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)

Infusion of somatostatin, an inhibitor of glucagon secretion, in insulin-dependent diabetics resulted in a 75-100% reduction in the blood-glucose rise after oral glucose administration, but did not improve intravenous glucose tolerance. Somatostatin reduced blood-xylose levels by 50-90% after ingestion of this pentose and delayed the peak increment in blood-xylose by 1-2 h. Similar effects on blood-xylose levels and a 30% reduction in splanchnic blood-flow were observed in normal subjects during infusion of somatostatin. Glucagon administration (3 ng per kg per min) or intraduodenal administration of xylose did not reverse somatostatin's effect on xylose tolerance. Somatostatin reduces postprandial hyperglycaemia in diabetes primarily by decreasing and/or delaying carbohydrate absorption rather than enhancing carbohydrate disposal. This effect may be mediated, in part, but a reduction in splanchnic blood-flow. These findings indicate that postprandial hyperglycaemia in diabetes is due primarily to insulin deficiency rather than glucagon excess.
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PMID:Influence of somatostatin on carbohydrate disposal and absorption in diabetes mellitus. 6 40

Oral carbohydrate tolerance tests with xylose, galactose and lactose were performed. After an interval of at least 24 h the same tests were repeated following an i.v. bolus and during infusion of somatostatin. Somatostatin does not influence xylose absorption. However, absorption of galactose and lactose is significantly reduced (p less than 0.01/0.008) during somatostatin infusion. On the other hand, serum levels of galactose remain unchanged despite administration of somatostatin, when galactose is given parenterally. The results support the assumption that the absorption process in small intestine is affected by somatostatin. Possible effects of somatostatin on hormones regulating the intestinal absorption and on energy-depending carrier mechanisms are discussed.
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PMID:Influence of somatostatin on carbohydrate absorption in human small intestine. 43 79

Somatostatin was infused via the portal vein at a rate of 50 ng/min in a group of eight conscious dogs beginning 30 min before and continuing for 6 h after the ingestion of an 800-g fat-protein meal. The fasting and postprandial levels of plasma somatostatin-like immunoreactivity (SLI), insulin, glucagon, and triglycerides were compared with those during an intraportal infusion of saline as a control. In both groups, SLI rose significantly within 15 min of the ingestion of the meal, but during somatostatin infusion, mean peripheral vein levels of SLI ranged from 30-85 pg/ml above those of the saline control experiments. The postprandial rise in plasma triglycerides was reduced significantly below the control values at all points between 75-270 min, and this reduction was the result of lowered chylomicron levels. Neither fasting nor postprandial insulin or glucagon levels were significantly reduced by the somatostatin infusion. Intraportally infused somatostain also reduced portal vein xylose levels after an intragastric xylose load. The results are compatible with, but do not prove, a physiological role for somatostatin in the homeostasis of ingested nutrients.
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PMID:Evidence for a role of splanchnic somatostatin in the homeostasis of ingested nutrients. 44 90

Food intake results in a variety of responses, with the autonomic nervous system playing an important role in maintaining cardiovascular homeostasis. In patients with autonomic failure, who have severe sympathetic impairment, food substantially lowers blood pressure even in the supine position. This is related to a marked increase in splanchnic blood flow, without compensatory changes in the rest of the circulation. Of the food components, glucose causes similar effects to food, while an isosmotic, isocaloric load of the inert carbohydrate, xylose, causes only a small fall in blood pressure. Lipid causes a small, short-lived fall in blood pressure and protein causes minimal change. Insulin appears to contribute to the fall in blood pressure, as bolus injections of insulin (even before ensuing hypoglycaemia), or insulin infusions (with an euglycaemic clamp), when given intravenously lower blood pressure. Other vasodilatatory gut peptides released by food may also play a role. The somatostatin analogue, Octreotide (SMS 201-995), which inhibits the release of a range of peptides, prevents both glucose and food-induced hypotension. Studies of the mechanisms responsible for post-prandial hypotension in autonomic failure continue to provide insight into the relationship between food intake and the hormonal, peptidergic and neural responses which affect the cardiovascular system.
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PMID:Effect of food intake on cardiovascular control in patients with impaired autonomic function. 197 48

