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

Serum concentrations of immunoreactive pancreatic polypeptide (IR-PP) were measured in dogs in response to a meal and to intraduodenal infusions of amino acids, Na oleate, and HCl. In addition, the effects of somatostatin on meal-stimulated IR-PP concentrations were studied. In response to a meal, IR-PP rose from 151 +/- 19 pg/ml to 296 +/- 35 pg/ml (P less than 0.01) at 15 min, reached a plateau of 367 +/- 56 pg/ml at 45 min, and remained elevated for 4 h. In response to intraduodenal amino acids, IR-PP rose from 196 +/- 22 pg/ml to 342 +/- 19 pg/ml (P less than 0.01), and serum alanine rose from 251 +/- 18 mM to 361 +/- 30 mM. Peak concentrations of IR-PP, however, were reached before alanine rose above baseline. During administration of intraduodenal Na oleate, IR-PP rose from 181 +/- 21 pg/ml to 348 +/- 17 pg/ml (P less than 0.01). Intraduodenal HCl had no effect on IR-PP. Intravenous somatostatin (100 microgram/h) suppressed meal-stimulated IR-PP from 450 +/- 68 pg/ml to 133 +/- 23 pg/ml (P less than 0.01). The data indicate 1) IR-PP is increased after a meal and intraduodenal administration of amino acids and Na oleate; 2) the increases in serum IR-PP precede increases in serum levels of absorbed alanine; and 3) somatostatin suppresses the meal-stimulated increase in serum IR-PP.
 ...
PMID:Pancreatic polypeptide responses to a meal and to intraduodenal amino acids and sodium oleate. 74 98

To evaluate the role of glucagon in the pathogenesis of diabetic ketoacidosis in man, we studied the effect of suppression of glucagon secretion by somatostatin on changes in plasma beta-hydroxybutyrate and glucose concentrations (as well as changes in their precursors) after acute withdrawal of insulin from seven patients with juvenile-type diabetes. Suppression of glucagon secretion prevented the development of ketoacidosis for 18 hours after acute insulin withdrawal, whereas in control studies mild ketoacidosis occurred 10 hours after insulin was stopped. Plasma beta-hydroxybutyrate, glucose, free fatty acid, and glycerol levels were all markedly lower during suppression of glucagon secretion (p smaller than 0.001), whereas plasma alanine levels were higher (p smaller than 0.001). These studies indicate that insulin lack per se does not lead to fulminant diabetic ketoacidosis in man and that glucagon, by means of its gluconeogenic, ketogenic, and lipolytic actions, is a prerequisite to the development of this condition.
 ...
PMID:Prevention of human diabetic ketoacidosis by somatostatin. Evidence for an essential role of glucagon. 80 37

Somatostatin and dihydrosomatostatin (H2somatostatin) are equipotent in inhibiting insulin and glucagon release induced by arginine in the rat. The ID50 of H2somatostatin on insulin and glucagon secretion induced by arginine are 14 +/- 6 and 6 +/- 10 mug/100 g BW respectively, similar to the ID50 of H2somatostatin (18 +/- 10 mug/100 g BW) on inhibition of insulin release induced by glucose. Thyrotropin releasing factor, luteinizing hormone releasing factor, alpha-MSH, and the N-terminus decapeptide of the beta-chain of porcine hemoglobin did not alter the secretion of insulin and glucagon induced by arginine. With the exception of [Ala2[-somatostatin and [Ala5]-somatostatin, alanine substituted analogs of somatostatin were less potent than somatostatin. [D-Trp8]-somatostatin is 6-8 times as potent as somatostatin in inhibiting insulin and glucagon release induced by arginine. The relative potencies of these analogs to inhibit the secretion of the pancreatic hormones are in good agreement with our previously reported values based on the inhibition of GH secretion in vitro.
 ...
PMID:Biological activity of somatostatin and somatostatin analogs on inhibtion of arginine-induced insulin and glucagon release in the rat. 81 91

