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

Particulate fractions of myocardium taken from spontaneously hypertensive rats (SHR) contained an adenylate cyclase system that was less responsive than normotensive Wistar Kyoto rats to norepinephrine, isoproterenol (mixed beta-agonist), salbutamol (beta 2-agonist), dobutamine (beta 1-agonist), dopamine, histamine, and glucagon. Addition of 5'-guanylylimidodiphosphate to the SHR myocardial preparation again yielded a lessened sensitivity to all agents except norepinephrine, dopamine, and histamine. Chronic treatment of SHR with clonidine and a high dose of propranolol produced a cardiac enzyme that was insensitive to activation by norepinephrine. Similar treatment with a low dose of propranolol did not alter myocardial responses to norepinephrine.
 ...
PMID:Alterations in myocardial adenylate cyclase in spontaneously hypertensive rats. 4 30

The effects in man of adrenergic blocking agents on plasma insulin, glucagon, growth hormone, and lipid metabolism are reviewed. Whereas basal insulin may be slightly inhibited by beta- and enhanced by alpha-adrenergic blockade, more marked suppression may be achieved under circumstances of high exogenous or endogenous catecholamine stimulation. The relative effects of beta1 or combined beta 1 and beta2 blockers in man are unknown. Glucagon release is probably provoked by beta- and inhibited by alpha-stimulation in man. Muscle glycogenolysis is inhibited by propranolol, and under situations of hepatic glycogen depletion, clinical hypopglycemia may occur. This may also account for the failure of significant hyperglycemia to be observed in short-term experiments on fasting subjects in whom insulin release may be suppressed and glucagon release enhanced. Growth-hormone release is enhanced by beta-adrenergic blockade. Free fatty acid formation in vivo is inhibited by intravenous beta blockade, but the effects of oral administration on triglyceride production and lipoprotein profiles remain uncertain. The inter-relationships between the effects of adrenergic blockade at different sites of hormone and substrate release are unclear but may have important consequences in alteration in carbohydrate tolerance and lipid metabolism. The relative effects of beta-blocking drugs with differing specificity must be determined.
 ...
PMID:The metabolic consequences of adrenergic blockade: a reveiw. 23 94

The levels of beta 1- and beta 3-adrenoreceptor mRNAs in several rat tissues were determined simultaneously with a sensitive nuclease protection assay. The beta 1-receptor gene was expressed to varying degrees in most tissues examined. By contrast, high levels of beta 3-receptor mRNA were only found in brown and white adipose tissues, indicating that beta 3-receptor gene expression is essentially adipose tissue specific. Surgical sympathectomy of interscapular brown adipose tissue increased beta 3-receptor mRNA levels by 2.4-fold, but did not affect beta 1-receptor mRNA levels. Exposure of rats to 4 C, which increases sympathetic nerve stimulation of IBAT, reduced beta 3-receptor mRNA levels in intact tissue but did not affect the denervation-induced increase in beta 3-receptor mRNA. Acute treatment of rats with norepinephrine greatly reduced beta 3 mRNA levels in both white and brown adipose tissues, but did not alter beta 1-receptor mRNA levels. These results indicate that beta 1- and beta 3-receptor mRNAs are differentially regulated and that norepinephrine released from sympathetic nerves is an important inhibitory regulator of beta 3-receptor mRNA levels. Injections of the beta-receptor agonist isoproterenol and the beta 3-receptor agonist BRL 26830 each reduced beta 3-receptor mRNA in brown and white fat, whereas injections of glucagon reduced beta 3-receptor mRNA in brown fat only. These data indicate that while stimulation of beta 3-receptors is sufficient to down-regulate beta 3 mRNA, other receptors that stimulate adenylyl cyclase have the same effect. Finally, the agonist-induced down-regulation of beta 3-receptor mRNA was associated with a reduction in beta 3-receptor activation of adenylyl cyclase in white adipose tissue.
 ...
PMID:Differential adrenergic regulation of beta 1- and beta 3-adrenoreceptor messenger ribonucleic acids in adipose tissues. 130 20

Previous studies have shown that both transforming growth factor beta (TGF-beta) and cyclic AMP (cAMP) inhibit hepatocyte DNA synthesis. While cAMP (in addition to being stimulatory in G0/early G1) exerts its inhibition on hepatocytes late in G1, the point where TGF-beta inhibits has not been precisely defined. We have now examined further the inhibitory effects of cAMP and TGF-beta 1 on DNA synthesis in primary rat hepatocyte cultures and, in particular, tried to determine where in the prereplicative period the cells are sensitive to these agents. Although a transient exposure to TGF-beta 1 (but not glucagon) during the first hours of the cell culturing led to inhibition of DNA synthesis, the cells were more sensitive at a point late in G1, where they also were inhibited by cAMP. Thus, exposure to TGF-beta 1, glucagon, or the cAMP analogue 8-chlorophenylthio-cAMP at a time when there was a continuous recruitment of cells to S phase strongly decreased the rate of S-phase entry. For both TGF-beta 1 and cAMP the inhibition was established within 1-2 h, the lag time being indistinguishable for the two agents. No evidence was found for a synergism between TGF-beta 1 and cAMP. Treatment with TGF-beta 1 did not detectably alter basal or glucagon-stimulated cAMP concentrations. The results suggest that in hepatocytes there is a process immediately before the G1/S border which is sensitive to both TGF-beta 1 and cAMP and which appears to represent a major point of inhibition.
 ...
PMID:Inhibition of hepatocyte DNA synthesis by transforming growth factor beta 1 and cyclic AMP: effect immediately before the G1/S border. 131 26