To assess the pharmacologic properties and possible use in the treatment of diabetes mellitus of a recently developed analogue somatostatin (L-363,586), the analogue (2, 5, 10 or 40 micrograms/hr), somatostatin (200 micrograms/hr), or placebo were infused intravenously for 5 hours in 6 insulin-dependent diabetic subjects who were given a standard meal containing xylose. The metabolic clearance rate of the analogue (approximately 300 ml/min) was 1/6 that previously reported for somatostatin (approximately 2000 ml/min) and its half-life was approximately 20 times as great as that reported for somatostatin (45 vs 2 min). At a dose of 10 micrograms/hr, the analogue produced suppression of plasma glucagon, growth hormone, glucose, xylose and triglyceride responses to meal ingestion which were comparable to those observed when somatostatin was infused at a rate of 200 micrograms/hr. We conclude that L-363,586 is a long-acting and potent analogue of somatostatin, which has the potential for use as an adjunct to insulin in the treatment of diabetes mellitus.
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PMID:Efficacy, pharmacokinetics and tolerability of a somatostatin analogue (L-363,586) in insulin-dependent diabetes mellitus. 287 69

The effect of the long-acting somatostatin analogue Sandostatin (SMS 201-995) on intestinal absorption and propagation (mouth-to-caecum transit time; MCTT), on pancreatic secretion and on gall bladder contraction after direct (secretin-pancreozymin test) and indirect stimulation (Lundh meal), and on meal-induced responses of seven gastrointestinal regulatory peptides has been investigated. In a double-blind cross-over study, 9 healthy volunteers completed two 7-day periods with subcutaneous injections of either placebo or 25 micrograms SMS 201-995 twice daily. Mean faecal fat excretion was increased to 19.2 g/day and MCTT was three times longer during the SMS period. After duodenal infusion of a mixture containing D-galactose, D-xylose and triglycerides, SMS 201-995 significantly reduced the serum concentrations of D-galactose but increased serum levels of D-xylose. After 6 days of pretreatment, SMS 201-995 completely suppressed duodenal trypsin, lipase and bilirubin increases in response to endogenous stimulation by a Lundh meal. Concomitantly, cholecystokinin (CCK) release and gall bladder contraction were almost abolished. Compared with placebo, SMS 201-995 significantly diminished pancreatic amylase, trypsin and lipase output after stimulation with CCK, while the secretion of fluid and bicarbonate in response to secretin was unchanged. This inhibition of enzyme response was significantly more marked after a single injection of the analogue than after pretreatment for 7 days and did not reach the level of exocrine pancreatic insufficiency. CCK-induced gall bladder contraction was significantly inhibited by a single dose of 25 micrograms SMS 201-995 but not after 7 days of pretreatment with the somatostatin analogue.
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PMID:Effect of the somatostatin analogue sandostatin (SMS 201-995) on gastrointestinal, pancreatic and biliary function and hormone release in normal men. 288 60

We investigated in 6 acromegalic patients the acute effects on glucose tolerance and insulin secretion of a single sc injection of the somatostatin analogue SMS 201-995, performed 4 h before a mixed meal with xylose administration. Growth hormone levels decreased from 34.0 +/- 20.3 (mean +/- SE) to a minimum of 9.3 +/- 3.0 ng/ml, 3 1/2 h after the injection. A significant inhibition of insulin secretion was also noticed, with a fall from 25.3 +/- 6.4 to 6.3 +/- 2.3 microU/ml at 1 h, and a lower and delayed peak level after the mixed meal. However, the postprandial plasma glucose increase was not different from a control day, while plasma xylose levels were lower. Mean glucagon level after SMS 201-995 was lower than control value in 3 out of the 4 patients in whom it was determined. The decrease of serum growth hormone levels, together with partial glucagon inhibition and, more important, a slowing of intestinal absorptive processes, counterbalanced the inhibitory action of SMS 201-995 on insulin secretion, and no deterioration in carbohydrate tolerance could be demonstrated. However, before SMS 201-995 is employed in the management of acromegalic patients refractory to surgery and bromocriptine therapy, we need further observations of postprandial glycemic profiles during long-term therapy with multiple daily injections of the compound.
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PMID:Effect of a new long-acting somatostatin analogue (SMS 201-995) on glycemic and hormonal response to a mixed meal in acromegalic patients. 289 7

