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)

Beta-blockade is known to induce muscle fatigue and tendency to hypoglycaemia during prolonged exercise. In addition, beta-blocking agents influence the secretion of many hormones, which regulate glucose. We have investigated the effects of a beta 1-selective (metoprolol) and a non-selective (propranolol) beta-blocking agent on muscle glycogenolysis, blood glucose and lactate levels, plasma levels of free fatty acids and on secretion of insulin, growth hormone, glucagon and cortisol during physical exercise in a double blind cross-over study in seven healthy male volunteers. They participated in three bicycle ergometer tests each lasting for 30 minutes under treatment of placebo (C), metoprolol (M) or propranolol (P). A biopsy was obtained from the vastus lateralis muscle before and immediately after the exercise for muscle glycogen assay. The glycogen concentration after exercise tended to be lower in C than in M or P experiment. The blood glucose level decreased during P and at 30 min there was a significant difference between P and C. The blood lactate was significantly lower before exercise during P than C or M. The increase of blood lactate during exercise, however, was not inhibited by P. Both beta-blocking agents counteracted the increase of FFA during exercise. There was a marked increase of growth hormone secretion during beta-blockade. The secretion of glucagon and cortisol were slightly increased by P and M, but the plasma insulin level was not affected by beta-blockade.
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PMID:Modification of the metabolic and hormonal response to physical exercise by beta-blocking agents. 675 73

Recovery from acute hypoglycaemia induced by the injection of insulin has been examined in six human subjects under control conditions, under non-selective beta blockade (propranolol) and under selective beta 1 blockade (metoprolol). The normal blood glucose recovery was biphasic with an initial rapid and a slower subsequent phase of recovery. The early recovery mechanism was unaffected by either form of beta blockade, but with propranolol the late phase of recovery was significantly prolonged. Rises in blood lactate and plasma free fatty acids following hypoglycaemia were markedly reduced by propranolol but to a much lesser degree with metoprolol. The counterregulatory hormonal responses of glucagon, cortisol and growth hormone were augmented appropriately for the prolonged hypoglycaemia associated with propranolol. Non-selective beta adrenergic blockade with propranolol is associated with an impairment of the late phase of blood glucose recovery from hypoglycaemia. The possible mechanisms of this impairment are discussed.
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PMID:Hormonal and substrate responses during recovery from hypoglycaemia in man during beta 1-selective and non-selective beta-adrenergic blockade. 679 44

The hemodynamic, hormonal and electrolyte effects of prenalterol, a synthetic selective beta 1 agonist, were studied in six patients with New York Heart Association functional class II and III heart failure. Prenalterol was infused incrementally at 60, 120 and 240 nmol/min, each rate for 24 hours, producing steady-state plasma prenalterol levels of 52 +/- 3, 121 +/- 6 and 194 +/- 9 nmol/1, respectively (mean +/- SEM). Hemodynamic and hormonal measurements were performed before, during and after prenalterol administration under conditions of constant body posture and a regulated intake of dietary sodium and potassium. Prenalterol induced a statistically significant increase in cardiac index (from 2.6 +/- 0.2 to 3.1 +/- 0.3 1/min/m2), with parallel increases in stroke index (from 28 +/- 2 to 34 +/- 2 ml/beat/m2). Forearm blood flow measurements increased (from 2.9 +/- 0.5 to 4.1 +/- 0.6 ml/min/100 g), while calculated systemic vascular resistance fell, as did pulmonary capillary wedge pressure (from 13.7 +/- 1.6 to 10.5 +/- 1.7 mm Hg). The drug did not alter heart rate, arterial pressure, right heart pressures or the frequency of ventricular premature beats. Prenalterol increased plasma renin activity (from 2.9 +/- 0.8 to 6.6 +/- 1.8 nmol/1/hour), angiotensin II (from 59 +/- 12 to 89 +/- 22 pmol/1), urinary aldosterone excretion (from 41 +/- 10 to 78 +/- 34 nmol/day) and plasma insulin (from 10.6 +/- 2.2 to 19.8 +/- 3.9 mU/1). Circulating catecholamines, cortisol, glucose, glucagon or pancreatic polypeptide did not change. Dose-response studies in five patients showed dose-dependent increments in hemodynamic variables, while hormonal changes plateaued at the second dose level. We conclude that prenalterol infusion augments myocardial contractility, reduces systemic vascular resistance, and stimulates insulin release and the renin-angiotensin-aldosterone system.
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PMID:Hemodynamic, hormonal and electrolyte responses to prenalterol infusion in heart failure. 682 3