Evidence suggests that ethanol desensitizes hepatocytes to the trophic effects of hormones. Cyclic AMP-dependent signals are important regulators of intermediary metabolism, cellular proliferation and differentiation, and modulate liver growth during hepatic regeneration. The events leading to cyclic AMP accumulation after partial hepatectomy were characterized in rats consistently fed ethanol-containing diets and compared with results in rats fed isocaloric amounts of nonethanol diet to determine whether altered cyclic AMP-dependent signal transduction contributes to ethanol-associated aberrations in hepatic growth regulation. Ethanol treatment significantly inhibited hepatic accumulation of cyclic AMP after partial hepatectomy. This was most likely the result of decreased synthesis of cyclic AMP because activation of adenylyl cyclase by agents acting through receptors (e.g., glucagon or isoproterenol), GTP-binding proteins (GTP-gamma-S) and directly on adenylyl cyclase (e.g., forskolin) was significantly inhibited in ethanol-fed rats. Both homologous and heterologous desensitization contributed to this effect. beta 1-Adrenergic receptors were relatively down-regulated 6 hr after partial hepatectomy in ethanol-fed rats, whereas glucagon receptor kinetics were similar in the two groups. Liver membrane expression of GTP-binding proteins differed markedly after partial hepatectomy in ethanol-fed and pair-fed rats. Ethanol significantly inhibited post-partial hepatectomy induction of the stimulatory G protein, Gs alpha but led to overexpression of the inhibitory, G(i)2 alpha, subunit. Steady-state messenger RNA levels of these G proteins were similar in ethanol-fed and pair-fed rats, suggesting that ethanol inhibits G protein expression posttranscriptionally.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Chronic ethanol consumption disturbs G-protein expression and inhibits cyclic AMP-dependent signaling in regenerating rat liver. 133 Aug 68

To evaluate the effect of beta 1-blockade (metoprolol) on the plasma glucose thresholds initiating counterregulatory hormone responses and symptoms of hypoglycemia, we used a modified glucose clamp technique to produce a standardized gradual glucose decline from 5.0 to 2.0 mmol/l in nine patients with insulin-dependent diabetes mellitus (IDDM) (HbAlc range 6.7-10.3%, duration of diabetes 5-18 years, autonomous neuropathy present in three of the patients). The responses were studied once with metoprolol and once with placebo, in random order. With the beta 1-selective blockade, epinephrine release was triggered at a significantly higher (p less than 0.02) plasma glucose level (3.5 mmol/l) than it was with placebo (3.0 mmol/l). Metoprolol did not change thresholds for growth hormone (3.7/3.5 mmol/l), cortisol (2.9/2.9 mmol/l), glucagon (2.8/2.8 mmol/l) or for pancreatic polypeptide (2.8/2.7 mmol/l). The peak responses of epinephrine and growth hormone were significantly higher (p less than 0.01) with the beta 1-blockade. Metoprolol did not change the thresholds for neuroglycopenic and autonomic symptoms. Six out of the seven patients who answered yes to having hypoglycemia did so at a higher blood glucose with metoprolol than without. In our study, the beta 1-selective blockade altered the responses of counterregulatory hormones, but it did not change the thresholds for hypoglycemic symptoms.
 ...
PMID:The effect of selective beta 1-blockade on glucose thresholds for release of counterregulatory hormones and symptoms in insulin-dependent diabetes mellitus. 134 50

The beta 3-adrenoceptor agonist, BRL 26830A, which is not inhibited by either beta 1 or beta 2-selective antagonists, has been shown to possess anti-obesity and anti-diabetic actions. However, the effects of this agent on insulin and glucagon release have not yet been substantiated. Therefore, we tested the hypothesis that BRL 26830A promotes insulin and glucagon secretion via beta 3 receptors on pancreatic islet B and A cells. In ICR mice fasted for 48 h, BRL 26830A significantly stimulated insulin secretion from 5 min after administration, markedly decreased blood glucose levels from 30 min after administration, and significantly increased glucagon secretion from 30 min after administration. The administration of a non-selective beta-receptor antagonist, at a dose of 50 mg/kg, 30 min prior to BRL 26830A injection completely abolished the effects induced by BRL 26830A. However, the administration of a beta 1-selective antagonist at doses of 50 or 100 mg/kg did not produce any significant effects. On the action of BRL 26830A, whereas the administration of a beta 2-selective antagonist at 50 mg/kg, a near maximal effective dose, partially abolished the effects of BRL 26830A. BRL 26830A had no effect on insulin, glucagon, or glucose levels in streptozocin (STZ) diabetic mice fasted for 48 h. These results suggest that, in mice, BRL 26830A may promote insulin secretion mainly via beta 3 receptors and partially via beta 2 receptors on pancreatic-islet B cells, and that glucagon may be secreted as the result of hypoglycemia induced by this agent.
 ...
PMID:Effects of a beta 3-adrenoceptor agonist, BRL 26830A, on insulin and glucagon release in mice. 168 48