Five type II diabetic patients were studied after secondary failure of oral agents, with and without the addition of the new long-acting somatostatin analogue SMS 201-995 to an intermediate-acting insulin regimen. SMS 201-995 was administered twice daily, before breakfast and dinner, as 100 micrograms sc injections, and resulted in a lowering of plasma glucose, as well as of plasma glucagon and serum C-peptide levels. SMS 201-995 abolished postprandial glycemic and xylosemic peaks related to meals and to oral d-xylose when they were taken shortly after the administration of the analogue, while it had no effect on glycemic and xylosemic increments that followed the midday meal. The new somatostatin analogue improves glucose tolerance in type II diabetic patients, both by inhibiting counterregulatory hormones and by delaying and reducing intestinal absorption of nutrients. Its administration could lead to a reduction of daily insulin requirements. Our findings indicate that SMS 201-995 may have a role as an adjunct to insulin in the management of type II diabetic patients after secondary failure of oral agents.
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PMID:Effect of a new long-acting somatostatin analogue (SMS 201-995) on glycemic and hormonal profiles in insulin-treated type II diabetic patients. 304 68

This study was undertaken to elucidate the mechanism(s) involved in glucocorticoid-induced insulin antagonism. Male Sprague-Dawley rats (200 to 210 g) were injected with 1 mg/kg dexamethasone-phosphate (Dex) or the vehicle every other day for 10 days. Two days after the last injection, fasted anesthetized animals were infused (per kg body weight per min) with 8 mg glucose, 5 mU porcine insulin and 1.4 micrograms somatostatin with blood sampling before, and at 10 min intervals between 90 and 130 min after the pancreatic suppression test was begun. At the end of the test, abdominal muscle was quickly freeze-clamped and the substrate and products of the rate-determining reactions of glycolysis and glycogenesis were measured. Dex-treated rats had higher basal (0 min) and steady-state levels (90-130 min) of both glucose and insulin signifying insulin antagonism. The pattern of muscle tissue metabolites revealed no free intracellular glucose in either group and concentrations of all other metabolites in the Dex-treated rats were less than those in the control animals (except for a small increase in glycogen). These results suggest a site of insulin antagonism between (and including) insulin binding and glucose transport. Further studies in the Dex-treated rats revealed normal: a) insulin binding to freshly isolated hepatocytes; b) basal and insulin-stimulated xylose transport in soleus muscle; c) basal and insulin-stimulated glucose uptake in hemidiaphragms. These normal in-vitro results suggested that a circulating factor may be responsible. Repeat pancreatic suppression tests in the Dex-treated rats revealed blunted suppression of serum FFA concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible role for the glucose-fatty acid cycle in dexamethasone-induced insulin antagonism in rats. 330 80

Five insulin treated diabetics were studied on three consecutive days. Overnight variable intravenous insulin infusions were used before each study to maintain normoglycaemia and to calculate the optimal basal insulin infusion rate (1.1 +/- 0.1 U/h) which ws then kept constant throughout the study day. A standard 400 kCal breakfast with 25 g xylose was given at 0800 h. When the blood glucose rose above 4.1 mmol/l, an external artificial pancreas was used to infuse either extra insulin (day INS) or somatostatin for either 3h (day som) or the entire 8h experimental period (day SOM). Peak post-prandial blood glucose values were similar on all three days. The blood glucose rebounded after the cessation of the somatostatin infusion on day som. Post-prandial blood xylose peaks were lowered by somatostatin on both days but rebounded after the cessation of the somatostatin infusion on day som. The area under the plasma and urinary xylose curves was lowered by somatostatin only on day SOM. Growth hormone and glucagon levels were not statistically different on all 3 days. Thus somatostatin, when added to an optimal insulin infusion, minimised the insulin requirements by slowing intestinal absorption, but led to rebound hyperglycaemia if not feed-back controlled.
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PMID:Effects of somatostatin added to insulin in a glucose-controlled insulin infusion system. 611 91


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