a mixture of 15 AAs had no inhibitory effect on insulin-stimulated total-body glucose disposal.
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PMID:Effects of amino acids on glucose disposal. 197 39

The effects of ATP and ADP structural analogues (2-methylthio ATP; alpha,beta-methylene ADP) on somatostatin secretion were tested in dogs. Insulin and glucagon secretion was also evaluated. Our experiments were performed in vivo and in vitro. In vivo, 2-methylthio ATP was infused directly into the pancreaticoduodenal artery of anesthetized dogs and blood was sampled from the pancreaticoduodenal vein. This ATP analogue (approximately 15 microM) immediately induced stimulation of both somatostatin and insulin secretion, which was accompanied by a slight reduction of glycemia. A delayed increase in glucagon output was observed. In vitro, using the isolated perfused dog pancreas uncinate process, alpha,beta-methylene ADP, a stable ADP analogue (16.5 microM), was infused in the presence of a substimulating glucose concentration (4.2 mM). Under these conditions, alpha,beta-methylene ADP immediately induced the stimulation of somatostatin secretion without affecting basal insulin and glucagon secretion. In conclusion our results suggest the presence of P2 purinoceptors on pancreatic somatostatin secreting cells.
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PMID:P2 purinoceptor agonists stimulate somatostatin secretion from dog pancreas. 197 83

The plasma levels of somatostatin-like immunoreactivity, growth hormone and insulin were measured using a RIA method in healthy volunteers every 4h during the day and every 2h at night, without waking the subjects. In the waking state the fluctuation of plasma somatostatin-like immunoreactivity level only occurred near to meal time. A marked episodic surge of plasma SLI (peak value, 127.25 +/- 4.40 pg/ml (mean +/- ES)) was noted at 0200 in the initial period of slow wave sleep (SWS) 2h after the peak of GH. Insulin showed no sharp peak and its pattern was unrelated to other two hormones studied. A positive correlation was observed between SLI and GH in plasma using the mean cosinor method: the acrophase of SLI was at 0018 about 1h later than GH (at 2315). The acrophase of insulin occurred at 1525, significantly different as compared with the previous two. From these findings, it is concluded that SLI in peripheral plasma fluctuates with a significant circadian rhythm and a nychthemeral maxima as GH and that, whatever its source, that it is related to plasma GH and not to plasma insulin.
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PMID:Circadian variations of plasma somatostatin levels in healthy subjects. 197 63


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