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)

Previous investigations in our laboratory revealed subsensitivity of right ventricular tissue, isolated from one month STZ-diabetic rats, to the inotropic effects of isoproterenol. The present study was concerned with the characterization of this subsensitivity phenomenon. Observations of supersensitivity to methoxamine accompanied by decreased responsiveness to glucagon without a change in responsiveness to forskolin suggested a specific effect of diabetes on pathways involving receptor-mediated activation of adenylate cyclase. Radioligand binding analysis further revealed a specific decrease in the population of the high affinity state of the beta-adrenoceptor. Since the high affinity receptor state is a necessary intermediate for adenylate cyclase activation and enhanced myocardial contractility, it is proposed that the specific decrease in the high affinity population of the beta-adrenoceptor contributes to myocardial subsensitivity to isoproterenol observed in the diabetic animals. It is further proposed that the decrease in receptor population is related to increases in circulating epinephrine levels which were evident in the diabetic animals.
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PMID:Alterations in the myocardial beta-adrenoceptor system of streptozotocin-diabetic rats. 303 70

The effect of physical training on glucose, insulin, and glucagon response to epinephrine was assessed in normal and diabetic rats. Male Wistar rats were injected with streptozocin (STZ, 45 mg/kg) and those presenting 1 wk later a blood glucose value between 250 and 400 mg/dl were retained in the protocol and randomly assigned to a sedentary or trained group. Similar studies were conducted in control animals. Physical training was done on a treadmill according to a 10-wk program. Epinephrine (0.75 microgram/kg/min) was infused intravenously (i.v.) in previously cannulated rats for 1 h and arterial blood samples obtained at 15-min intervals for glucose, insulin, and glucagon measurements. Pancreatic insulin and glucagon content was also determined. Basal glucose levels were significantly lower in trained than in sedentary diabetic rats (P less than 0.01). The hyperglycemic response to epinephrine was diminished by 19% and 23% in trained control and diabetic animals, respectively, with a faster return to baseline after stopping epinephrine infusion in both trained groups. Although in nondiabetic rats this could be related to some diminution in the suppressive effect of epinephrine on insulin secretion, this was not the case in diabetic animals. Moreover, while training did not modify epinephrine-induced glucagon response in control rats, the twofold greater (P less than 0.01) glucagon response observed in sedentary diabetic rats was restored to normal in trained diabetic rats. After stopping epinephrine infusion, glucagon levels dropped below the baseline in both groups of trained rats but not in their sedentary counterparts. These effects of training on glucagon response could not be explained by changes in pancreatic glucagon content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diminished glucagon response to epinephrine in physically trained diabetic rats. 390 62

To clarify whether the reactivity of A cells is regulated by B cell function in the pancreas, plasma glucagon (IRG) responses to insulin-induced hypoglycemia and to arginine infusion were evaluated in streptozotocin (STZ; total 40 mg/kg) treated and control dogs. There was no significant rise in plasma IRG levels during the insulin-induced hypoglycemia in the STZ-treated dogs. In contrast, arginine enhanced the IRG secretion from the pancreas to a similar extent in the two groups. This was deduced from the difference between IRG levels in the pancreaticoduodenal and peripheral veins. Neither intravenous glucose nor arginine infusion resulted in a significant rise in plasma insulin (IRI) levels in the STZ-treated dogs. IRI content in the pancreas of STZ-treated dogs was significantly reduced to 5 percent below the levels in the control dogs. The IRG content for control and STZ-treated dogs did not differ. These results indicate that while the responsiveness of A cells to hypoglycemia may depend on the secretory capacity of B cells, such is not the case with arginine.
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PMID:Glucagon secretory responses to insulin-induced hypoglycemia and arginine in streptozotocin-induced diabetic dogs. 636 6

