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)

The humoral modulation of resting muscle heat production of chickens (Gallus domesticus) was investigated in vitro. The resting distal lower limb was perfused via the popliteal artery at 25 degrees C without erythrocytes at constant flow. The preparation was stable for at least 3 hr, showing a constant oxygen uptake (MO2) and perfusion pressure as well as adequately maintaining muscle energy charge and creatine phosphate: creatine ratio. Noradrenaline (NOR), adrenaline (ADR) and serotonin (5-HT) each caused a dose-dependent rise in perfusion pressure. NOR and ADR evoked increased MO2 at low doses eventually followed by decreased MO2 at higher agonist concentrations. 5-HT gave smaller but qualitatively similar MO2 effects. The actions of 50 nM NOR were blocked by prazosin (10 microM) and nitroprusside (0.5 mM), but not altered by propranolol (10 microM). NOR-induced stimulatory MO2 changes in the presence of pharmacological concentrations (1 microM) of glucagon were more pronounced and the thermogenic concentration range of NOR was increased. Taken together, these in vitro findings demonstrate a potential for vasoconstrictor-controlled muscle nonshivering thermogenesis in birds as in marsupials and mammals, suggesting that vascular control of muscle MO2 may be a widespread biological mechanism. The possible implications of these findings for avian nonshivering thermogenesis are discussed.
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PMID:Potential for non-shivering thermogenesis in perfused chicken (Gallus domesticus) muscle. 921 57

1. Exposure to altitude hypoxia elicits changes in glucose homeostasis with increases in glucose and insulin concentrations within the first few days at altitude. Both increased and unchanged hepatic glucose production (HGP) have previously been reported in response to acute altitude hypoxia. Insulin action on glucose uptake has never been investigated during altitude hypoxia. 2. In eight healthy, sea level resident men (27 +/- 1 years (mean +/- S.E.M); weight, 72 +/- 2 kg; height, 182 +/- 2 cm) hyperinsulinaemic (50 mU min-1 m-2), euglycaemic clamps were carried out at sea level, and subsequently on days 2 and 7 after a rapid passive ascent to an altitude of 4559 m. 3. Acute mountain sickness scores increased in the first days of altitude exposure, with a peak on day 2. Basal HGP did not change with the transition from sea level (2.2 +/- 0.2 mg min-1 kg-1) to altitude (2.0 +/- 0.1 and 2.1 +/- 0.2 mg min-1 kg-1, days 2 and 7, respectively). Insulin-stimulated glucose uptake rate was halved on day two compared with sea level (4.5 +/- 0.6 and 9.8 +/- 1.1 mg min-1 kg-1, respectively; P < 0.05), and was partly restored on day 7 (7.4 +/- 1.4 mg min-1 kg-1; P < 0.05 vs. day two and sea level). Concentrations of glucagon and growth hormone remained unchanged, whereas glucose, C-peptide and cortisol increased on day 2. Noradrenaline concentrations increased during the stay at altitude, while adrenaline concentrations remained unchanged. In response to insulin infusion, catecholamines increased on day 2 (noradrenaline and adrenaline) and day 7 (adrenaline), but not at sea level. 4. In conclusion, insulin action decreases markedly in response to two days of altitude hypoxia, but improves with more prolonged exposure. HGP is always unchanged. The changes in insulin action may in part be explained by the changes in counter-regulatory hormones.
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PMID:The effect of altitude hypoxia on glucose homeostasis in men. 935 Jun 34