To study the individual effects of glucagon and growth hormone on human carbohydrate and lipid metabolism, endogenous secretion of both hormones was simultaneously suppressed with somatostatin and physiologic circulating levels of one or the other hormone were reproduced by exogenous infusion. The interaction of these hormones with insulin was evaluated by performing these studies in juvenile-onset, insulin-deficient diabetic subjects both during infusion of insulin and after its withdrawal. Infusion of glucagon (1 ng/kg-min) during suppression of its endogenous secretion with somatostatin produced circulating hormone levels of approximately 200 pg/ml. When glucagon was infused along with insulin, plasma glucose levels rose from 94 +/- 8 to 126 +/- 12 mg/100 ml over 1 h (P less than 0.01); growth hormone, beta-hydroxy-butyrate, alanine, FFA, and glycerol levels did not change. When insulin was withdrawn, plasma glucose, beta-hydroxybutyrate, FFA, and glycerol all rose to higher levels (P less than 0.01) than those observed under similar conditions when somatostatin alone had been infused to suppress glucagon secretion. Thus, under appropriate conditions, physiologic levels of glucagon can stimulate lipolysis and cause hyperketonemia and hyperglycemia in man; insulin antagonizes the lipolytic and ketogenic effects of glucagon more effectively than the hyperglycemic effect. Infusion of growth hormone (1 mug/kg-h) during suppression of its endogenous secretion with somastostatin produced circulating hormone levels of approximately 6 ng/ml. When growth hormone was administered along with insulin, no effects were observed. After insulin was withdrawn, plasma beta-hydroxybutyrate, glycerol, and FFA all rose to higher levels (P less than 0.01) than those observed during infusion of somatostatin alone when growth hormone secretion was suppressed; no difference in plasma glucose, alanine, and glucagon levels was evident. Thus, under appropriate conditions, physiologic levels of growth hormone can augment lipolysis and ketonemia in man, but these actions are ordinarily not apparent in the presence of physiologic levels of insulin.
 ...
PMID:Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin. 82 Jul 17

Cyclic somatostatin was administered intravenously (10 mug/min for 60 min) to 10 healthy overnight fasted (postabsorptive) subjects and to 5 healthy 60-h fasted subjects. In both groups, arterial insulin and glucagon fell 50% and splanchnic release of these hormones was inhibited. In the overnight fasted subjects splanchnic glucose output fell 70%, splanchnic uptake of lactate and pyruvate was unchanged, alanine uptake fell by 25%, and glycerol uptake rose more than twofold in parallel with an increase in arterial glycerol. In the 60-h fasted group splanchnic glucose output was less than 40% of that observed in the overnight fasted subjects. Somatostatin led to a further decrease (--70%) in glucose production. Splanchnic uptake of lactate and pyruvate fell by 30-40%, amino acid uptake was unchanged, while uptake of glycerol rose fivefold. Total uptake of glucose precursors thus exceeded the simultaneous glucose output by more than 200%. Splanchnic uptake of FFA rose fourfold during somatostatin while output of beta-hydroxybutyrate increased by 75%. Estimated hepatic blood flow fell 25-35% and returned to base line as soon as the somatostatin infusion ended. It is concluded that (a) somatostatin-induced hypoglucagonemia results in inhibition of splanchnic glucose output in glycogen-depleted, 60-h fasted subjects as well as in postabsorptive subjects, indicating an effect of glucagon on hepatic gluconeogenesis as well as glycogenolysis; (b) the glucagonsensitive step(s) in gluconeogenesis affected by somatostatin involves primarily intra-hepatic disposal rather than net hepatic uptake of glucose precursors; (c) splanchnic uptake of fatty acids and ketone output are increased in the face of combined insulin and glucagon deficiency; and (d) diminished splanchnic blood flow may contribute to some of the effects of somatostatin on splanchnic metabolism.
 ...
PMID:Influence of somatostatin on splanchnic glucose metabolism in postabsorptive and 60-hour fasted humans. 83 77

Hormonal and metabolic effects of a synthetic linear somatostatin were tested in insulin-dependent subjects submitted to an intravenous arginine infusion. Arginine alone induced a rise in plasma growth hormone (HGH) and glucagon (IRG) concentrations but did not affect the spontaneous diurnal decrease of plasma cortisol; blood glucose concentration rose while that of alanine decreased suggesting enhanced gluconeogenesis; concentrations of plasma free fatty acids (FFA) and 3-hydroxybutyrate decreased. Somatostatin, at three different dosages, markedly influenced these patterns: HGH response to arginine was suppressed by the lowest somatostatin dose; IRG response was progressively inhibited by increasing doses of somatostatin but never reached zero; cortisol level was not decreased but slightly increased by somatostatin. Substrate responses to arginine were also modified by somatostatin: alanine disappearance was impaired, this effect being dose-related; plasma FFA and 3-hydroxybutyrate concentrations showed a significant increase rather than decrease, consistent with somatostatin suppression of residual insulin secretion. Tolerance to somatostatin was good and no alteration of hemostasis was observed.
 ...
PMID:Hormonal and metabolic effects of somatostatin in diabetic patients submitted to an i.v. arginine infusion. 87 Mar 53

