Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A radioimmunoassay (RIA) method for somatostatin (SRIF) utilizing rabbit antiserum against synthetic SRIF coupled with human serum alpha-globulin is described. Synthetic N alpha-tyrosylated SRIF was labelled with 125I using the lactoperoxidase method and purified on a Sephadex G-10 column. This assay system was highly specific for SRIF and did not cross-react with hypothalamic trophic hormones, pituitary trophic hormones or gastrointestinal hormones. The effect of streptozotocin induced diabetes on the SRIF content was examined in the pancreas, the pancreatic islets, as well as the hypothalamus of rats. SRIF content in both the pancreas and islets of the diabetic rats was shown by RIA to have significantly increased. However, content in the hypothalamus of the diabetic rats did not differ from that of the control. The physiological and pathophysiological significance of the SRIF changes remains to determined.
 ...
PMID:Effect of streptozotocin administration on somatostatin content of pancreas and hypothalamus in rats. 14 51

We describe the characterization of somatostatin-like immunoreactivity (SRIF-LI) found by radioimmunoassay (RIA) to be present in normal human serum. Degradation by serum of 125I-Tyr1 SRIF in the assay, as assessed by chromatoelectrophoresis and immunoprecipitation, was overcome by using EDTA in the assay buffer and Trasylol in the blood samples. Serum samples thus obtained from 48 normal subjects revealed a bimodal distribution of SRIF-LI; 92 per cent (group 1) had a mean level of 0.274 +/- 0.009 ng. per milliliter. What was measured in these sera showed identity to synthetic SRIF on serial dilutions, Sephadex G-25 chromatography, and thin-layer chromatography, and it was shown to be immunoreactive by an antibody-Sepharose affinity system. Higher levels (1.0 +/- 0.041 ng. per milliliter) were found in 8 per cent of the sera; 50 per cent of this material behaved identically as serum SRIF-LI from group 1. The remainder proved to be heterogeneous, consisting of two peaks of large molecular weight, both of which shared immunologic identity with synthetic SRIF as shown by binding to the antibody-Sepharose affinity system. Their further nature is unknown.
Diabetes 1978 May
PMID:The characterization of somatostatin-like immunoreactivity in human serum. 30 57

We examined splanchnic metabolism of alanine in 15 normal males under three sets of conditions: infusion of saline (control studies); infusion of somatostatin (SRIF) (bihormonal deficiency of insulin and glucagon); and infusion of somatostatin plus insulin (selective glucagon deficiency). Net splanchnic alanine uptake (NSAU) remained stable over 2 h during infusion of saline. Infusion of SRIF was associated with a fall in estimated hepatic plasma flow (EHPF) whether or not insulin was infused concomitantly. With SRIF only, arterio-hepatic venous alanine differences increased such that NSAU remained stable over 2 h, despite the fall in EHPF. In contrast, with selective glucagon deficiency, NSAU fell significantly after 2 h, an effect consequent on a fall in EHPF and a delayed fall in arterio-hepatic venous (A-HV) alanine differences. Our studies are compatible with a role for basal glucagon in maintenance of splanchnic extraction of alanine in normal man. However, the SRIF-initiated fall in EHPF may exert an influence on A-HV alanine differences independent of changes in pancreatic hormone secretion.
Diabetes 1979 May
PMID:Splanchnic metabolism of alanine in intact man. Effects of somatostatin and somatostatin plus insulin. 43 78

Seven adult male rats were observed for body weight and microregulation (feeding, drinking, and running patterns) after manipulation of insulin and glucagon levels. They received three injections per day for 3 days each week of 3 U of protamine zinc insulin, .25 mg of zinc glucagon, 50 microgram of protamine zinc somatostatin (SRIF), or protamine zinc vehicle. Diabetes was then induced with an iv injection of streptozotocin (65 mg/kg), and the injection schedule was repeated after the full diabetic syndrome emerged. In all rats whose insulin levels were increased relative to glucagon levels, body weight increased; in those whose glucagon levels were increased relative to insulin levels, body weight decreased. All injections except vehicle reduced meal sizes in both normal and diabetic rats, but only insulin increased the frequency of feeding. These effects could be predicted by the glucostatic theory of food intake regulation and are thus interpreted as supportive of this theory. These results also support the hypothesis that the relative concentration of insulin to glucagon is a regulator of body weight set point.
 ...
PMID:Insulin and glucagon as determinants of body weight set point and microregulation in rats. 68 70

