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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a non-recirculating perfusion system, we studied the time course of ketone body output from the isolated rat liver in response to various hormones and changes in pH and redox state. The release of 3-hydroxybutyrate (3-OHB) started to be suppressed within 1 min after the addition of insulin (50 mU/ml) and kept half of the basal level even 10 min after its cessation. The addition of glucagon (0.2 microM) caused an increase in both 3-OHB and acetoacetate (AcAc) outputs from fed livers within 5 min, which reached about 150% of the basal level 10 min after the infusion and maintained a constant level through out the experiment. Growth hormone (2 mu/ml) elicited a slight but significant increase in AcAc output soon after the infusion. Epinephrine (10 microM) also caused a slight increase in both AcAc and 3-OHB outputs 9 min after the infusion and maintained a significant increase even 10 min after stopping infusion. The decrease in pH of the perfusate or the addition of ascorbic acid abruptly suppressed the AcAc production. In summary, the present study clearly demonstrated the direct effects of various hormones on ketogenesis in the liver and the usefulness of a non-recirculating liver perfusion system as a tool for the study of ketogenesis.
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PMID:Time course of ketone body production in the isolated perfused rat liver in response to various stimuli. 355 47

Milk intake suppression after intraperitoneal glucagon and epinephrine injections was studied in liver-denervated [hepatic vagal branch transection (VAG-B), hepatic artery-portal vein denervations (H-ART), or total denervation (TOTAL)] and sham-operated rats (SHAM). In experiment 1, glucagon (500 micrograms/kg, Sigma) had no effect on 30 min of milk intake but produced hyperglycemia in all groups. Glucagon (750 micrograms/kg, Sigma; 400 micrograms/kg, Lilly) decreased intake in all groups, as did epinephrine (30 micrograms/kg). In experiment 2, TOTAL and SHAM were tested with 50, 100, and 400 micrograms/kg of glucagon (Lilly). Only the two larger doses suppressed milk intake of both groups, whereas all doses caused hyperglycemia. Epinephrine (30 micrograms/kg) decreased food intake more than glucagon but caused less hyperglycemia than any glucagon dose. In experiment 3, VAG-B and SHAM groups were given glucagon (400 micrograms/kg, Lilly), which reduced their intake. Under these test conditions, liver innervation is not required for glucagon and epinephrine to suppress milk intake. The ability of the two hormones to suppress ingestion appears to be dissociated from their hyperglycemic actions.
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PMID:Glucagon and epinephrine suppression of food intake in liver-denervated rats. 374 Mar 18

Changes in subcellular distribution of adenine nucleotides, mitochondrial/cytosolic proton gradients, rates of respiration, gluconeogenesis (fasted state) and glycogenolysis (fed state) were studied in isolated perfused rat livers following addition of glucagon (10(-8) M) or adrenaline (10(-7) M). Glucagon increased the gradient in all states. The cytosolic ATP/ADP ratio was increased in the fasted but decreased in the fed state which is consistent with a diminished futile cycling in gluconeogenesis (fasted state) or a decreased glycolytic rate (fed state). Adrenaline caused an increase in the proton gradient and the mitochondrial ATP/ADP ratio. The two effects are attributed to increased calcium entry into the matrix space.
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PMID:Control of energy metabolism by glucagon and adrenaline in perfused rat liver. 374 64

The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose concentration and rates of production and utilization of glucose were similar in denervated rats and control rats. Also hepatic glycogen depletion was similar in the groups. The lack of effect of denervation could not be ascribed to compensating changes in hormone or substrate levels. In adrenodemedullated rats lack of glucose recovery from hypoglycemia was accompanied by delayed normalization of glucose clearance. In fed rats, activity in hepatic autonomic nerves is not a primary mechanism increasing glucose production during acute hypoglycemia. Epinephrine enhances glucose recovery by decreasing glucose clearance rather than by increasing glucose production, at least when glucagon is present.
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PMID:Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats. 388 3

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

Basal adenyl cyclase activity and its response to epinephrine and glucagon were studied in isolated adipocyte ghosts obtained from fed, starved, refed, and fat-diet-adapted rats. Epinephrine stimulation of adenyl cyclase was significantly increased in fasted rats, but the glucagon response did not change. Rats fasted for 48 hr and refed a high carbohydrate, low fat diet for 48 or 96 hr showed no differences from chow-fed animals in either basal or hormone-stimulated adenyl cyclase activity. Rats adapted to a high fat, low carbohydrate diet showed an initial and transitory increase in basal activity but a progressive loss of epinephrine- and glucagon-stimulated enzyme activities. The loss in hormone responsiveness correlated well with a decrease in hormone-stimulated lipolysis of fat pads and was associated with a significant increase in fat cell diameter.
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PMID:Effects of starvation, refeeding, and fat feeding on adipocyte ghost adenyl cyclase activity. 433 99