The effects of adrenergic blockers on the glucagon response to insulin hypoglycemia were investigated in diabetic (10-15 days poststreptozocin [STZ] injection) and age-matched control rats. alpha-(Phentolamine nonspecific but predominantly alpha 1), alpha 2-(yohimbine), or beta-(propranolol) adrenergic blockers alone or in combination did not affect plasma glucose levels or plasma glucagon concentrations, in the basal state, in either control or diabetic rats. None of these adrenergic blockers, alone or in combination, inhibited the glucagon response to insulin hypoglycemia in control or diabetic rats. On the contrary, in control rats, the beta-adrenergic blocker alone or in combination with an alpha-adrenergic blocker and in diabetic rats, the alpha-adrenergic blocker alone significantly stimulated the glucagon response to insulin hypoglycemia. Second, the effects of yohimbine on the glucagon response to epinephrine infusion were studied in both young and old rats. Recently, Cherksey et al. (Proc. Soc. Exp. Biol. Med. 1982; 171:196-200) have reported that the adrenergic receptors on rat pancreatic islet cells are of the alpha 2-subtype. Yohimbine (alpha 2-adrenergic blocker) completely blocked the glucagon response to epinephrine infusion in both young and old rats, but had no inhibitory effect on the glucagon response to insulin hypoglycemia in control and short-term diabetic rats. From these observations, it could be inferred that the lack of glucagon response to insulin hypoglycemia in long-term diabetic rats is unlikely to be explained by an impairment of an adrenergic function.
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PMID:Role of sympathetic nervous system in glucagon response to insulin hypoglycemia in normal and diabetic rats. 638 31

The role of glucagon in diabetic hyperglycaemia has been a matter of controversy because of difficulties in the production of selective glucagon deficiency. We developed a high-capacity (40 nmol/ml), high-affinity (0.6 x 10(11) l/mol) monoclonal glucagon antibody (Glu-mAb) and gave i.v. injections (4 ml/kg) to rats in order to study the effect of selective glucagon deficiency on blood glucose. Controls received a mAb against trinitrophenyl. Glu-mAb completely abolished the hyperglycaemic effect of 2.86 nmol/kg glucagon in normal rats (p < 0.05, n = 6). In moderately hyperglycaemic rats injected with streptozotocin as neonates (N-STZ), Glu-mAb abolished a postprandial increase in blood glucose (from 11.2 +/- 0.7 mmol/l to 17.3 +/- 1.8 mmol/l in controls vs 10.5 +/- 0.9 mmol/l to 9.3 +/- 1.0 mmol/l; cross-over: n = 6, p < 0.05). No significant effect of Glu-mAb treatment was observed in more hyperglycaemic N-STZ rats (cross-over, n = 4) and in severely hyperglycaemic rats injected with STZ as adults (n = 6), but after insulin treatment of the latter, at doses partially restoring blood glucose levels (12.7 +/- 4.3 mmol/l), Glu-mAb administration almost normalized blood glucose (maximal difference: 6.0 +/- 3.8 mmol/l; cross-over: n = 5, p < 0.05). In conclusion, our results provide strong additional evidence for the hypothesis that glucagon is involved in the pathogenesis of diabetes. The hormone plays an important role in the development of STZ-diabetic hyperglycaemia, but glucagon neutralization only leads to normoglycaemia in the presence of insulin.
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PMID:Immunoneutralization of endogenous glucagon with monoclonal glucagon antibody normalizes hyperglycaemia in moderately streptozotocin-diabetic rats. 785 93

