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)

GH has been implicated in the pathophysiology of various acute and chronic complications of diabetes mellitus. As a consequence, there has been a great deal of interest in developing methods for suppressing GH secretion in diabetes. SMS 201-995 is a long-acting somatostatin analog which inhibits the secretion of numerous hormones, including GH. To determine the metabolic and hormonal responses to SMS 201-995 independent of endogenous insulin suppression, we studied six patients with insulin-dependent diabetes mellitus while they received 150 micrograms SMS 201-995, sc, daily for an 8-week period. This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04). The 24-h profiles of blood lactate, plasma free insulin, glucagon, FFA, blood glycerol, and beta-hydroxybutyrate were unchanged, whereas that of blood alanine increased significantly (7.8 +/- 0.4 to 10.6 +/- 0.9 mmol/L.h; P = 0.01). GH secretion declined in five of the six patients; the mean values before and during SMS 201-995 treatment were 102 +/- 23 and 68 +/- 12 micrograms/L.h, respectively (P = NS), for the six patients. [In the five patients in whom GH secretion declined, the mean values before and during SMS 201-995 treatment were 115 +/- 23 and 63 +/- 14 micrograms/L.h, respectively (P = 0.01).] These results suggest that SMS 201-995 may be administered to patients with insulin-dependent diabetes mellitus without a deleterious effect on metabolic control.
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PMID:The effects of SMS 201-995 (sandostatin) on metabolic profiles in insulin-dependent diabetes mellitus. 264 88

To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol at basal levels, and glucose was infused, whenever needed, to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. Isolated lack of cortisol increase caused a approximately 22% decrease in hepatic glucose production (P less than 0.01) and a approximately 15% increase in peripheral glucose utilization (P less than 0.01), which resulted in greater hypoglycemia (37 +/- 2 vs. 52 +/- 2 mg/dl, P less than 0.01) despite compensatory increases in plasma epinephrine. Lack of cortisol response also reduced plasma free fatty acid, beta-hydroxybutyrate, and glycerol concentrations approximately 50%. We conclude that cortisol normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.
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PMID:Contribution of cortisol to glucose counterregulation in humans. 266 16

With the aim of assessing a new somatostatin analogue to prevent the metabolic changes induced by a 6-h nocturnal arrest of an insulin pump, nine C-peptide negative Type 1 (insulin-dependent) diabetic patients were submitted blindly to two interruptions (from 23.00 to 05.00 hours) of their continuous s.c. insulin infusion, once after a single s.c. injection at 23.00 hours of 50 micrograms SMS 201-995 (Sandostatin, Sandoz) and once after 0.9% NaCl. Plasma SMS 201-995 levels peaked at 24.00 hours and then declined with an elimination half-life averaging 144 +/- 15 min. Plasma glucagon and growth hormone levels were significantly reduced after SMS 201-995 whereas the progressive fall in plasma-free insulin levels from 23.00 to 05.00 hours was unaffected. In the control test, blood glucose levels tended to decrease slightly from 23.00 to 02.00 hours and then increased markedly from 02.00 to 05.00 hours (+5.3 +/- 1.5 mmol/l) while after SMS 201-995 they decreased significantly from 23.00 to 02.00 hours (-2.6 +/- 0.5 mmol/l), resulting in values below 3 mmol/l in seven subjects, but showed a secondary increase until 05.00 hours (+3.5 +/- 1.5 mmol vs 23.00 h; p less than 0.05 vs 0.9% NaCl). While the rises in plasma non-esterified fatty acid and glycerol levels were not reduced by SMS 201-995, the increase in plasma 3-hydroxbutyrate levels, although similar from 23.00 to 02.00 hours, was significantly reduced from 02.00 to 05.00 hours (+77 +/- 20 vs +124 +/- 31 mumols.l-1.h-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sandostatin, a new analogue of somatostatin, reduces the metabolic changes induced by the nocturnal interruption of continuous subcutaneous insulin infusion in type 1 (insulin-dependent) diabetic patients. 268 64

