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)

Epinephrine (0.1 micrograms.kg-1.min-1) was infused with or without somatostatin (0.1 microgram.kg-1.min-1) in six depancreatized dogs, studied under normo- and hypoinsulinemia to determine whether the participation of glucagon in epinephrine-induced hepatic glucose overproduction is governed by the degree of metabolic control. When normoglycemia was achieved by basal intraportal insulin replacement, insulin levels remained constant during the epinephrine infusion, and there was a twofold increase in extrapancreatic immunoreactive glucagon (eIRG) and glucose production (Ra). Although eIRG increments were prevented by somatostatin, the increase in Ra was undiminished, indicating that epinephrine can act independently of glucagon as in normal animals. During subbasal intraportal insulin infusion in the depancreatized dogs, insulin levels remained 35% lower than with basal replacement, and the animals were hyperglycemic. Epinephrine induced a similar twofold increase in eIRG as during normoglycemia, and again this rise was prevented by somatostatin. There was a significantly greater, threefold increase in Ra with epinephrine when the animals were hyperglycemic. This exaggerated response to epinephrine was not seen during eIRG suppression by somatostatin, suggesting that glucagon participated in the epinephrine-induced hepatic glucose overproduction when the depancreatized dogs were in poor metabolic control, as seen previously in alloxan-diabetic dogs. However, in the depancreatized, unlike in the alloxan-diabetic dogs, epinephrine-induced glucagon release was small. Thus, hypoinsulinemia appears to sensitize the liver to eIRG during epinephrine infusion. The fact that epinephrine induces hyperglycemia both in physiology and diabetes could indicate an important role in enhancing glucose transport in insulin-insensitive tissues.
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PMID:State of metabolic control determines role of epinephrine-glucagon interaction in glucoregulation in diabetes. 612 26

Murine mammary aplastic carcinoma, when it is passed from one alloxan-diabetic animal to another, after several passages becomes conditioned to hypoinsulinemia by secreting its own substance(s) immunologically cross-reactive with insulin (SICRI). Although not cytotoxic, the total daily dose of 2.5 mg of synthetic linear somatostatin per one kg body mass, administered in three or more portions, retards tumor growth in normoinsulinemic mice and the proliferation of tumors preconditioned by three serial passages in diabetics. After the first passage, somatostatin treatment has no effect on the already slow growth of the unconditioned tumor. Somatostatin-reduced tumor proliferation is accompanied by the strong suppression of insulin and SICRI levels, respectively; this effect is completely abolished by the administration of modest doses of crystalline insulin. It is concluded that somatostatin retards tumor growth by diminution of plasma levels of insulin and SICRI, respectively.
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PMID:Somatostatin-reduced proliferation of murine aplastic carcinoma conditioned to diabetes. 612 80

After mentioning insulin deficiency diabetes in animals produced by drugs such as Alloxan, Diazoxide or Streptozotocin only drugs are discussed, which are used in elderly patients and may either provoke diabetes mellitus (or temporary hyperglycemia) or may change the clinical course of diabetes. In the first group endocrine products such as corticosteroids, estrogens, somatotrophic hormone, thyroid hormone, glucagon, somatostatin, catecholamines and hormones with anabolic effects are listed. The second group comprises saluretics, salicylates, amphetamines, pentamidine, nicotinic acid and its derivatives, beta-receptor blockers and finally laxatives. Hypopotassemia alone can also be the cause of hyperglycemia. Speaking of the sulfonylureapreparations, their interaction with alcohol, with phenylbutazone, with some sulfonamides and the effect of the sulfonylureas on peripheric insulin-receptors is discussed. In case of severe diabetic vascular disease the use of anticoagulants may lead to hemorrhages. If such an hemorrhage occurs in the eyes, it may lead to blindness. In diabetic nephropathy the use of phenacetine and its derivatives should be substituted by another medication. This review is not at all complete but should only show some of the problems in the treatment of elderly diabetic patients.
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PMID:[Iatrogenic diabetes mellitus (side effects and interactions of drugs during clinical diabetes mellitus (author's transl)]. 612 38