Insulin secretion is known to be inhibited by alpha 2-adrenergic agonism and stimulated by beta-adrenergic agonism in both experimental animals and humans. In contrast, adrenergic regulation of glucagon secretion remains controversial. This study was designed to determine the effects of alpha 2- and beta-adrenergic agonism on islet alpha cells, using isolated perfused pancreata of normal and streptozocin-induced diabetic (STZ-D) rats. The alpha 2-adrenoceptor agonist clonidine at a concentration of 10(-7) mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (1,286 +/- 90 v 417 +/- 53 ng/L, P < .01) and STZ-D rats (551 +/- 86 v 130 +/- 19 ng/L, P < .01). Also, the beta-adrenoceptor agonist isoproterenol at a concentration of 10(-7) mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (751 +/- 130 v 347 +/- 41 ng/L, P < .05) and STZ-D rats (182 +/- 22 v 92 +/- 20 ng/L, P < .01). Furthermore, these alpha 2- and beta-agonistic effects were almost completely inhibited in the presence of the alpha 2-adrenoceptor antagonist yohimbine and the beta-adrenoceptor antagonist propranolol at a concentration of 10(-6) mol/L, respectively. Insulin secretion was markedly reduced in STZ-D rats. These results suggest that even in a severely diabetic state, not only beta- but also also alpha 2-adrenergic agonism stimulates glucagon secretion from rat pancreatic alpha cells.
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PMID:Effects of alpha 2- and beta-adrenergic agonism on glucagon secretion from perfused pancreata of normal and streptozocin-induced diabetic rats. 810 94

MDL 29311, an analogue of probucol, administered to rats as a 1% dietary admixture for 2 wk before and 5 days after intravenous injection of 40 mg/kg of ALX significantly (P < 0.05) reduced plasma glucose (6.9 +/- 0.3 vs. 19.2 +/- 1.3 mM) and serum triglyceride (0.17 +/- 0.01 vs. 1.82 +/- 0.39 mM) levels in overnight-fasted ALX-plus-MDL 29311-administered rats vs. ALX-administered rats. A cross-over study indicated that MDL 29311 did not attenuate the diabetogenic action of ALX, but rather, directly lowered glucose and triglycerides. In rats injected intravenously with 45, 65, or 85 mg/kg of STZ and then administered control or MDL 29311 diet for 7 days, MDL 29311 decreased fasted plasma glucose to nondiabetic levels, decreased fasted and nonfasted plasma triglycerides by 49-79%, but did not affect plasma insulin levels. In STZ-induced (65 mg/kg) diabetic rats, MDL 29311 attenuated the increase in plasma nonesterified fatty acids during an 18-h fast; had little or no effect on glucagon, pyruvate, lactate, beta-hydroxybutyrate, acetoacetate, or cholesterol; and did not induce hypoglycemia in rats fasted up to 64 h. In nonfasted hyperinsulinemic db/db mice treated for 10 wk, MDL 29311 significantly lowered glucose levels by 14-40%, triglyceride levels by 31-63% and GHb from 8.0 to 5.4%, and had no consistent effect on plasma insulin levels. Because of its marked glucose- and lipid-lowering activity in both nonfasted hyperinsulinemic and fasted insulinopenic animals, MDL 29311 merits additional investigation as a potential antidiabetic agent.
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PMID:MDL 29311. Antioxidant with marked lipid- and glucose-lowering activity in diabetic rats and mice. 832 50

The specific effect of hyperglycemia on the reported decrease in liver glycogen synthase phosphatase activity was studied in STZ-induced diabetic rats with normal fasting insulinemia. Four groups of animals were investigated: control (nondiabetic), diabetic hyperglycemic (STZ), diabetic normoglycemic (STZ followed by 3-day phloridzin treatment), and a diabetic normoglycemic group injected with glucose to reinstate hyperglycemia. None of the treatments significantly altered fasting plasma insulin and glucagon concentrations. We found that hepatic synthase phosphatase activity decreased in STZ-induced diabetic rats and was further markedly reduced when glycemia was normalized in the diabetic animals. This additional decrease in phosphatase activity was almost fully reversed when hyperglycemia was restored by acute glucose infusion of the normoglycemic diabetic rats. In parallel, the levels of liver G6P and F6P were markedly reduced in the diabetic normoglycemic rats and restored with reinstatement of hyperglycemia. In contrast, liver microsomal glucose-6-phosphatase activity was enhanced and glucokinase activity was lowered in all diabetic groups, regardless of glycemia. Our results indicate that hyperglycemia per se counteracts part of the loss of hepatic synthase phosphatase in diabetic animals and provokes the stable conversion of synthase phosphatase from a less active to a more active form.
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PMID:Opposite effects of hyperglycemia and insulin deficiency on liver glycogen synthase phosphatase activity in the diabetic rat. 838 Oct 96

