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 effect of glucose hyperalimentation on energy metabolism in the cirrhotic rat liver after 70% hepatectomy was studied. After resection, rats received either 30 kcal/kg per day (group I) or 200 kcal/kg per day (group II) of glucose for 48 h. In both groups, hepatic mitochondrial ATP synthesis was accelerated when palmitic acid was used as substrate and suppressed when pyruvate was used. This suggests that the energy substrate of the remnant liver was principally fatty acids rather than glucose. Hepatic energy charge was within normal limits in group I, but decreased significantly in group II after hepatectomy. An abundance of glucose in the early postoperative period, therefore, caused a hepatic energy derangement by suppressing fatty acids utilization; this suppression was corroborated by the findings of lower immunoreactive glucagon and non-esterified fatty-acid concentrations in group II. To determine optimal glucose administration, the predicted value of glucose disposal rate (GDR) was calculated after an intravenous glucose tolerance test. GDR decreased significantly after hepatectomy and did not increase appreciably even with a large dose of insulin administration. These results suggest that glucose administration should be tailored to the GDR values after resection of the cirrhotic liver.
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PMID:Glucose overload and hepatic energy metabolism after resection of the cirrhotic liver in rats. 178 71

Cold exposure reverses the diabetogenic effects of high-fat feeding and markedly stimulates glucose uptake in rat brown adipose tissue (BAT). Considering that cold exposure increases the plasma levels of norepinephrine and lipolytic hormones, but decreases the levels of insulin, we have examined the effects of these agents on glucose transport in isolated rat brown adipocytes using D-[U-14C]glucose as a tracer. It was found that norepinephrine (0.1 microM), glucagon (0.1 nM) and ACTH (100 nM) all increased brown adipocyte respiration (2-10 times) and glucose transport (2-5 times). Studies with adrenergic agonists and antagonists revealed that norepinephrine increases glucose uptake via beta-adrenergic pathways. On the other hand, insulin also increased glucose transport (6 times) but inhibited (40-60 percent) the calorigenic effects of the lipolytic hormones. Both norepinephrine and glucagon potentiated the submaximal insulin responses for glucose transport, demonstrating the existence of metabolic interactions between norepinephrine-, glucagon-, and insulin-mediated glucose uptake. Remarkably, the stimulatory effects of these lipolytic agents were reproduced by dibutyryl cAMP (1 mM), isobutylmethylxanthine (0.1 mM) and palmitic acid (0.5 mM), suggesting that cAMP increases glucose transport via activation of lipolysis and thermogenesis. Considering that the stimulatory effects of norepinephrine (0.1 microM) on respiration and glucose transport were totally blocked by 2-tetradecylglycidic acid (50 microM), a specific inhibitor of mitochondrial carnitine acyl transferase, it is concluded that norepinephrine increases BAT glucose transport via fatty acid-activation of mitochondrial thermogenesis.
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PMID:Mechanism of norepinephrine stimulation of glucose transport in isolated rat brown adipocytes. 217 49

E series prostaglandins and their biologically active analogue, 16,16-dimethylprostaglandin E2 (dimethylprostaglandin E2), have inhibited hormone-stimulated glycogenolysis in hepatocytes cultured from male rats (Okumura, T., Sago, T. and Saito, K. (1988) Biochim. Biophys. Acta 958, 179-187). However, in the case of female rat hepatocytes, it is evident that dimethylprostaglandin E2 did not inhibit the glycogenolysis stimulated by glucagon, isoproterenol (beta-adrenergic response) or epinephrine (with propranolol, alpha 1-adrenergic response) in cultures on day 1. Dimethylprostaglandin E2 inhibited such hormone-stimulated glycogenolysis in cultures on day 2 and 3, but to a lesser extent than in the male-derived cells. The concentration for 50% inhibition was approx. 10(-8) M; inhibition was completely blocked by a pertussis toxin. Prostaglandin E2 had the same effect as dimethylprostaglandin E2; prostaglandins D2 and F2 alpha had no effect. Additions of sex hormones, 17 beta-estradiol and testosterone, and palmitic acid (diminishing the prostaglandin catabolism) to the culture medium did not change the effect of dimethylprostaglandin E2. These data indicate that a sex difference exists in the inhibition of hepatic glycogenolysis by prostaglandin E2 and its analogue in rat cultured hepatocytes, although the factor causing such a difference is a present unknown.
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PMID:A sex difference in the effect of prostaglandins on hormone-stimulated glycogenolysis in primary cultures of rat hepatocytes. 231 Jul 80

