Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin, or SRIF (Somatotropin Release Inhibiting Factor), is a tetradecapeptide of hypothalamic origin, which inhibits the secretion of growth hormone. It has also been recognized in other parts of the central nervous system, in the islets of Langerhans, and the mucosa of the upper digestive tract. Parenteral administration of synthetic SRIF inhibits the release of growth hormone, basal and stimulated by muscular exercise, arginine, L-DOPA, insulin-induced hypoglycemia, and sleeping. It also inhibits insulin and glucagon secretion, basal and stimulated, and several other secretory processes in endocrine and exocrine glands. It may have a depressor effect on some neurons in the central nervous system. Considerable interest has been prompted in the field of diabetology by the demonstration of somatostatin-induced suppression of growth hormone and glucagon : both hormones are over-secreted in many diabetic patients, and both may be noxious for small blood vessels in the diabetic. The eventual therapeutic use of somatostatin in humans is restricted, for the moment, by the unavaibility of long-acting SRIF preparations and the possibility of some adverse effects mainly affecting hemostasis. Evaluation of the physiological role (s) for this newcomer, and of the eventual pathophysiology of endogenous somatostatin, represent an unexpected and exciting field of neuro-endocrinology.
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PMID:[Somatostatin, a new hormone? (author's transl)]. 79 89

Studies were conducted in newborn lambs to gain insight into the significance and mechanism(s) responsible for the rapid rise in plasma immunoreactive glucagon (IRG) which occurs in human and other newborn species immediately after delivery. Three sets of experiments were conducted: group A, control studies (n = 5) in which delivery into room air was followed 1 hr later by cutting of the umbilical cord and periodic blood sampling for a further hour; group B, studies (n = 5) in which somatostatin (SRIF), a known inhibitor of IRG and insulin (IRI) secretion, was infused int othe fetus for 10 min before, and for 1 hr after delivery and immediate cord cutting; group C, studies (n = 5) in which an identical dose regimen of SRIF was infused into fasting newborn lambs aged 24-72 hr. The doses of SRIF used were several fold higher than those proven to suppres pancreatic hormones secretion in other species. In the control studies, plasma IRG levels remained stable until the cord was cut, after which event levels rose 5-6-fold (59 +/- 15 pg/ml to 305 +/- 98 pg/ml, P less than 0.05). Simultaneously, plasma free fatty acid (FFA) concentrations rose significantly (280 +/- 80 to 780 +/- 100 muEq/liter, P less than 0.05) and IRI remained unchanged. Plasma glucose concentrations, however, in contrast to observations in other species, did not fall, and therefore, hypoglycemia was not the stimulus for the glucagon surge. SRIF infusion at birth (group B) did not prevent the rise in IRG. Again blood glucose values did not fall, but in contrast to the control studies plasma IRI levels rose and the rise in FFA did not occur. Later SRIF infusion (group C) resulted a prompt and sustained suppression of IRG and IRI and a significant fall in blood glucose. These results suggest that an adrenergic mechanism rather than curtailment of nutrients is the major stimulus to the neonatal surge in IRG.
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PMID:Possible mechanisms and significance of the neonatal surge in glucagon secretion: studies in newborn lambs. 87 5

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.
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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.
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PMID:Interaction of somatostatin, glucagon, and insulin on hepatic glucose output in the normal dog. 124 72

The effects of somatostatin-28, somatostatin-14, and a synthetic somatostatin octapeptide analogue, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH2 (cyclo SS-8) were examined on contraction of dispersed gastric smooth muscle cells from guinea pigs. The somatostatins did not cause contraction of gastric smooth muscle cells, nor did they inhibit carbachol-stimulated contraction. However, they reversed vasoactive intestinal peptide (VIP)-induced inhibition (relaxation) of carbachol-stimulated contraction. Somatostatin-28 had a half-maximal effect (EC50) at 1.6 +/- 0.8 nM, cyclo SS-8 at 0.6 +/- 0.3 nM, but somatostatin-14 had no effect even when used in concentrations as high as 1 microM. Incubation of muscle cells with peptidase inhibitors phosphoramidon (1 microM) plus amastatin (10 microM) had no effect on the EC50 of somatostatin-28 or cyclo SS-8 but increased the potency of somatostatin-14 greater than 1,000-fold. When peptides were incubated with muscle cells and the products applied to high-performance liquid chromatography, cyclo SS-8 was not degraded, but somatostatin-14 was rapidly degraded when present alone, and the addition of peptidase inhibitors partially inhibited the degradation. Cyclo SS-8 had its maximal effect at 0.5-1 min and inhibited relaxation induced by VIP, isoproterenol, glucagon, or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Cyclo SS-8 partially inhibited the increase in VIP-stimulated cAMP. Preincubation with pertussis toxin blocked the inhibitory action of cyclo SS-8 on VIP or DBcAMP-induced relaxation. These results indicate that gastric smooth muscle cells rapidly degrade somatostatin-14 and suggest that muscle cell peptidases could have a major effect on the actions of somatostatin-14.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of somatostatins on gastric smooth muscle cells. 134 75