Neuroglucopenia (NGP), which is a serious potential hazard for all insulin-treated diabetics, stimulates many neural and hormonal responses including increased glucagon secretion and activation of beta-adrenergic receptors of the autonomic nervous system. To determine which of these responses is important in recovery from NGP, we induced NGP in baboons by the intravenous (IV) injection of 2-deoxy-D-glucose with and without beta-adrenergic blockade (propranolol) and somatostatin. Thirty minutes after the induction of NGP the animals recovered, and the mean (+/- SEM) rise in arterial plasma glucose was 6.6 +/- 0.9 mmol/L, in glycerol 0.106 +/- 0.22 mmol/L, and in beta-hydroxybutyrate 0.091 +/- 0.22 mmol/L. Animal recovery and glucose rise were uninfluenced by the infusion of propranolol (mean 30 minute plasma glucose rise of 6.2 +/- 0.8 mmol/L) and somatostatin (6.8 +/- 0.8 mmol/L). However, the combined infusion of somatostatin and propranolol prevented animal recovery and glucose rise (1.0 +/- 0.1 mmol/L). The glycerol and beta-hydroxybutyrate rises were blocked by the propranolol infusion alone. Thus, recovery from NGP and the associated rise in plasma glucose, glycerol, and beta-hydroxybutyrate are prevented by the combination of the suppression of the glucagon and beta-adrenergic response to NGP. Furthermore, if the results of our study are extrapolated to insulin-dependent diabetic patients, most of whom have an impaired glucagon response to insulin-induced hypoglycemia/neuroglucopenia, they would be critically dependent on beta-adrenergic mechanisms for recovery from NGP.
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PMID:Glucose counterregulation during recovery from neuroglucopenia: which mechanism is important? 285 49

A peptide, eluted with cytochrome c, called 'big' somatostatin, is the only somatostatin-like immunoreactivity present in the peripheral plasma of the duck. The metabolic action of partially purified fractions of 'big' somatostatin was investigated on glucagon-stimulated lipolysis in chicken adipocytes. Significant inhibition of glycerol release (an index of lipolysis) induced by physiological concentrations of glucagon was observed with physiological concentrations of 'big' somatostatin; the percentage of inhibition was dose-dependent.
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PMID:The biological activity of duck 'big' somatostatin on chicken adipose tissue. 285 95

The linear and cyclic forms of vertebrate somatostatin were injected to worker honeybees at the rate of 50 ng per individual, and their effects on the lipemia were compared between themselves and with those of saline injection over a 3 hrs period. Both hormonal forms elicit a global decrease of the levels of phospholipids, steroids, fatty acids, diacyl and triacyl glycerol, by contrast with hyperlipemic effects induced by the injection of saline alone. The kinetics of variations show a remarkable phase concordance between the respective effects of both hormonal forms, with strong positive correlations in the case of phospholipids, fatty acids and glycerides. The linear and cyclic forms of somatostatin thus show similar effects counteracting the results of the release of endogenous hormones following the stress associated to the microsyringe stinging.
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PMID:[Comparative biochemical effects of the injection of cyclic and linear forms of vertebrate somatostatin on the honeybee in vivo. II. Blood lipids]. 287 Jul 85

The in vivo effect of glucose per se on blood ketone bodies, glycerol, and nonesterified fatty acids (NEFA) has been investigated in five normal (60 hours fasted) men receiving a somatostatin (SRIF) infusion (500 micrograms/h-1). When glycemia was raised over 10 mmol/L for 180 minutes by exogenous IV glucose infusion, neither insulin nor C peptide increase. NEFA and glycerol returned to fasting value in 40 minutes and remained stable. Ketone bodies decreased continuously and were significantly below the fasting values at the end of the study (1.3 +/- 0.3 mmol/L v 2.2 +/- 0.4 mmol/L, P less than 0.05). In order to ascertain whether glucose has been acting only on lipolysis or also on the liver ketogenic capacity, its effect was studied in vitro on isolated liver cells from 24-hour starved rats incubated with various amounts of palmitate. Glucose (30 mmol/L) did not affect the maximal ketogenic capacity (80 mumol/g (w/w)/h) measured with 1.6 mmol/L palmitate but increased the apparent palmitate K 0.5 for ketogenesis from 0.16 to 0.3 mmol/L. At physiologic free fatty acids concentration (0.22 mmol/L), glucose decreased ketogenesis by 90%. The effect was time-dependent, maximum after 30 minutes of incubation. Half-maximum inhibition by glucose was obtained at 6 mmol/L, a concentration at which lactate production was unaffected. These results suggest that glucose per se inhibits ketogenesis in vivo by acting probably both on lipolysis and on liver ketogenic capacity.
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PMID:Antiketogenic effect of glucose per se in vivo in man and in vitro in isolated rat liver cells. 287 99