Rat islets respond to glucose stimulation with a marked first and second phase increase in insulin secretion. In contrast, mouse islets have a similar first phase response but little second phase secretion. In these studies, we determined if activation of phospholipase C (PLC) accounts for these differences in second phase insulin secretion in these two species. Stimulation of freshly isolated mouse and rat islets with 15 mM glucose resulted in comparable first phase insulin secretion; however, the second phase response from mouse islets was only doubled from 28 +/- 6 to 60 +/- 7 pg/islet.min compared with an increase from 24 +/- 4 to 1064 +/- 93 pg/islet.min from rat islets. The addition of the muscarinic agonist carbachol (100 microM) in the presence of 15 mM glucose, however, markedly increased second phase insulin release from mouse islets to 801 +/- 80 pg/islet.min. Similar increases in second phase insulin release from mouse islets were obtained with the addition of 500 nM of the protein kinase C activator tetradecanoyl phorbol acetate in the presence of 15 mM glucose. However, the incretin factor glucagon-like peptide-1, which elevates islet cAMP levels, had little effect on second phase insulin release in the mouse. An analysis of PLC-mediated phosphoinositide (PI) hydrolysis revealed that 15 mM glucose increased inositol phosphate (IP) accumulation 0.5-fold above baseline in mouse islets compared with 3.7-fold in rat islets. In contrast, carbachol stimulated IP accumulation 3.5-fold in both mouse and rat islets. Analysis of PLC isozymes with isozyme specific monoclonal antibodies, demonstrated that mouse islets express 14 +/- 4% of PLC-delta 1 and 18 +/- 6% of PLC-beta 1 compared with rat islets but similar amounts of the PLC-gamma 1 (117 +/- 16%). These findings suggest that the decreased second phase insulin secretory response in mouse compared with rat islets results, at least in part, from an inability of high glucose to stimulate comparable increments in PI hydrolysis. This lack of glucose responsiveness may be due to the pronounced underexpression of specific PLC isozymes in the mouse.
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PMID:Regulation of insulin release by phospholipase C activation in mouse islets: differential effects of glucose and neurohumoral stimulation. 758 23

In hepatocytes, glucocorticoids control the expression of several genes and exert significant, but complex, regulation of the proliferation. To shed more light on the growth responses to glucocorticoids in these cells, we treated adult rat hepatocytes in primary culture with dexamethasone, in various combinations with other hormones (insulin, glucagon, transforming growth factor beta 1 (TGF beta 1)), and examined the relationship between the effects on the DNA synthesis and the mRNA level of phosphoenolpyruvate carboxykinase, a gene typically expressed in differentiated hepatocytes. Insulin exhibited the previously observed suppressing effect on the glucocorticoid-induced phosphoenolpyruvate carboxykinase mRNA level, and also reversed growth-inhibitory effects of the glucocorticoid. Dexamethasone and glucagon (via cAMP) acted strongly synergistically both in enhancing the phosphoenolpyruvate carboxykinase expression and inhibiting the growth, the inhibitory effect of glucagon on DNA synthesis being totally dependent on dexamethasone. The effects of dexamethasone plus glucagon on both the phosphoenolpyruvate carboxykinase mRNA abundance and the DNA synthesis were partially counteracted by insulin. Dexamethasone is permissive for a promoting effect of TGF beta 1 on phosphoenolpyruvate carboxykinase expression, and was found to increase the maximal inhibitory effect of (but reduced the sensitivity to) TGF beta 1 on the DNA synthesis. The results indicate that there is an inverse glucocorticoid-induced regulation of the DNA synthesis and the expression of a liver-typical gene.
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PMID:Dexamethasone inversely regulates DNA synthesis and phosphoenolpyruvate carboxykinase mRNA levels in cultured rat hepatocytes: interactions with insulin, glucagon, and transforming growth factor beta 1. 761 40