We have used primed constant infusions of [1-13C]palmitic acid, [2-3H]glycerol, and [U-14C]glucose to evaluate the response of glucose and fat kinetics to alpha or beta adrenergic blockade in conscious dogs. The response of each blocking agent was evaluated both with and without control of the glucoregulatory hormones. When hormones were controlled, somatostatin and metyrapone were infused to block hormonal secretion, and insulin, glucagon, growth hormone, and cortisol were replaced at basal physiological rates. alpha blockade (beta stimulation) did not influence glucose production or oxidation, but it did decrease glucose clearance when hormones were controlled. Clearance did not decrease during blockade when hormones were not controlled, presumably because of the resulting increase in the plasma insulin concentration. Glucose production, plasma glucose concentration, and glucose oxidation all increased with beta blockade (alpha stimulation). alpha blockade (beta stimulation) resulted in an increase in lipolysis, whereas beta blockade (alpha stimulation) resulted in a decrease in lipolysis. In neither case, however, did FFA oxidation change. We conclude that (a) the predominant effect of unopposed stimulation is the stimulation of lipolysis, whereas unopposed alpha stimulation inhibits lipolysis. Direct effects of either alpha or beta stimulation on glucose kinetics are less dramatic, but both alpha and beta stimulation decrease glucose clearance.
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PMID:The integrated effect of adrenergic blockade on glucose, fatty acid, and glycerol kinetics: responses in the basal state and during hormonal control with somatostatin-hormonal infusion. 288 Oct 26

The hepatic level of prostaglandins will reflect the balance between synthesis of prostaglandins and their rapid catabolism via beta-oxidation by hepatocytes. In the present study we examined the effect of physiological fuel substrates on the breakdown and action of prostaglandin E2 (PGE2) in isolated rat hepatocytes. Palmitic acid (0.32 mM), a long-chain fatty acid, inhibited the rate of PGE2 breakdown (10(-7) M) by approx. 80%. As the palmitic acid concentration was increased from 0 to 0.8 mM, the percentage of PGE2 remaining in the incubation 5 min following prostaglandin addition was raised from approx. 10% to over 98%. Octanoic acid (0.8 mM) also inhibited PGE2 catabolism, while butyric acid (0.8 mM) and pyruvic acid (2.5 mM) were without effect. The inhibition of glucagon-stimulated glycogenolysis by PGE2 was increased in the presence of 0.6 mM palmitic acid, consistent with decreased PGE2 catabolism. These studies demonstrate that changes within the range of free fatty acid concentrations seen physiologically in vivo may dramatically alter PGE2 catabolism and, therefore, the effect of PGE2 to modulate hormonal action in the liver.
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PMID:Modulation of prostaglandin E2 catabolism and action by fuel substrates in rat hepatocytes. 291 5

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.
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PMID:Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion. 389 May 59

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.
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PMID:Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs. 609 72

