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

The effects of chronic (72 h) glucagon treatment on active nutrient uptake by the rat jejunum have been determined using in-vitro electrophysiological and autoradiographic methods together with an in-vivo technique which measures absorption across a cannulated segment of upper jejunum. Glucagon caused a marked increase in the potential difference across the brush border membrane from a mean value of -47.6 mV under control conditions to -54.2 mV following treatment with the hormone (P less than 0.025). A similar hyperpolarization was also noted after 24 h glucagon administration. The magnitude of the depolarization induced by the addition of D-galactose (4 mmol/l) to the mucosal fluid was increased from 6.0 to 14.3 mV following 72 h glucagon treatment (P less than 0.05). Phloridzin (0.1 mmol/l) abolished the galactose-induced depolarization in both control and treated animals. Glucagon induced significant increases of 49.9 and 61.0% respectively for glucose and galactose absorption measured under in-vivo conditions. Autoradiographic studies revealed that following glucagon treatment, L-valine uptake occurred earlier during enterocyte migration along the villus. This resulted in an enhanced accumulation of the amino acid at the villus tip. We conclude that glucagon increases nutrient transport across the small intestine. The raised electrical gradient for Na+- coupled nutrient entry into the enterocyte is likely to be a major factor in the transport response.
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PMID:Hyperglucagonaemia: effects on active nutrient uptake by the rat jejunum. 378 84

We have investigated catecholamine-glucagon-insulin interactions using three stress models: 1) hypoglycemia; 2) exercise; and 3) epinephrine infusion. Phlorizin caused mild hypoglycemia with hypoinsulinemia. Plasma glucagon increased as did hepatic glucose production. Catecholamines did not increase. Insulin caused severe hypoglycemia. Metabolic counterregulation was due mainly to the 40-fold increase in epinephrine. Glucagon played a role only in the recovery from insulin-induced hypoglycemia, which could reflect increased hepatic sensitivity to glucagon with declining plasma insulin. Glucagon suppression during exercise caused transient hypoglycemia due to an inadequate rise in glucose production. Exaggerated epinephrine release during hypoglycemic exercise prevented severe hypoglycemia by inhibiting glucose utilization and stimulating glucose production, with an associated increase in lactate and free fatty acid levels. Hypoglycemic exercise also caused increased cortisol release. Counterregulation was prevented by a euglycemic clamp. We conclude that, during exercise, glucagon is directly responsible for 80% of the increment of glucose production and controls glucose uptake by the muscle indirectly; thus glucagon spares muscle glycogen by increasing hepatic glucose production. Epinephrine infusion in normal dogs caused a transient increase in glucose production and a sustained inhibition of glucose clearance, resulting in hyperglycemia. Insulin rose transiently, followed by a relative inhibition of secretion. Glucagon suppression did not modify the metabolic effects of epinephrine. In alloxan-diabetic dogs, the glucagon response to epinephrine was augmented, whereas in depancreatized dogs, during subbasal insulin infusion, the hepatic response to glucagon was excessive. Glucagon suppression diminished hepatic responsiveness to epinephrine in both models. Stress-induced diabetic instability could relate to exaggerated glucagon release or to increased hepatic sensitivity to glucagon. Thus, during hypoglycemia, exercise, or epinephrine infusion, prevailing plasma insulin levels govern the relative metabolic roles of epinephrine and glucagon.
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PMID:Catecholamine responses and their interactions with other glucoregulatory hormones. 614 92

Phlorizin and 1,3-butanediol were used to determine effects of glucosuria and ketonemia on concentrations of metabolites in blood plasma and on kinetics of glucose metabolism. Four steers received four treatments (control; control plus dietary 1,3-butanediol; control plus phlorizin injections; and control plus phlorizin and 1,3-butanediol) in a Latin square design. Treatments lasted 14 days. All steers received a 30% grain, 70% forage ration in equal meals every 2 h. Metabolite concentrations in blood plasma and urine and glucose kinetics were measured on each of the last 3 days of each treatment period. Phlorizin caused glucosuria; decreased plasma glucose, glucose total entry rate, and glucose recycling; and increased plasma free fatty acids and glucose irreversible loss. Glucose pool size was increased by 1,3-butanediol. Phlorizin plus 1,3-butanediol caused glucosuria and ketonuria; decreased plasma glucose; and increased blood ketone bodies, plasma free fatty acids, glucose irreversible loss, and glucose pool size. Growth hormone, insulin, and glucagon were not affected by treatment. Physiological perturbations in these steers were characteristic of some of those in ketotic cows.
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PMID:Glucose kinetics, plasma metabolites, and endocrine responses during experimental ketosis in steers. 638 28