Hepatocyte-nuclear factor 3 beta (HNF-3 beta), a member of the HNF-3 gene family, is expressed in glucagon-producing islet cells and represses glucagon gene expression. We show here that at least three different HNF-3 beta transcripts that encode HNF-3 beta protein variants are present in glucagon-producing cells, HNF-3 beta 1, HNF-3 beta 2, and HNF-3 beta 3. Compared with the HNF-3 beta 1 cDNA, HNF-3 beta 2 cDNA lacks sequences of exon 1 while exons 1 and 4 are absent from the HNF-3 beta 3 cDNA. The deduced amino-acid (aa) sequence of HNF-3 beta 2 and HNF-3 beta 3 proteins differs from HNF-3 beta 1 by a 6-aa amino-terminal extension and by the absence of the first 30 aa, respectively. HNF-3 beta 1, HNF-3 beta 2, and HNF-3 beta 3 bind to the major enhancer of the rat glucagon gene G2 with similar affinity. By contrast to HNF-3 beta 1, which represses glucagon gene expression when overexpressed in the glucagon-producing cell line InR1G9, HNF-3 beta 2 and HNF-3 beta 3 do not affect transcriptional activity. Furthermore, cotransfection of HNF-3 beta 2 or HNF-3 beta 3 along with HNF-3 beta 1 decreases the negative effects of HNF-3 beta 1. We conclude that glucagon gene expression may be regulated by the relative abundance of the three different HNF-3 beta variants in alpha-cells.
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PMID:Hepatocyte-nuclear factor 3 beta gene transcripts generate protein isoforms with different transactivation properties on the glucagon gene. 777 82

Transforming growth factor beta 1 (TGF beta 1) elevated the phosphoenolpyruvate carboxykinase (PEPCK) mRNA abundance in primary cultures of rat hepatocytes. Although this increase was not as large as the rise in PEPCK gene expression induced by the cAMP-elevating agents glucagon or isoproterenol, the effect of TGF beta 1 was several-fold and concentration-dependent, with ED50 at about 2.5 pM, which is in the same concentration range as the previously found growth-inhibitory effect of TGF beta. The data show that the level of mRNA for PEPCK, an enzyme typically expressed in the liver, can be regulated in the same direction by TGF beta 1 and cAMP.
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PMID:Transforming growth factor beta 1 increases the phosphoenolpyruvate carboxykinase mRNA level in cultured rat hepatocytes. 801 91

Na,K-ATPase activity and isoform expression were measured in rat small intestinal mucosa taken from both normal and streptozocin-treated diabetic rats. Enzyme activity and abundance was 1.7-2.3-fold higher in rats diabetic for 2 wk than in controls. This was associated with 1.4-1.7-fold increases in small intestinal protein and DNA content. Ouabain inhibition curves of Na,K-ATPase were monophasic with Kis of 2.6 +/- 1.4 x 10(-4) and 2.0 +/- 1.2 x 10(-4) M for control and diabetic rats, respectively (NS). Northern blot analysis revealed a 2.5-fold increase in mRNA alpha 1 and a 3.4-fold increase in mRNA beta 1 in diabetic rats relative to controls. Two thirds of this increase occurred within 24h after injection of streptozocin. Immunoblots of intestinal enzyme preparations from diabetic and control rats indicated the presence of alpha 1 and beta 1 subunits but not of alpha 2 or alpha 3. Administration of glucagon (80 micrograms/kg) to normal rats daily for 14-16 d increased mRNA alpha 1 3.1-fold but did not increase mRNA beta 1 or enzyme activity. In experimental diabetes, alpha 1 and beta 1 isoforms of Na,K-ATPase are coordinately upregulated at both protein and mRNA levels, an effect which appears to be partially mediated by the associated hyperglucagonemia.
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PMID:Na,K-ATPase in diabetic rat small intestine. Changes at protein and mRNA levels and role of glucagon. 820 Oct 10