We compared glucoregulatory responses to intense exercise (14 min at 88% maximum O(2) uptake) between genders (16 men, 12 women). Analysis of covariance of maximum O(2) uptake showed no gender effect, with 82% of variance due to fat-free mass (FFM). Glycemia rose comparably during exercise but was higher in women during recovery (P = 0.02). Glucose production [rate of appearance (R(a)); in mg/min] increased markedly in both; stepwise multiple regression and analysis of covariance of R(a) (peak and incremental area under the curve) showed no effect of gender, body weight, or FFM. Glucose uptake [rate of disappearance (R(d))] increased less than R(a) and slower in women. R(d) area under the curve related to FFM (P = 0.01) but not gender or body weight. Norepinephrine and epinephrine responses (13-18x baseline) were the same and correlated significantly with R(a). Exercise insulin and glucagon changes were slight, but postexercise hyperinsulinemia was greater in women (P = 0.018), along with higher R(d). Therefore, intense exercise glucoregulation is qualitatively similar between genders, with a "feed-forward" regulation of R(a) (consistent with catecholamine mediation). However, women have a lesser R(d) response, related to FFM. This combination leads to greater recovery-period hyperglycemia and hyperinsulinemia.
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PMID:Gender differences in glucoregulatory responses to intense exercise. 1065 11

The glucoregulatory response to intense exercise [IE, >80% maximum O(2) uptake (VO(2 max))] comprises a marked increment in glucose production (R(a)) and a lesser increment in glucose uptake (R(d)), resulting in hyperglycemia. The R(a) correlates with plasma catecholamines but not with the glucagon-to-insulin (IRG/IRI) ratio. If epinephrine (Epi) infusion during moderate exercise were able to markedly stimulate R(a), this would support an important role for the catecholamines' response in IE. Seven fit male subjects (26 +/- 2 yr, body mass index 23 +/- 0.5 kg/m(2), VO(2 max) 65 +/- 5 ml x kg(-1) x min(-1)) underwent 40 min of postabsorptive cycle ergometer exercise (145 +/- 14 W) once without [control (CON)] and once with Epi infusion [EPI (0.1 microg x kg(-1) x min(-1))] from 30 to 40 min. Epi levels reached 9.4 +/- 0.8 nM (20x rest, 10x CON). R(a) increased approximately 70% to 3.75 +/- 0.53 in CON but to 8.57 +/- 0.58 mg x kg(-1) x min(-1) in EPI (P < 0.001). Increments in R(a) and Epi correlated (r(2) = 0.923, P </= 0.01). In EPI, peak R(d) (5.55 +/- 0.54 vs. 3.38 +/- 0.46 mg x kg(-1) x min(-1), P = 0.006) and glucose metabolic clearance rate (MCR, P = 0.018) were higher. The R(a)-to-R(d) imbalance in EPI caused hyperglycemia (7.12 +/- 0.22 vs. 5.59 +/- 0.22 mM, P = 0.001) until minute 60 of recovery. A small and late IRG/IRI increase (P = 0.015 vs. CON) could not account for the R(a) increase. Norepinephrine (approximately 4x increase at peak) did not differ between EPI and CON. Thus Epi infusion during moderate exercise led to increments in R(a) and R(d) and caused rises of plasma glucose, lactate, and respiratory exchange ratio in fit individuals, supporting a regulatory role for Epi in IE. Epi's effects on R(d) and MCR during exercise may differ from its effects at rest.
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PMID:Epinephrine infusion during moderate intensity exercise increases glucose production and uptake. 1078 Sep 53

The objective of the present study was to evaluate the effects of norepinephrine (n = 9) and dobutamine (n = 7) on carbohydrate and protein metabolism in healthy volunteers in comparison with a control group (n = 9). Norepinephrine (0.1 microg/kg min), dobutamine (5 microg/kg min), or placebo was infused for 240 min. The plasma concentration of glucose, lactate, epinephrine, norepinephrine, insulin, and glucagon were determined. Glucose and urea production and leucine flux were measured using a tracer technique. Norepinephrine caused a persisting rise in plasma glucose concentration, whereas the increase in glucose production was only transient. A minor increase in plasma lactate concentration was observed, but it did not exceed the physiological range. No change in leucine flux, urea production, or plasma concentration of insulin, glucagon, or epinephrine was found. Dobutamine slightly decreased glucose production, whereas the plasma concentration of glucose and lactate did not change. The reduction in leucine flux was paralleled by a decrease in urea production. No change in the plasma concentration of insulin, glucagon, or the catecholamines was observed. In conclusion, both norepinephrine and dobutamine have only minor metabolic effects. Because glucose production is enhanced by alpha1- and beta2-adrenoceptor stimulation, we conclude that dobutamine is only a weak agonist at these adrenoceptors. These minor metabolic actions may make both compounds suitable for critically ill patients because no further increase in metabolic rate should be caused.
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PMID:Metabolic effects of norepinephrine and dobutamine in healthy volunteers. 1246 55