In a group of pancreatectomized subjects, immunoreactive glucagon (IRG) concentrations were normal after an overnight fast, increased after oral glucose, were not suppressed by somatostatin (SRIF) or insulin, and in two of four subjects they rose with an arginine infusion. Even though the SRIF infusion failed to lower IRG, there was a fall in plasma glucose concentration in both subjects. In two subjects, endogenous hyperglycemia occurred during insulin withdrawal without a rise in IRG, and, in one subject, mild diabetic ketoacidosis developed with only a minimal rise in IRG. These results support the presence of an extrapancreatic source of IRG in man. Secretion from these extrapancreatic alpha cells appears to be regulated differently than secretion from pancreatic alpha cells.
Diabetes 1978 Oct
PMID:Immunoreactive glucagon responses to oral glucose, insulin infusion and deprivation, and somatostatin in pancreatectomized man. 70 Feb 56

The effect of exogenously administered somatostatin (SRIF) on meal-stimulated secretions of the exocrine pancreas was studied in dogs with chronic pancreatic fistulas. Dogs were fed 600 gm. of raw meat, and pacreatic output of water, bicarbonate, and protein was measured. Bicarbonate and protein secretions rose markedly postfeeding in all control animals. Four hundred micrograms or 100 mug. of SRIF infused for one hour together with a meal completely prevented the postfeeding rise in pancreatic secretions. SRIF (100 mug./hr.) infused one hour after a meal suppressed pancreatic secretions to basal levels within 30 minutes. Pancreatic secretions rose promptly after discontinuation of SRIF in all dogs. These data indicate (1) SRIF completely prevents pancreatic bicarbonate and enzyme responses when given together with a meal; (2) it completely suppresses already initiated pancreatic responses when given one hour after a meal; (3) 100 mug. of SRIF is as effective as 400 mug. in suppressing the postprandial rise in pancreatic secretions. We conclude that SRIF severely interferes with pancreatic secretions during normal alimentation and that this observation should be considered if SRIF is to be used as a therapeutic agent.
Diabetes 1977 Jan
PMID:Effect of somatostatin on meal-stimulated pancreatic exocrine secretions in dogs. 83 May 67

These studies were designed to elucidate the mechanism of inhibitory action of somatostatin (SRIF) on glucagon (IRG) and insulin (IRI) secretion. Studies were carried out in the unrecirculated isolated rat pancreas perfusion with arginine 19.2 mM and glucose 5.5 mM as stimulus primarily for IRG but also IRI secretion. The effects of excess Ca++ (15.2 mEq./L.) and excess K+ (12.8 mEq./L.) on IRG, IRI, and the SRIF-inhibited pancreas were studied. Ca++ excess in five perfusions strikingly stimulated IRG secretion (+92 per cent) but only stabilized IRI secretion compared with control perfusions. K+ excess (in seven perfusions) markedly inhibited IRG secretion (-39 per cent) while stimulating IRI secretion (+16 per cent). Restoration of normal concentrations of K+ resulted in a rebound of IRG to levels 120 per cent that of controls. SRIF, at concentrations from 0.1-20 ng./ml., produced inhibition of both IRG and IRI. In 11 perfusions, with SRIF at 10 ng./ml., IRG decreased more than IRI (-75.2 per cent IRG and -46.9 per cent IRI). In five perfusions, addition of Ca++ (15.2 mEq./L.) 10 minutes after SRIF was started resulted in a reversal of IRG inhibition to 69.4 per cent and IRI to 73.2 per cent of the arginine controls. The reversal by Ca++ of SRIF effect on IRG was greater at higher concentrations of Ca++, suggesting some form of competition. In four perfusions, excess K+ reversed SRIF-induced IRI inhibition to 79.6 per cent that of controls but had no effect on IRG inhibition. Studies in vitro with isolated islets revealed that SRIF (2 mug./ml.) inhibited 45Ca uptake of islets as did epinephrine (10(-5) M). It was concluded that SRIF-induced inhibition of hormone release appears related to an action on Ca++ uptake.
Diabetes 1976 Nov
PMID:Reversal of somatostatin inhibition of insulin and glucagon secretion. 99 24

The interaction of insulin and glucagon during infusion of somatostatin (SRIF), which suppresses secretion of these hormones, was investigated in normal, postabsorptive, concious dogs. Hepatic glucose output (production) and over-all glucose uptake by the tissues was measured with 3-3H-glucose, administered by a priming injection along with a constant infusion. Infusion of SRIF (1.5-5.0 mug/min) for 90 minutes resulted in a moderate hypoglycemia associated with a decrease in glucose production. In some animals glucose production and plasma glucose levels returned to normal before the end of SRIF infusion. Glucose uptake tended to follow plasma glucose levels. Upon termination of SRIF infusion, glucose production and uptake and plasma glucose increased sharply.
Diabetes 1976 Feb
PMID:Interaction of somatostatin, glucagon, and insulin on hepatic glucose output in the normal dog. 124 72