Adaptations of in vitro incorporation of gluconeogenic substrates into glucose and adaptations of metabolite concentrations of liver to subcutaneous phlorizin and dietary 1,3-butanediol were examined for liver samples from dairy steers. Later, the same adaptations were examined after 6 days of feed restriction. Feeding 1,3-butanediol significantly decreased conversion of carbon-14 of lactate and propionate to glucose and to carbon dioxide. There were no changes of concentrations of hepatic glycogen or triglyceride, and increases were only minor for beta-hydroxybutyrate concentration. Both phlorizin, with or without 1,3-butanediol, and feed restriction significantly increased rates of carbon incorporation into glucose from aspartate, lactate, and propionate but did not change rates of oxidation to carbon dioxide. Phlorizin had no effect on hepatic glycogen or triglyceride concentrations, but feed restriction decreased liver glycogen and increased triglyceride concentrations. Changes associated with either phlorizin treatment or feed restriction are consistent with a decreased ratio of insulin to glucagon of blood plasma. When combined, phlorizin and 1,3-butanediol seem to have some utility for developing a ketosis model.
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PMID:In vitro hepatic gluconeogenesis during experimental ketosis produced in steers by 1,3-butanediol and phlorizin. 650 46

Phloridzin, an inhibitor of renal sugar transport, produces an important loss of glucose in urine of treated animals. In order to reduce severely the maternal glucose supply to the fetuses in short-term experiments, we have combined phloridzin administration to pregnant rats with 18 h starvation. Fetuses from starved phloridzin-treated mothers were compared with fetuses from starved mothers. Combined treatment markedly decreases fetal blood glucose concentration (-36%) and fetal liver glycogen stores (-76%). These changes are associated with a decrease in plasma insulin (-25%), a rise in plasma glucagon (+120%) and a marked increase of hepatic PEPCK activity (+400%). It appears from these results that phloridzin treatment for a short duration is able to induce glycogenolysis and the premature appearance of PEPCK in the liver of rat fetuses.
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PMID:Fetal metabolic response to phloridzin-induced hypoglycemia in pregnant rats. 699 14

Liver insulin resistance and glucagon-stimulated hepatic glucose production are characteristics of the diabetic state. To determine the potential role of glucose toxicity in these abnormalities, we examined whether phlorizin treatment of streptozotocin-diabetic rats resulted in altered expression of genes involved in key steps of hepatic glucose metabolism. By inhibiting renal tubular glucose reabsorption, phlorizin infusion to diabetic rats induced normoglycaemia, did not significantly alter low circulating insulinaemia, but caused a marked decrease in hyperglucagonaemia. Glucokinase and L-type pyruvate kinase mRNA levels were reduced respectively by 90% and 70% in fed diabetic rats, in close correlation with changes in enzyme activities. Eighteen days of phlorizin infusion partially restored glucokinase mRNA and activity (40% of control levels), but had no effect on L-type pyruvate kinase mRNA and activity. In contrast to the glycolytic enzymes, mRNA and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase were increased (10- and 2.2-fold, respectively) in fed diabetic rats. Phlorizin administration decreased phosphoenolpyruvate carboxykinase mRNA to values not different from those in control rats, while phosphoenolpyruvate carboxykinase activity remained 50% higher than that in control rats. The 50% rise in liver glucose transporter (GLUT 2) mRNA and protein, produced by diabetes, was also corrected by phlorizin treatment. In conclusion, we propose that phlorizin treatment of diabetic rats may induce a partial shift of the predominating gluconeogenesis, associated with hepatic glucose overproduction, into glycolysis, by correction of impaired pre-translational regulatory mechanisms. This could be essentially mediated through improved pancreatic alpha-cell function and subsequent lowering of hyperglucagonaemia. These observations suggest that glucagon-stimulated hepatic glucose production may result, in part, from glucose toxicity.
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PMID:Phlorizin treatment of diabetic rats partially reverses the abnormal expression of genes involved in hepatic glucose metabolism. 847 72

The metabolic effects of a phlorizin-induced drainage of glucose were studied in six lactating ewes with or without peroral alanine drenches in a study of crossover design. Phlorizin gave rise to a small, but significant, elevation of plasma beta-hydroxybutyrate. The plasma level of alanine decreased by about 30% due to the phlorizin injections and alanine was negatively correlated to beta-hydroxybutyrate. The plasma level of free fatty acids increased due to phlorizin. Plasma insulin and glucose concentrations were not significantly affected by phlorizin while glucagon level showed a small but significant increase. Peroral alanine drenches to phlorizin-treated ewes gave rise to a transitory elevation of alanine in plasma. The plasma level of free fatty acids was about 40% lower in phlorizin-treated ewes receiving alanine and beta-hydroxybutyrate tended to be lower (P < 0.08). We suggest that beta-hydroxybutyrate, apart from its function as an oxidative fuel, might play an important role by limiting glucose oxidation and protein degradation in skeletal muscles during periods of negative energy balance in ruminants. Furthermore, it is suggested that alanine supplementation decreases lipolysis and ketogenesis in lactating ewes.
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PMID:Effects of peroral alanine administration in lactating ewes with decreased availability of glucose. 938 2