Under normal conditions, glucose acutely influences pancreatic islet B, A and D cell secretion. In addition, prior exposure to glucose modulates the secretory responsiveness of these cells (priming effect). We have tested whether alloxan diabetes influences priming effects of glucose on A and D cell secretion. Rat pancreases were perfused 72 h after alloxan treatment. A 20 min infusion of 27.7 mmol/l of glucose failed to induce priming effects, i.e. it did not inhibit the glucagon nor amplify the somatostatin response to a subsequent (15 min later) infusion of 8 mmol/l of arginine. Insulin treatment in vivo for 48 h restored a priming effect of glucose on glucagon secretion in the perfused pancreas, i.e. exposure to 27.7 mmol/l of glucose now inhibited subsequent arginine-induced glucagon secretion by 48% relative to a stimulation period with arginine preceding the glucose pulse (from 5.0 +/- 0.7 to 2.6 +/- 0.5 ng/min, p less than 0.01). Conversely, insulin treatment in vivo did not restore a priming effect of glucose on somatostatin secretion. Other effects noted were failure of 27.7 mmol/l glucose to stimulate, during its presence, the release of somatostatin from pancreases of the diabetic rats whether untreated or insulin-treated. Furthermore, insulin treatment abolished the arginine-induced somatostatin secretion observed in pancreases from untreated rats. It is concluded that short-term alloxan diabetes leads to loss of a priming effect of glucose on glucagon secretion and that this abnormality is secondary to direct or indirect effects of insulinopenia. Concomittant abnormalities of glucose regulation of somatostatin secretion may, in part, be secondary to a cytotoxic effect of alloxan on the D cell.
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PMID:Loss of a priming effect of glucose on A and D cell secretion in perfused pancreases from alloxan-diabetic rats: role of insulin and alloxan. 613 Oct 6

The effect of glucagon at various infusion rates on plasma levels of somatostatin-like immunoreactivity (SLI) was examined in conscious normal and chronic alloxan diabetic dogs. In normal dogs glucagon infused at 6, 36, and 120 ng/kg per min did not affect the peripheral venous plasma SLI levels. In diabetic dogs, however, peripheral venous plasma SLI levels in inferior vena cava rose significantly from a mean base-line value of 181+/-9 pg/ml to a peak value of 279+/-38 pg/ml during the infusion of 120 mug/kg per min of glucagon, which raised plasma immunoreactive glucagon to >5,000 pg/ml. This glucagon-mediated increase was completely abolished by coinfusion of 7 mU/kg per min of insulin, a rate that maintained the ratio of insulin to glucagon at approximately the baseline value. In anesthetized normal dogs the concentration of SLI in the venous effluent of the pancreas, the gastric fundus and the antrum increased significantly with each infusion rate of glucagon using including the lowest rate of 4 ng/kg per min, which raised the plasma level of glucagon to 395+/-19 pg/ml. This stimulatory effect on SLI secretion was completely abolished by insulin coinfusion at a rate designed to maintain the insulin to glucagon ratio at approximately the baseline value, but the effect of a high 90-ng/kg per min infusion on pancreatic and gastric SLI release was not suppressed by coinfusion of 10 mU/kg per min insulin. These results suggest that glucagon stimulates splanchnic D cells unless insulin secretion is proportionally stimulated and suggests that the splanchnic D cell is a common target upon which the two hormones exert opposing actions. The loss of insulin inhibition of glucagon-mediated somatostatin secretion may account for the hypersomatostatinemia of severe diabetes.
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PMID:Opposing actions of glucagon and insulin on splanchnic d cell function. 613 Oct 79

To determine the effectiveness of glucagon suppression in improving glucose homeostasis in diabetes, tracer-determined glucose kinetics were measured during a 6-h somatostatin infusion in six alloxan-diabetic dogs (moderately severe diabetes) and five depancreatized dogs deprived of insulin treatment for 3 days (prolonged severe diabetes). Plasma immunoreactive glucagon (IRG) decreased 70 +/- 9% in the alloxan-diabetic and 80 +/- 4% in the depancreatized dogs. Portal vein levels of plasma immunoreactive insulin (IRI) fell (17.0 +/- 2.3 to 4 micro.5 +/- 0.4 microU/ml) as did peripheral vein IRI levels (6.7 +/- 0.9 to 4.7 +/- 0.5 microU/ml) in the alloxan-diabetic dogs. In the depancreatized dogs plasma IRI levels were undetectable. Plasma glucose concentrations fell (278 +/- 17 to 169 +/- 12 mg/dl) during IRG suppression in the alloxan-diabetic dogs due to a rapid and sustained decrease in glucose production (Ra) (6.0 + 0.9 to 3.6 + 0.3 mg X kg-1 X min-1). Glucose disappearance (Rd) decreased gradually (5.9 + 0.6 to 3.9 + 0.2 mg X kg-1 X min-1). In contrast, in the depancreatized dogs, IRG suppression did not alter glucose concentrations or kinetics. Thus, glucagon suppression decreased glycemia by decreasing Ra only in moderately severe diabetes. However, this was associated with decreased rather than improved glucose utilization. The ineffectiveness of glucagon suppression during prolonged severe diabetes could relate to the degree and duration of the metabolic derangement and/or indicate that the continuous presence of some insulin is necessary for glucagon suppression to improve glucose homeostasis.
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PMID:Glucagon suppression improves glucoregulation in moderate but not chronic severe diabetes. 613 57