Vanadium salts exhibit a wide variety of insulinomimetic effects. In the present studies, we have examined the modulation of G-protein levels and adenylyl cyclase activity in the liver of streptozotocin-induced chronic diabetic rats (STZD) by vanadyl sulfate treatment and compared it with that of insulin. The basal enzyme activity, as well as the stimulatory effects of guanine nucleotides, glucagon, N-Ethylcarboxamideadenosine (NECA), isoproterenol, forskolin and sodium fluoride (NaF) on adenylyl cyclase were significantly increased in STZ-D rat liver as compared to control. In addition, the levels of stimulatory (Gs alpha) as well as inhibitory (Gi alpha-2 and Gi alpha-3) as determined by immunoblotting techniques were also significantly higher in the STZ-D rat liver, however, the inhibitory effects of oxotremorine and low concentrations of GTP gamma S on adenylyl cyclase were not different in the two groups. Vanadyl sulfate and insulin treatments restored the augmented basal enzyme activity, the stimulations exerted by stimulatory inputs on adenylyl cyclase and the G-protein levels to various degrees, however, vanadyl sulfate was more effective than insulin. In addition, unlike vanadyl sulfate, insulin was unable to improve the stimulation exerted by glucagon and isoproterenol on adenylyl cyclase activity in STZD rats. These results suggest that vanadyl sulfate mimics the effects of insulin to restore the defective levels of G-proteins and adenylyl cyclase activity. From these results it may be suggested that one of the mechanisms by which vanadyl sulfate improves the glucose homeostasis in STZ-D rats may be through its ability to modulate the levels of G-proteins and adenylyl cyclase signal transduction system.
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PMID:Reversal of defective G-proteins and adenylyl cyclase/cAMP signal transduction in diabetic rats by vanadyl sulphate therapy. 892 25

The effects of glucagon-like peptide-1(7-36)-amide (GLP-1) on cAMP content and insulin release were studied in islets isolated from diabetic rats (n0-STZ model) which exhibited impaired glucose-induced insulin release. We first examined the possibility of re-activating the insulin response to glucose in the beta-cells of the diabetic rats using GLP-1 in vitro. In static incubation experiments, GLP-1 amplified cAMP accumulation (by 170%) and glucose-induced insulin release (by 140%) in the diabetic islets to the same extent as in control islets. Using a perifusion procedure, GLP-1 amplified the insulin response to 16.7 mM glucose by diabetic islets and generated a clear biphasic pattern of insulin release. The incremental insulin response to glucose in the presence of GLP-1, although lower than corresponding control values (1.56 +/- 0.37 and 4.53 +/- 0.60 pg/min per ng islet DNA in diabetic and control islets respectively), became similar to that of control islets exposed to 16.7 mM glucose alone (1.09 +/- 0.15 pg/min per ng islet DNA). Since in vitro GLP-1 was found to exert positive effects on the glucose competence of the residual beta-cells in the n0-STZ model. we investigated the therapeutic effect of in vivo GLP-1 administration on glucose tolerance and glucose-induced insulin release by n0-STZ rats. An infusion of GLP-1 (10 ng/min per kg; i.v.) in n0-STZ rats enhanced significantly (P < 0.01) basal plasma insulin levels, and, when combined with an i.v. glucose tolerance and insulin secretion test, it was found to improve (P < 0.05) glucose tolerance and the insulinogenic index, as compared with the respective values of these parameters before GLP-1 treatment.
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PMID:Glucagon-like peptide-1(7-36)-amide confers glucose sensitivity to previously glucose-incompetent beta-cells in diabetic rats: in vivo and in vitro studies. 941 71


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