Thirty-eight gestating sows were either immunized against somatostatin (SRIF) and/or injected with growth hormone-releasing factor (GRF). Treatment effects on carcass composition and resistance of newborn piglets to a 60-hour fast were investigated. Protein content of carcasses at birth was increased in piglets of sows receiving GRF or immunized against SRIF, however, when sows received both treatments there was a reduction in carcass protein content (p = 0.01). Other carcass components were unaltered by treatments, and none of the treatments affected metabolic or endocrine profiles of piglets at birth. Concentrations of GH, IGF-I (p less than 0.01), glucagon and cortisol (p less than 0.05) increased linearly with duration of fast, whereas glucose values decreased. Resistance to fasting was unaltered in piglets from any treatment thereby suggesting that exogenous GRF and/or SRIF immunization of sows during gestation are unlikely to improve survival of newborn piglets.
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PMID:Carcass composition and resistance to fasting in neonatal piglets born of sows immunized against somatostatin and/or receiving growth hormone-releasing factor injections during gestation. 134 59

A glucagon infusion algorithm has been developed to reestablish basal glycemia when pancreatic insulin and glucagon secretion are inhibited by somatostatin (SRIF). When insulin alone is infused intraportally during SRIF to replace endogenous hormone release, hypoglycemia is generated by the combined actions of both peptides. In the presence of SRIF infusion, the normal physiologic response to hypoglycemia, i.e. stimulation of glucagon secretion and glucagon-induced increase in hepatic glucose production, has been prevented. Our computer algorithm, "BASREP", was designed to mimic the normal pancreatic counterregulatory response by substituting endogenous alpha-cell secretion with exogenous intraportal infusion. Sequential measurements of glucose concentration are analyzed with a minimal mathematical model of glucose disappearance, adapted to include a variable to describe glucagon stimulation of hepatic glucose production. Based upon the observed change in plasma glucose, BASREP computes after every sample the infusion rate of glucagon necessary to stimulate glucose production and maintain desired glucose level. This method minimizes instabilities and should prove useful in future investigations of glucose metabolism.
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PMID:BASREP: a method for maintaining euglycemia during somatostatin suppression of pancreatic secretion. 135 14

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.
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PMID:Impact of insulin deficiency on glucose fluxes and muscle glucose metabolism during exercise. 135 61

The comparative morphology of the endocrine pancreas was studied in 11 species of lacertids. Four major cell types were identified immunocytochemically in the endocrine pancreas: glucagon-immunoreactive A-cells, insulin-immunoreactive B-cells, somatostatin-(SRIF)-immunoreactive D-cells, and pancreatic polypeptide(PP)-immunoreactive F-cells. Different distributions of the four cell types were seen in the endocrine tissue within the exocrine parenchyma. F-cells were rare or absent in the splenic lobe and abundant in the duodenal lobe, in which they were usually widespread in the exocrine parenchyma and rarer in the islets. The other three cell types were always present in the islets. The central core consisted of B- and A-cells, with B-cells predominating. The peripheral mantle was formed by A-cells and less abundant D-cells. Rare D-cells were also found in the central core. D- and F-cells showed projections often closely associated with capillaries. The observed arrangements in islets and isolated cells may represent an endocrine network that, in addition to systemic actions, may regulate exocrine function in a paracrine fashion.
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PMID:An immunocytochemical study of the endocrine pancreas in three genera of lacertids. 135 81

In order to assess the ability of nicotinic acid to decrease plasma glucose concentration, normal individuals were given continuous four hour infusions of either nicotinic acid (NA), somatostatin (SRIF), NA + SRIF, or 0.9% NaCl (Saline). Plasma non-esterified fatty acid (NEFA) concentration decreased to about one-fourth of the basal value in response to either NA or NA + SRIF, associated with statistically significant decreases in plasma glucose concentration. The ability of NA and NA + SRIF to decrease plasma glucose concentration was seen despite the fact that plasma insulin concentrations also fell significantly during both infusions. Although plasma glucose concentration fell significantly in response to both NA and NA + SRIF, the effect of NA + SRIF was approximately twice as great as that seen with NA alone. The augmented hypoglycaemic effect of NA + SRIF as compared to NA alone was associated with a concomitant fall in plasma glucagon concentration. In contrast, plasma glucose concentration did not change following Saline, and was actually higher than baseline after the infusion of SRIF alone. These results provide evidence that NA can lower plasma glucose concentration in normal volunteers, and suggests that this is mediated by the NA-associated decrease in plasma NEFA concentration.
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PMID:Effect of nicotinic acid on plasma glucose concentration in normal individuals. 135 76


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