We studied the influence of hyperglycemia on glucose homeostasis in man by determining the effect of graded hyperglycemia on peripheral glucose uptake and systemic metabolism in the presence of basal and increased serum insulin concentrations in 10 normal men. This was achieved by the simultaneous application of forearm and clamp techniques (euglycemic and hyperglycemic) during the combined iv infusion of somatostatin, glucagon, and insulin. While mean (+/- SE) basal serum insulin levels (14 +/- 2 microU/ml) were maintained, the elevation of fasting arterial glucose concentrations (90 +/- 1 mg/dl) to 146 +/- 1 and 202 +/- 1 mg/dl (each for 120 min) increased forearm glucose uptake (FGU) only modestly from 0.06 +/- 0.01 to 0.15 +/- 0.02 and then to 0.24 +/- 0.03 mg/100 ml forearm X min, respectively. During physiological hyperinsulinemia (47 +/- 3 microU/ml), the influence of similar graded hyperglycemia on FGU was considerably enhanced. At plasma glucose concentrations of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, FGU rose to 0.33 +/- 0.05, 0.59 +/- 0.07, and 0.83 +/- 0.12 mg/100 ml forearm X min, respectively. The glucose infusion rate required to maintain the glucose clamp with basal insulin levels was 1.08 +/- 0.20 and 2.67 +/- 0.39 mg/kg X min at glucose concentrations of 146 +/- 1 and 202 +/- 1 mg/dl, respectively. During physiological hyperinsulinemia, however, the glucose infusion rate required was 4.15 +/- 0.39, 9.45 +/- 1.05, and 12.70 +/- 0.81 mg/kg X min at glucose levels of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, respectively. Lactate concentrations rose significantly during hyperglycemia, but the rise in the presence of increased insulin concentrations (from 0.72 +/- 0.06 to 1.31 +/- 0.11 mmol/liter; P less than 0.001) considerably exceeded the increment (from 0.74 +/- 0.05 to 0.92 +/- 0.03 mmol/liter) with basal insulin levels. While both FFA and glycerol concentrations were immediately reduced by euglycemic hyperinsulinemia, the fall in FFA during hyperglycemia in the presence of basal insulin levels preceded the decrease in glycerol concentrations by 45 min. Forearm oxygen consumption did not change throughout the study.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The influence of graded hyperglycemia with and without physiological hyperinsulinemia on forearm glucose uptake and other metabolic responses in man. 287 53

Long-acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201-995, 50 micrograms, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201-995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201-995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201-995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3-hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side-effects. SMS 201-995, 50 micrograms, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects.
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PMID:Effects of somatostatin analogue SMS 201-995 in normal man. 287 47

We have used primed constant infusions of [1-13C]palmitic acid, [2-3H]glycerol, and [U-14C]glucose to evaluate the response of glucose and fat kinetics to alpha or beta adrenergic blockade in conscious dogs. The response of each blocking agent was evaluated both with and without control of the glucoregulatory hormones. When hormones were controlled, somatostatin and metyrapone were infused to block hormonal secretion, and insulin, glucagon, growth hormone, and cortisol were replaced at basal physiological rates. alpha blockade (beta stimulation) did not influence glucose production or oxidation, but it did decrease glucose clearance when hormones were controlled. Clearance did not decrease during blockade when hormones were not controlled, presumably because of the resulting increase in the plasma insulin concentration. Glucose production, plasma glucose concentration, and glucose oxidation all increased with beta blockade (alpha stimulation). alpha blockade (beta stimulation) resulted in an increase in lipolysis, whereas beta blockade (alpha stimulation) resulted in a decrease in lipolysis. In neither case, however, did FFA oxidation change. We conclude that (a) the predominant effect of unopposed stimulation is the stimulation of lipolysis, whereas unopposed alpha stimulation inhibits lipolysis. Direct effects of either alpha or beta stimulation on glucose kinetics are less dramatic, but both alpha and beta stimulation decrease glucose clearance.
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PMID:The integrated effect of adrenergic blockade on glucose, fatty acid, and glycerol kinetics: responses in the basal state and during hormonal control with somatostatin-hormonal infusion. 288 Oct 26


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