Exercise in the insulin-deficient diabetic state is characterized by a further increase in elevated circulating glucose and NEFA levels and by excessive counterregulatory hormone levels. The aim of this study was to distinguish the direct glucoregulatory effects of insulinopenia during exercise from the indirect effects that result from the metabolic and hormonal environment that accompanies insulin deficiency. For this purpose, dogs underwent 90 min of treadmill exercise during SRIF infusion with (SRIF + INS, n = 8) or without (SRIF - INS, n = 6) intraportal insulin replacement. Glucagon was not replaced, thus allowing assessment of the direct effect of insulinopenia at the liver independent of the potentiation of glucagon action. Glucose was infused to maintain euglycemia. Hepatic glucose production (Ra); glucose utilization (Rd); and LGlcU, LGlcE, and LGlcO were assessed with tracers ([3H]glucose, [14C]glucose) and arteriovenous differences. With exercise, insulin fell from 66 +/- 6 to 42 +/- 6 pM in the SRIF + INS group, and was undetectable in the SRIF - INS group. Plasma glucose was 6.33 +/- 0.38 and 6.26 +/- 0.30 mM at rest in the SRIF + INS and SRIF - INS groups, respectively, and was unchanged with exercise. Ra rose from 7.5 +/- 2.3 to 16.5 +/- 2.2 mumol.kg-1.min-1 and 9.1 +/- 2.0 to 31.4 +/- 3.9 mumol.kg-1.min-1 with exercise in the SRIF + INS and SRIF - INS groups, whereas Rd rose from 19.5 +/- 2.0 to 46.8 +/- 3.9 mumol.kg-1.min-1 and 15.1 +/- 1.8 to 29.9 +/- 3.3 mumol.kg-1.min-1. LGlcU rose from 36 +/- 9 to 112 +/- 25 mumol/min and 15 +/- 4 to 59 +/- 13 mumol/min and LGlcO rose from 5 +/- 2 to 61 +/- 12 mumol/min and 5 +/- 3 to 32 +/- 9 mumol/min with exercise in the SRIF+INS and SRIF-INS groups, respectively. Arterial levels and limb balances of NEFAs and glycerol were similar in the two groups. In summary, during exercise: 1) marked insulinopenia attenuates the increases in muscle glucose uptake and oxidation by approximately 50%, independent of changes in circulating metabolic substrate levels; 2) substantial increases in muscle glucose uptake and oxidation are, however, still present even in the absence of detectable insulin levels; and 3) insulinopenia facilitates the increase in Ra, independent of the potentiation of basal glucagon action. In conclusion, marked insulinopenia contributes directly to the exacerbation of glucoregulation during exercise in the diabetic state by limiting the rises in glucose uptake and metabolism and by enhancing hepatic glucose production.
Diabetes 1992 Oct
PMID:Impact of insulin deficiency on glucose fluxes and muscle glucose metabolism during exercise. 135 61

G-proteins are important mediators of hormonal inhibition of insulin secretion. To characterize the pertussis toxin-sensitive substrates present in HIT cell membranes, we performed immunoblots with specific antisera and found evidence for the presence of Gi alpha 1, Gi alpha 2, Gi alpha 3, and three forms of Go alpha. We observed that pertussis toxin-sensitive substrates mediate all of the effects of SRIF, and a major portion of the effects of EPI, on insulin secretion from rat islets during static incubations. These results agree with our previously reported studies examining phasic glucose-induced insulin secretion from HIT cells. To ascertain whether inhibition of adenylate cyclase, presumably involving coupling of the catalytic subunit to Gi, may be a common mechanism for both hormones, we studied the effects of 8-bromo-cyclic AMP and found that this agent partially prevented the inhibitory effects of both hormones. We also observed that the inhibitory effects of SRIF and EPI on insulin were nonadditive, that both hormones were additive to nickel chloride during inhibition of insulin release, and that they noncompetitively inhibited glipizide-induced insulin secretion through pertussis toxin-sensitive mechanisms. Together, these results suggest that both hormones exert their effects on insulin secretion at multiple G-protein-regulated sites including adenylate cyclase and sites distal to the glipizide-binding site on the KATP channel.
Diabetes 1992 Nov
PMID:G-proteins and hormonal inhibition of insulin secretion from HIT-T15 cells and isolated rat islets. 138 67


1 2 3 4 5 6 7 Next >>