1. Protein kinase activity was measured in islets of Langerhans that had been incubated in the presence of agents known to affect insulin release. 2. Glucagon, theophylline, caffeine and 3-isobutyl-1-methylxanthine, agents that raise cyclic AMP concentrations in islet cells and stimulate insulin release, increased protein kinase activity. Adrenaline and diazoxide, agents that decrease cyclic AMP concentrations and inhibit insulin secretion, decreased the activity. 3. The increase in protein kinase activity produced by different concentrations of 3-isobutyl-1-methylxanthine was apparently related to the increase in intracellular concentrations of cyclic AMP. 4. The sulphonylureas, tolbutamide and glibenclamide, agents that increase insulin release, also increased the protein kinase activity; however, leucine, arginine and xylitol, which also stimulate insulin release, were without effect on the kinase activity. 5. Increasing the glucose concentration of the incubation medium from 2 to 20mm had no effect on protein kinase activity. Further, the ability of 3-isobutyl-1-methylxanthine to increase the protein kinase activity was not affected by the glucose concentration of the incubation medium. 6. These results suggest that agents which affect insulin secretion by altering cyclic AMP concentrations may exert their effects on hormone release by altering the activity of a cyclic AMP-dependent protein kinase in islet cells.
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PMID:The mode of action of adenosine 3':5'-cyclic monophosphate in mammalian islets of Langerhans. Effects of insulin secretagogues on islet-cell protein kinase activity. 435 86

1. Intracellular recordings of membrane potential were made from superficial cells of isolated mouse liver segments superfused with physiological salt solutions.2. The mean resting cell membrane potential was -39.4 mV.3. Glucagon caused a dose-dependent membrane hyperpolarization which was detectable at 10(-9)M and maximal (7 mV) at 10(-7)M. The hyperpolarization started within half a minute after exposure to glucagon. Secretion (2 x 10(-7)M) had no effect on the membrane potential.4. Adrenaline (10(-6)M) and isoprenaline (10(-6)M) also caused membrane hyperpolarization (4-6 mV). The effect of isoprenaline, but not that of adrenaline, was blocked by propranolol (5 x 10(-6)M).5. Dibutyryl adenosine 3',5'-monophosphate (10(-3)M) caused a membrane hyperpolarization of 4-8 mV.6. In the absence of extracellular K or the presence of Strophanthin-G (10(-3)M) the resting potential was decreased and the response to glucagon reduced. During exposure to a solution containing 20 mM-K the resting potential was slightly enhanced and the amplitude of the glucagon-induced hyperpolarization reduced compared with control conditions.7. It is concluded that the effect of glucagon on the membrane potential is due to an interaction with specific membrane receptors probably leading to activation of the membrane-bound adenyl cyclase. It is probable that the hyperpolarization is mediated by cyclic AMP. The hyperpolarization induced by glucagon is dependent on a normal function of the membrane Na-K pump.
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PMID:The effect of glucagon on the liver cell membrane potential. 436 92

1. The inotropic activity of glucagon was compared with catecholamines and cardiac glycosides by in vitro procedures which were able to differentiate between the activities of the latter two groups.2. The frequency-force curve for glucagon resembled that of noradrenaline at low stimulation frequencies (1 and 2/min) and that of ouabain at more rapid frequencies of stimulation.3. Noradrenaline and adrenaline increased the amplitude of contraction of cat papillary muscles and markedly shortened the time to reach peak tension. Ouabain and glucagon increased tension without any change in the time to peak tension.4. Noradrenaline caused a rapid onset and rate of rise of contraction of cat aortic strips, whereas the response to ouabain was slow in onset and rate of development. Glucagon had no effect on this preparation, even at high concentrations.5. Manganese ions caused a shift of the dose-response curve to ouabain and glucagon, but not to noradrenaline or calcium. In 0.5 mM Ca media, the response to ouabain was abolished and the curve to noradrenaline shifted.6. When glucagon was added to an atrial preparation, the time to the initial increase in tension and the time to maximal tension was intermediate between that necessary for noradrenaline and that necessary for cardiac glycosides.7. Propranolol blocked the inotropic response to noradrenaline, but not to either ouabain or glucagon.8. A relative measure of contraction-dependency was described. Cardiac glycosides exhibited a greater degree of contraction-dependency than either noradrenaline or glucagon.9. Adrenaline elevated the depressed plateau of the action potential from calf and sheep Purkinje fibres, but ouabain and glucagon were without effect.10. Electrophysiological measurements demonstrated that moderate concentrations of glucagon exerted only a small effect in prolonging atrial and ventricular action potentials.11. Several pharmacological blocking drugs and other inotropic agents did not potentiate or block the inotropic response to glucagon. Reserpine pretreatment increased the response to glucagon.12. It was concluded that glucagon has its own spectrum of inotropic activity and does not completely mimic the effects of either ouabain or noradrenaline.
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PMID:Comparison of the inotropic response to glucagon, ouabain and noradrenaline. 549 91

The metabolism of the large mass of adipose tissue constituting the fat tail of the Syrian sheep has been investigated by measuring arteriovenous concentration (A-V) differences. The tail in situ in the intact anesthetized animal, as well as the isolated tail perfused with blood through a constant flow pump oxygenator, was used. In fed animals, the adipose tissue took up glucose and ketone bodies and released lactate and free fatty acids (FFA), although in some animals uptake of FFA also occurred. After 48-144 hr of fasting, uptake of glucose and ketone bodies continued and the FFA release increased. Total lipid esters and phospholipids were not released even after food had been withheld for 6 days. Insulin increased the A-V difference and the uptake of glucose, and reduced the FFA release. Adrenaline increased the A-V difference and uptake of glucose; the simultaneous increase in serum FFA was not accompanied by an increase in A-V difference for FFA in most experiments, which suggests that this adipose tissue is relatively insensitive to the lipolytic effect of the hormone. The effect of noradrenaline was similar to that of adrenaline. Glucagon hyperglycemia was not accompanied by increase in glucose uptake in most experiments.
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PMID:Metabolism of adipose tissue in the fat tail of the sheep in vivo. 595 67


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