Norepinephrine (NE) and epinephrine (Epi) help maintain normal blood glucose levels by stimulating glucagon release, glycogenolysis, and food consumption, and by inhibiting insulin release. The absence of NE and Epi in dopamine beta-hydroxylase-null (Dbh-/-) mice results in chronically low blood glucose levels, an impaired glucagon response to hypoglycemia, and elevated insulin levels. Nevertheless, Dbh-/- mice have normal glycogen levels and degrade it normally during a fast. Dbh-/- mice defend blood glucose levels better than controls in an insulin tolerance test but have increased sensitivity to glucose-stimulated insulin secretion and respond normally in a glucose tolerance test. Pharmacological evidence indicates that the hyperinsulinemia results from lack of alpha2-adrenoreceptor stimulation and increased parasympathetic tone. Dbh-/- mice eat normally after challenges with modest levels of insulin or 2-deoxyglucose but fail to eat under more extreme conditions when control mice still do. We suggest that the primary difference in Dbh-/- mice is chronic hyperinsulinemia associated with an altered glucose set point. However, these animals compensate for NE/Epi-mediated glycogenolysis and feeding.
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PMID:Norepinephrine and epinephrine-deficient mice are hyperinsulinemic and have lower blood glucose. 1295 68

The discovery of the adiposity signal leptin a decade ago revolutionised our understanding of the hypothalamic mechanisms underpinning the central control of ingestive behaviour. Subsequently, the structure and function of various hypothalamic peptide systems (Neuropeptide Y (NPY), Orexins, Melanocortins, Cocaine and Amphetamine Regulating Transcript (CART), Galanin/Galanin Like Peptides (GALP) and endocannabinoids) have been characterised in detail in rodent models. The therapeutic benefit of targeting these systems remains to be discovered. More is becoming known about the pharmacological potential of peripheral, meal-induced, episodic endogenous peptides. Hormones such as Cholecystokinin (CCK), Gastrin Releasing Peptides (GRP), Glucagon-Like Peptide I (GLP-1) Enterostatin, Amylin, Peptide YY (PYY) and Ghrelin are released prior to, during and/or after a meal, controlling intake and subjective feelings of appetite (hunger and satiety). In addition, there is an expanding body of literature detailing the effects of a wide variety of drugs on human appetite and food intake. Some of these drugs act upon CNS monoamine systems such as Serotonin (5-HT). Dopamine (DA) and Noradrenaline (NA), have long been implicated in appetite regulation. Detailed examination of both the effect of agonising endogenous gut peptide systems and the effect of various monoaminergic drugs on the expression of human appetite can provide a greater understanding of mechanisms underpinning normal appetite regulation. However, such an understanding must be based on knowledge of the effect of the treatment on meal size, eating rate, meal pattern, food choice and the subjective experience of appetite flux (hunger and satiety), and notjust food intake.
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PMID:The pharmacology of human appetite expression. 1505 9

Glucagon-like peptide (GLP)-1 is secreted rapidly from the intestine postprandially. We therefore investigated its possible neural regulation. With the use of isolated perfused porcine ileum, GLP-1 secretion was measured in response to electrical stimulation of the mixed, perivascular nerve supply and infusions of neuroactive agents alone and in combination with different blocking agents. Electrical nerve stimulation inhibited GLP-1 secretion, an effect abolished by phentolamine. Norepinephrine inhibited secretion, and phentolamine abolished this effect. GLP-1 secretion was stimulated by isoproterenol (abolished by propranolol). Acetylcholine stimulated GLP-1 secretion, and atropine blocked this effect. Dimethylphenylpiperazine stimulated GLP-1 secretion. In chloralose-anesthetized pigs, however, electrical stimulation of the vagal trunks at the level of the diaphragm had no effect on GLP-1 or GLP-2 and weak effects on glucose-dependent insulinotropic peptide and somatostatin secretion, although this elicited a marked atropine-resistant release of the neuropeptide vasoactive intestinal polypeptide to the portal circulation. Thus GLP-1 secretion is inhibited by the sympathetic nerves to the gut and may be stimulated by intrinsic cholinergic nerves, whereas the extrinsic vagal supply has no effect.
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PMID:Neural regulation of glucagon-like peptide-1 secretion in pigs. 1547 12