Using a continuous infusion of [1-13C] palmitic acid tracer, plasma palmitate turnover was measured 14 times in nine bandaged, thermally injured adults. Plasma glucose (102 +/- 4 mg/dl), insulin (21 +/- 4 microU/ml), and glucagon (296 +/- 34 pg/ml) levels were significantly elevated compared with values in uninjured controls. Circulating plasma epinephrine (67 +/- 11 pg/ml) and norepinephrine (219 +/- 57 pg/ml) levels were more than twofold their respective control values of 261 +/- 4 pg/ml and 211 +/- 7 pg/ml but less than the previously defined plasma threshold levels for lipolytic effects of these catecholamines as circulating hormones. Plasma palmitate and free fatty acid concentrations, 113 +/- 8 and 452 +/- 38 microM, respectively, were not different from control values but palmitate flux (2.66 +/- 0.28 mumol kg-1 min-1) and free fatty acid turnover calculated therefrom (10.53 +/- 1.13 mumol kg-1 min-1) were significantly elevated compared to the control rates. While palmitate turnover significantly correlated with plasma palmitate concentration and with per cent body surface area burned, there was no relationship between palmitate flux and circulating epinephrine or norepinephrine levels. These data raise new questions about the relative catabolic roles of catecholamines in bandaged, thermally-injured patients.
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PMID:Plasma palmitate turnover in subjects with thermal injury. 638 97

Previous study from our laboratory demonstrated that an increased release of gut glucagon-like immunoreactivity (GLI) following triglyceride digestion was not observed in pancreatectomized dogs. Therefore, in order to clarify the response of gut GLI to triglyceride ingestion, experimental study was carried out in normal and pancreatectomized dogs. When butter was administered to pancreatectomized dogs in combination with pancreatic enzymes, plasma glucagon (IRG) measured by specific antiserum did not change significantly but plasma triglyceride as well as plasma total immunoreactive glucagon (total IRG) measured by nonspecific antiserum increased. Oral administration of glycerol induced no significant increase in plasma IRG but elicited a moderate increase of plasma total IRG. Gastric instillation of palmitic acid induced a remarkable rise of plasma total IRG in normal dogs, whereas plasma IRG did not reveal any changes. Oral administration of triglyceride of medium chain fatty acid, tricaprylin, did not promote any rise of plasma IRG but a slight increase of plasma total IRG. From the present experiment, it is concluded that hydrolysis of triglyceride and its metabolites are important in the release of gut GLI following fat ingestion. Among its metabolites, long chain fatty acid and glycerol promote the GLI secretion, whereas medium chain fatty acid does not.
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PMID:Characterization of response of gut GLI to fat ingestion in dogs. 639 48

1. Rats were fed to appetite on a stock laboratory diet or on diets consisting of the stock diet and in addition 50 or 200 g triolein/kg, 50 g palmitic acid/kg or 50 g/kg of a concentrate mixture of methyl branched-chain fatty acids (Me-BCFA) which had been prepared from sheep adipose triacylglycerols. 2. No differences could be detected in the delta 9-desaturase activity or fatty acid synthetase activity of liver preparations from rats which had been fed on either the stock diet, the 50 g palmitic acid/kg or the 50 and 200 g triolein/kg diet; the palmitic acid diet was therefore taken as the control diet in subsequent experiments. 3. Rats consuming the 50 g Me-BCFA/kg diet exhibited a marked reduction in the capacity of their liver microsomes for delta 9-desaturation when compared with animals receiving the control diet. The delta 6-desaturase activity also showed an inhibitory trend with the Me-BCFA diet. 4. Microsomal omega-oxidation of fatty acids, mitochondrial succinate oxidation and the activity of cytosolic fatty acid synthetase (FAS) were unaffected by the ingestion of the Me-BCFA mixture compared with the diet which included palmitic acid. 5. There were no differences in the plasma concentration of thyroxin, insulin and glucagon between animals fed on the diets containing palmitic acid or the Me-BCFA. 6. For a given concentration of fatty acids the Me-BCFA had a greater inhibitory effect when added to incubations of liver microsomes from rats fed on the standard diet than did the addition of palmitic acid. 7. The observations in vivo and in vitro strongly suggested that the Me-BCFA were having a specific inhibitory effect on the desaturation reaction.
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PMID:The effect of dietary methyl branched-chain fatty acids on aspects of hepatic lipid metabolism in the rat. 705 69


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