1. In rat isolated islets of Langerhans the selective beta 2-adrenoceptor agonist, clenbuterol (1 to 20 microM), significantly increased the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) within 2 min of incubation. 2. The cyclic AMP response to clenbuterol was inhibited in the presence of the selective beta 2 adrenoceptor antagonist, ICI 118551 (0.1 or 10 microM) but remained unchanged when the beta 1-antagonist, atenolol (0.1 microM) was administered. 3. Despite causing an elevation in cyclic AMP, clenbuterol (up to 20 microM) failed to influence insulin secretion at any glucose concentration tested, even in the presence of a phosphodiesterase inhibitor. 4. By contrast, clenbuterol elicited a dose-dependent rise in the rate of glucagon secretion; the maximal agonist-induced increase in secretion was two fold, a response equivalent to that observed with 20 mM L-arginine. 5. ICI 118551 significantly inhibited the rise in glucagon secretion induced by clenbuterol (up to 20 microM). 6. The results indicate that the rat islet A cell population is equipped with functional beta 2-adrenoceptors which influence glucagon secretion via the second messenger cyclic AMP, but that the B cells are deficient in functional beta-receptors.
 ...
PMID:Selective stimulation of glucagon secretion by beta 2-adrenoceptors in isolated islets of Langerhans of the rat. 171 26

In heart failure, an increase in the activity of the sympathetic nervous system takes place to maintain perfusion pressure to vital organs, resulting in increased levels of noradrenaline in the blood of these patients. This permanent stimulation produces a down-regulation of cardiac beta-adrenoceptors. Since noradrenaline acts primarily on the cardiac beta 1-adrenoceptor subtype, beta 1-adrenoceptors decrease in number, whereas the beta 2-adrenoceptor subpopulation remains unchanged in most instances. Consequently, the positive inotropic response to beta-adrenoceptor agonists is diminished. However, there is also a decrease in the positive inotropic effect of beta 2-adrenoceptor agonists, histamine and cAMP-phosphodiesterase inhibitors such as milrinone, whereas the positive inotropic effect of cAMP-independent Na(+)-channel activators such as DPI 206-106 and the effects of cardiac glycosides are not diminished. These observations suggest a more generalised alteration of the cAMP-adenylate cyclase system in the failing heart. Stimulatory guanine nucleotide-binding protein (Gs) couples receptors to adenylate cyclase that stimulate cAMP formation, such as beta-adrenoceptors, histamine receptors and glucagon receptors. In the failing human heart, Gs content has been reported to remain unchanged as compared with that in non-failing myocardium. However, there is a 35%-40% increase in inhibitory guanine nucleotide-binding proteins (Gi), which are involved in the receptor-mediated inhibition of adenylate cyclase. Taken together, two defects of the cAMP-adenylate cyclase system have been identified: an increase in Gi content and a decrease in the number of beta-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Alterations of the cAMP-adenylate cyclase system in the failing human heart. Consequences for the therapy with inotropic drugs]. 197 43

The effects of cold exposure (7 days, 5 degrees C) and cold acclimation (21 days, 5 degrees C) on the regulation of lipolysis were investigated in adipocytes isolated from epididymal fat pads of rats. Catecholamines stimulated lipolysis in an affinity sequence typical of the beta 1-adrenoceptor subtype: one-half maximum velocity (1/2 Vmax) isoproterenol (35 nM) much greater than 1/2 Vmax norepinephrine (150 nM) approximately 1/2 Vmax epinephrine (200 nM). Cold exposure markedly decreased the sensitivity (1/2 Vmax) and the responsiveness (Vmax) of the adipocytes to the lipolytic action of catecholamines. Addition of adenosine deaminase to fat cells isolated from cold-exposed rats did not normalize the lipolytic activity, suggesting that extracellular adenosine was not responsible for the obtunded lipolysis. This effect of cold exposure was transient as the lipolytic response to catecholamines was normal in fully cold-acclimated animals. Remarkably, the responsiveness of adipocytes to the lipolytic action of glucagon (200 nM) and adrenocorticotropic hormone (ACTH, 1 microM) progressively increased during cold acclimation. Adipocyte lipolytic response to dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and theophylline was normal in cold-exposed rats, indicating that the lipolytic defect resides at an early step in the lipolytic cascade (pre-cAMP). On the other hand, the antilipolytic effect of insulin on norepinephrine-induced lipolysis significantly decreased during cold acclimation, particularly at physiological levels of insulin (nanomolar level). These results demonstrate that the transient decrease in the lipolytic action of catecholamines observed during cold acclimation is compensated by 1) an increased responsiveness of adipocytes to glucagon and ACTH and 2) by a decreased effectiveness of insulin to induce antilipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alterations in adipocyte response to lipolytic hormones during cold acclimation. 215 29


1 2 3 4 5 Next >>