The purpose of this study was to define plasma catecholamine responses as part of the counterregulatory hormonal reaction to hypoglycemia in infants after a regular 3- to 4-h feed was omitted. Hormone levels were assessed once, at the end of the fast or at hypoglycemia. The 121 infants were subdivided into three groups for analysis: normoglycemia (n = 94, 78%); transient hypoglycemia (n = 11, 9%); or severe and persistent hypoglycemia (n = 16, 13%). The severe and persistent hypoglycemic group had significantly higher levels of cortisol and epinephrine than the normoglycemic group. Norepinephrine and glucagon levels did not differ between the groups. Human GH levels were higher in the transiently hypoglycemic group but not in the severe and persistent hypoglycemic group. Prefeed blood lactate levels differed significantly among the groups and were highest in the severe and persistent groups. Multiple regression analysis showed that cortisol levels were significantly higher in infants who had severe and persistent hypoglycemia. The counterregulatory hormonal response in infants to severe and persistent hypoglycemia was limited to elevations in only cortisol and epinephrine levels but did not involve glucagon or human GH. This limited hormonal response may also contribute to the frequent occurrence of hypoglycemia in these infants.
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PMID:Plasma catecholamines and the counterregulatory responses to hypoglycemia in infants: a critical role for epinephrine and cortisol. 1557 85

Untreated diabetic rats show impaired counterregulation against hypoglycemia. The blunted epinephrine responses are associated with reduced adrenomedullary tyrosine hydroxylase (TH) mRNA levels. Recurrent hypoglycemia further impairs epinephrine counterregulation and is also associated with reduced phenylethanolamine N-methyltransferase mRNA. This study investigated the adaptations underlying impaired counterregulation in insulin-treated diabetic rats, a more clinically relevant model. We studied the effects of insulin treatment on counterregulatory hormones and adrenal catecholamine-synthesizing enzymes and adaptations after recurrent hypoglycemia. Groups included: normal; diabetic, insulin-treated for 3 wk (DI); and insulin-treated diabetic exposed to seven episodes (over 4 d) of hyperinsulinemic-hypoglycemia (DI-hypo) or hyperinsulinemic-hyperglycemia (DI-hyper). DI-hyper rats differentiated the effects of hyperinsulinemia from those of hypoglycemia. On d 5, rats from all groups were assessed for adrenal catecholamine-synthesizing enzyme levels or underwent hypoglycemic clamps to examine counterregulatory responses. Despite insulin treatment, fasting corticosterone levels remained increased, and corticosterone responses to hypoglycemia were impaired in DI rats. However, glucagon, epinephrine, norepinephrine, and ACTH counterregulatory defects were prevented. Recurrent hypoglycemia in DI-hypo rats blunted corticosterone but, surprisingly, not epinephrine responses. Norepinephrine and ACTH responses also were not impaired, whereas glucagon counterregulation was reduced due to repeated hyperinsulinemia. Insulin treatment prevented decreases in basal TH protein and increased PNMT and dopamine beta-hydroxylase protein. DI-hypo rats showed increases in TH, PNMT, and dopamine beta-hydroxylase. We conclude that insulin treatment of diabetic rats protects against most counterregulatory defects but not elevated fasting corticosterone and decreased corticosterone counterregulation. Protection against epinephrine defects, both without and with antecedent hypoglycemia, is associated with enhancement of adrenal catecholamine-synthesizing enzyme levels.
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PMID:Effects of insulin treatment without and with recurrent hypoglycemia on hypoglycemic counterregulation and adrenal catecholamine-synthesizing enzymes in diabetic rats. 1639 86


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