Phloridzin-insensitive D-glucose uptake into enterocytes isolated sequentially from along the crypt-villus axis showed the majority of transport activity to reside in cells from the upper third of the villus. In contrast, total postnuclear glucose transporter 2 (GLUT2) protein content of the cells was high even close to the crypt and was almost constant for the upper 80% of the villi. A 4 h lumenal perfusion in vivo with 100 mM D-glucose prior to harvesting the enterocytes produced a 2- to 3-fold increase in phloridzin-insensitive D-glucose uptake which extended down 70% of the villus. Vascular infusion in vivo with either 800 pM gastric inhibitory polypeptide (GIP) or glucagon-like peptide-2 (GLP-2) prior to harvesting enterocytes produced the same response as lumenal glucose, while glucagon like peptide-1 (GLP-1) had no effect. Inclusion of 30 microM brefeldin A (BFA), an inhibitor of protein trafficking, in the lumenal perfusate produced a small, but not significant, increase in the control uptake profile along the villus in isolated enterocytes. However, BFA significantly reduced the upregulation induced by lumenal glucose and vascular GIP and blocked the stimulation produced by vascular GLP-2. Biotinylation of surface proteins and isolation with protein A indicated that there was no change in the membrane abundance of GLUT2 after GLP-2 treatment. These results are discussed in relation to the role of gastrointestinal peptide hormones in controlling intestinal hexose transport and the possibility of protein trafficking being involved in mediating the upregulation of GLUT2 activity in the enterocyte basolateral membrane.
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PMID:Basolateral D-glucose transport activity along the crypt-villus axis in rat jejunum and upregulation induced by gastric inhibitory peptide and glucagon-like peptide-2. 979 81

Individuals with type 1 diabetes demonstrate a hypoglycemia-specific defect in glucagon secretion. To determine whether intraislet hyperinsulinemia plays a role in the genesis of this defect, glucagon-secretory responses to moderate hypoglycemia induced by either insulin or a novel combination of the noninsulin glucose-lowering agents 5-aminoimidazole-4-carboxamide (AICAR) and phlorizin were compared in diabetic BB rats (an animal model of type 1 diabetes) and nondiabetic BB rats. The phlorizin-AICAR combination was able to induce moderate and equivalent hypoglycemia in both diabetic and nondiabetic BB rats in the absence of marked hyperinsulinemia. Diabetic BB rats demonstrated impaired glucagon and epinephrine responses during insulin-induced hypoglycemia compared with nondiabetic rats. In contrast, both glucagon (9- to 10-fold increase) and epinephrine (5- to 6-fold increase) responses were markedly improved during phlorizin-AICAR hypoglycemia. Combining phlorizin, AICAR, and insulin attenuated the glucagon response to hypoglycemia by 70% in the diabetic BB rat. Phlorizin plus AICAR had no effect on counterregulatory hormones under euglycemic conditions. We conclude that alpha-cell glucagon secretion in response to hypoglycemia is not defective if intraislet hyperinsulinemia is prevented. This suggests that exogenous insulin plays a pivotal role in the etiology of this defect.
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PMID:AICAR and phlorizin reverse the hypoglycemia-specific defect in glucagon secretion in the diabetic BB rat. 1237 37

The ability of several drugs to restore directly elicited twitches of the rat diaphragm depressed by excess potassium chloride has been studied. The drugs found to be effective were sympathomimetic amines, insulin, glucagon, caffeine, theophylline, calcium chloride and hexosephosphates. The effects of the sympathomimetic amines and glucagon were blocked by beta-receptor blocking agents. Phloridzin blocked the effect of insulin and depressed that of glucagon. The increase in twitch tension still occurred under anaerobic conditions and was not abolished by the glycolytic inhibitor, iodoacetate. All of the effective drugs are known to affect carbohydrate metabolism and the suggestion by Ellis (1955) that the effect on contractions may be a result of increased intracellular hexosephosphate levels is discussed.
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PMID:THE EFFECTS OF ADRENALINE AND OTHER DRUGS AFFECTING CARBOHYDRATE METABOLISM ON CONTRACTIONS OF THE RAT DIAPHRAGM. 1420 94


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