The effects of synthetic rat C-peptide 1 and C-peptide 2 on plasma insulin and blood glucose concentrations in the rat were studied. Infusion of rat C-peptide (500 micrograms X h-1 X kg-1) diminished glucose induced increase of plasma insulin by 56% (15.2 +/- 0.9 versus 6.6 +/- 0.6 ng/ml, p less than 0.01, mean +/- SEM). Somatostatin infused at a rate of 50 micrograms X h-1 X kg-1 body weight inhibited glucose-induced insulin secretion by 33%. In the presence of a mixture of both C-peptides or somatostatin, blood glucose after intravenous glucose was higher than in the control experiments. In alloxan-diabetic rats, C-peptide (160 micrograms/kg) significantly increased and prolonged the hypoglycaemic effect of exogenous insulin. It is suggested that C-peptide may not be a biologically inert substance.
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PMID:Effects of synthetic rat C-peptide in normal and diabetic rats. 613 19

The effects of a zinc phosphate suspension of a long-acting, reportedly selective somatostatin analog, Des-Ala1,Gly2 [His4,5,D-Try]-somatostatin (100 micrograms/kg) on postprandial plasma glucose, glucagon, xylose and triglyceride levels were evaluated in alloxan diabetic dogs. Compared to the analog in aqueous solution, the zinc phosphate suspension had a more gradual onset of action in suppressing plasma glucose and xylose levels but a similar onset of action on suppression of plasma triglyceride and glucagon responses. On all these responses, the zinc suspension had a duration of action (greater than 6 hrs) at least three times as long as the aqueous solution. We conclude that such a somatostatin analog in zinc phosphate suspension may have a sufficient duration of action to be useful as an adjunct to insulin in the treatment of diabetes mellitus.
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PMID:Effect of a zinc phosphate suspension of a long-acting somatostatin analog on postprandial plasma glucose, triglyceride and glucagon concentrations in alloxan diabetic dogs. 615 Nov 11

The impact of increased c-AMP levels, short-term fasting as well as experimental diabetes on glibenclamide-induced secretion of somatostatin, insulin and glucagon was studied in the isolated perfused rat pancreas. Dose-response curves revealed that 1 microgram/ml of glibenclamide (in the presence of 3.3 mmol/l of glucose) induced maximal stimulation of insulin and near maximal stimulation of somatostatin release, but did not significantly affect glucagon release. A combination of glibenclamide and the phosphodiesterase inhibitor IBMX synergistically and equally increased both B- and D-cell secretion. Fasting the rats for 24 h significantly suppressed the insulin and glucagon responses to glibenclamide while the concomitant somatostatin response was slightly enhanced. Rats injected with alloxan 3 days prior to perfusion were rendered either moderately diabetic or severely ill with ketoacidosis. Their insulin responses were poor or absent, respectively. In the moderately diabetic rats glibenclamide-induced somatostatin release was blunted while it was abolished in the ketotic rats. The results indicate that glibenclamide-induced B- and D-cell secretion are both modulated by c-AMP, that short-term fasting differentially affects B- and D-cell secretion and that D-cell secretion is inhibited in alloxan diabetes of short duration. It is concluded that the balance of effects by glibenclamide on hormones of the endocrine pancreas may depend on the nutritional and metabolic environment.
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PMID:Modulation by IBMX, fasting and experimental diabetes of glibenclamide-induced islet hormone release from the perfused rat pancreas. 618 48

Abnormalities of somatostatin secretion in diabetes may be secondary to B cell damage with resulting insulinopenia or other effects of diabetogenic agents, including toxicity toward the somatostatin-producing D cells. These possibilities were evaluated in isolated perfused pancreas from normal and alloxan-diabetic rats. In normal rats 3-isobutyl-1-methylxanthine (IBMX, 1 mM), alpha-ketoisocaproic acid (KIC, 5 mM), D-glucose (27 mM), and D-glyceraldehyde (5 mM) stimulated somatostatin release. In diabetic rats 3 days after alloxan, IBMX and KIC elicited somatostatin release, whereas glucose or glyceraldehyde were without effect. In diabetic rats 14 days after alloxan, an otherwise (in normal and 3-day diabetic rats) nonstimulatory concentration of IBMX (0.05 mM) markedly stimulated somatostatin release, whereas as in 3-day diabetic rats glucose was ineffective. Insulin treatment for 2 days did not affect the somatostatin response to glucose in normal rats, did not restore a somatostatin response to glucose 3 days after alloxan, but partially restored (P less than 0.01) a response to glucose (28% of normal) 14 days after alloxan. Insulin in vitro (1 mU/ml, 20 min) failed to restore a glucose effect. Administration of alloxan (1.0 mM) for 5 min to pancreases from normal rats inhibited glucose-induced somatostatin response from 1,562 +/- 401 to 206 +/- 83 pg/15 min (P less than 0.01), whereas the response to IBMX (1 mM) was not significantly decreased. Following different time courses, both an effect of alloxan and of metabolic derangement inhibit somatostatin responses to glucose in alloxan diabetes.
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PMID:Abnormal D cell secretion in alloxan-diabetes: influence by drug and aberrant metabolism. 620 35


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