We have previously described the use of a chemically defined medium (CDM) supplemented with epidermal growth factor (EGF) and dimethylsulfoxide (DMSO) to maintain long-term cultures of rat hepatocytes in a highly differentiated state. In this study, conditions necessary to stimulate high levels of DNA synthesis in hepatocytes in long-term DMSO culture were defined. Hepatocytes were maintained in culture for 20 days in CDM containing DMSO and EGF, insulin, and glucagon. EGF, insulin, and glucagon were then removed for 7 days. Readdition of EGF, insulin, and glucagon at day 27 (shiftup) was accompanied by a three- to sixfold increase in labeling index. If DMSO or dexamethasone (dex) + DMSO were removed at time of shiftup, the labeling index increased by 18- to 54-fold. TGF beta inhibited DNA synthesis stimulated by EGF shiftup, TGF alpha shiftup, or EGF shiftup in combination with removal of dex + DMSO. Stimulation of DNA synthesis was accompanied by a specific, sequential induction of protooncogene mRNA levels; c-fos mRNA was induced 23-fold at 0.5 h after readdition of EGF; c-myc mRNA was induced three- to four-fold by 0.5 h; TGF alpha mRNA was induced sevenfold by 8 h; K-ras mRNA was induced fourfold by 26 h. Changes in protooncogene expression paralleled changes seen in regenerating liver. When DMSO was removed for greater than 48 h, the cells flattened and spread out, chords of cells were no longer well defined, albumin mRNA levels decreased, and fibronectin, beta 1 integrin, and TGF beta transcripts increased.
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PMID:Stimulation of DNA synthesis and protooncogene expression in primary rat hepatocytes in long-term DMSO culture. 843 3

1. Respiratory and cardiovascular failure are principle toxic effects of beta-blocker overdose. Respiratory arrest is the primary cause of death in beta-blocker intoxicated rats. 2. The effect of beta-adrenoceptor agonists on respiratory and cardiovascular failure in beta-blocker overdose was investigated in a model of acute d,l-propranolol (30 mg kg-1 h-1) intoxication in spontaneously breathing rats. 3. Neither the aselective, hydrophilic beta-agonist isoprenaline (10, 25, 50 micrograms kg-1 min-1), nor the beta 1-selective, lipophilic beta-agonist flerobuterol (1, 3, 10 microgram kg-1 min-1) and the beta 2-selective, lipophilic beta-agonist clenbuterol (10, 25, 50 micrograms kg-1 min-1) had any beneficial effect on cardiovascular and respiratory variables or survival time in d,l-propranolol intoxicated spontaneously breathing rats. 4. Isoprenaline (10 micrograms kg-1 min-1) had no favourable effect on haemodynamic and respiratory variables in artificially ventilated d,l-propranolol intoxicated rats either. 5. Addition of dopamine to isoprenaline resulted in a significant reduction of survival time, primarily caused by a decreased in mean arterial blood pressure, in artificially ventilated d,l-propranolol intoxicated rats. Addition of glucagon to isoprenaline did not affect survival time. 6. Artificial ventilation is the most important supportive measure in d,l-propranolol intoxication in the rat.
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PMID:Reduced survival after isoprenaline/dopamine in d,l-propranolol intoxicated rats. 864 2


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