Four analogs of ovine somatostatin (SRIF, PSOMATOTROPIN RELEASE INhibiting factor), the sequence of which is H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-trp-Lys-Thr-Phe-Thr-Ser-Cys-OH, have been synthesized by the solid-phase methodology. The compounds were assayed and were found to possess the following somatotropin release inhibiting potencies relative to pure synthetic somatostatin in vitro and in vivo, respectively: [Ala3,14]somatostatin, 0.6 and 2.0%; [SMe-Cys3,14]somatostatin, 4 and 0.6%; [NAc-Cys3]somatostatin, 39 and 105%; [des-Ala1-Gly2]somatostatin, 65 and 71%. The dihydrosomatostatin analogs [NAc-Cys3-H2]somatostatin and [des-Ala1Gly2-H2]somatostatin after two purifications by gel filtration were assessed to be at least 80% homogeneous and had respectively 99 and 89% of somatostatin potencied in vivo. Structure-activity relationships are discussed.
 ...
PMID:Somatostatin analogs. Relative importance of the disulfide bridge and of the Ala-Gly side chain for biological activity. 109 34

The effect of glucagon suppression by somatostatin upon endogenous hyperglycemia was studied in three forms of experimental insulin deficiency in dogs: alloxan diabetes, total pancreatectomy, and diazoxide administration. In six insulin-requiring alloxan-diabetic dogs deprived of insulin for 24 hr, mean plasma glucose declined to 77% +/- 6% of the baseline level of 350 +/- 41 mg/dl during 3 hr of glucagon suppression, significantly below the unsuppressed saline controls (p less than 0.01-0.05). When somatostatin was discontinued, glucagon rose and glucose increased 21% (p less than 0.05) in 30 min. Significant correlation between maximal changes in glucagon and glucose was observed (r = 0.81; p less than 0.001). Even during a 1-hr alanine infusion in such dogs, glucose declined an average of 36 +/- 9 mg/dl, instead of rising 51 +/- 7 mg/dl as in unsuppressed controls. Maximal changes in glucagon and glucose were correlated (r = 0.85; p less than 0.01). In eight depancreatized dogs pretreated intravenously with continuous insulin and glucose infusions, withdrawal of insulin was followed by a rise in extrapancreatic glucagon; mean plasma glucose rose from 212 +/- 43 to 415 +/- 80 mg/dl 270 min after the end of the insulin infusion. However, when glucagon was suppressed after insulin withdrawal, glucose remained below 240 mg/dl, significantly less than the controls (p less than 0.005); when somatostatin was stopped, glucagon rose and glucose increased 88 +/- 19 mg/dl within an hour. The rises in glucagon and glucose were significantly correlated (r = 0.68; p less than 0.05). Glucagon suppression by somatostatin during diazoxide-induced blockade of insulin secretion in four normal dogs reduced hyperglycemia significantly but did not prevent it. The results support the hypothesis that a relative or absolute excess of glucagon, as well as a relative or absolute deficiency of insulin, is etiologically important in the development of endogenous hyperglycemia in diabetes mellitus, the hyperglucagonemia probably mediating the glucose overproduction.
 ...
PMID:The role of glucagon in the pathogenesis of the endogenous hyperglycemia of diabetes mellitus. 118 99

The isolation and structure of somatostatin (GH-RIH) from pig hypothalami are described. This hormone was purified by preparative gel filtration, solvent extraction, countercurrent distribution in two solvent systems, ion-exchange and partition chromatography, and analytical gel filtration. The somatostatin activity was followed by in vitro bioassays and a radioimmunoassay. The isolated product was homogeneous chromatographically and had biological and immunological properties similar to synthetic somatostatin corresponding to the ovine hormone. The primary structure of porcine somatostatin was shown to be H-Ala-Gly-cyclo-(Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys)-OH. Other immunologically and biologically active form(s) of somatostatin were also detected.
 ...
PMID:Isolation and structure of somatostatin from porcine hypothalami. 125 9

Fasting hypoglycemia occurred in a patient with a histologically benign mesothelioma; the serum insulin was low (2-4 muU./ml.), as was the glucose utilization rate. Splanchnic glucose output was markedly decreased on direct measurement (21 mg./min.; normal: 108-180 mg./min.). Splanchnic uptake of gluconeogenic substrates plasma glucagon was low normal during hypoglycemia and responded poorly to oral and intravenous alanine. The nonsuppressible insulin-like (NSILA-s) and somatomedin-like activities of the serum were not elevated, and the tumor did not release insulin-like activity on incubation nor did it contain somatostatin. The marked decrease in splanchnic glucose output was the principal cause of hypoglycemia, was associated with an apparent decrease in glycogenolysis, and was at least partly due to deficient glucagon secretion. The relationship of the tumor to these defects is unclear. The tumor may have secreted an unknown insulin-like material affecting primarily the liver and/or pancreatic alpha cell. The approach used here may serve as a paradigm for the analysis of hypoglycemia not caused by excessive insulin.
 ...
PMID:Tumor hypoglycemia: deficient splanchnic glucose output and deficient glucagon secretion. 125 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>