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)

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

The hypothesis was made of an increased oxidation of fatty acids (FFA) and a decrease of their esterification rate contributing to the islet secretory defect during starvation. 2-Bromostearate (BrS), a FFA-oxidation inhibitor, was therefore tested on the islet secretion of insulin, glucagon and somatostatin stimulated by glucose or palmitate under fasted or fed conditions. Starvation for 48 h blocked both the glucose-induced stimulation and inhibition of insulin and somatostatin and the glucagon secretion. BrS completely restored the insulin response and stimulated both somatostatin and glucagon-basal release, the latter inhibition by glucose being partially recovered. Palmitate transient stimulation of insulin and somatostatin and inhibition of glucagon release was turned into a sustained increase in all three cases by addition of BrS. The potentiation by BrS of palmitate secretory effects in "fed" islets and of hormone release in "fasted" islets, apparently suggest that inhibition of FFA-oxidation may play a role in the regulation of islet secretion.
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PMID:Starvation-induced secretory changes of insulin, somatostatin, and glucagon and their modification by 2-bromostearate. 614 16

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

Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is an enzyme that catalyzes conversion of glycine-extended peptides to alpha-amidated bioactive peptides. Two peptides that are processed at their carboxyl-termini by this enzyme are neuropeptide Y and anglerfish peptide Y, both of which possess a C-terminal glycine that is used as a substrate for amidation. Results from previous reports have demonstrated that neuropeptide Y-like and anglerfish peptide Y-like immunoreactivities are present in the brain of anglerfish (Lophius americanus). Furthermore, neuropeptide Y-like peptides, namely anglerfish peptide Y and anglerfish peptide YG (the homologues of pancreatic polypeptide) are present in the islet organ of this species. Neuropeptide Y has also been localized in the anterior, intermediate and posterior lobes of the pituitary gland in a variety of species. In order to learn more about the distribution of the enzyme responsible for alpha amidation of these peptides in the brain and pituitary and to specifically investigate the relationship of this enzyme to peptide synthesizing endocrine cells of the anglerfish islet, we performed an immunohistochemical study using several antisera generated against different peptide sequences of the enzyme. PAM antisera labeled cells in the islet organ, pituitary and brain, and fibers in the brain and pituitary gland. The PAM staining pattern in the brain was remarkably similar to the distribution of neuropeptide Y immunoreactivity reported previously. Clusters of cells adjacent to vessels in the anterior pituitary displayed punctate PAM immunoreactivity while varicose fibers were observed in the pituitary stalk and neurohypophysis. Endocrine cells of the islet organ were differentially labeled with different PAM antisera. Comparison of the staining patterns of insulin, glucagon, and anglerfish peptide Y in the islet organ to PAM immunoreactivity suggests a distribution of forms of PAM enzyme in insulin and anglerfish peptide Y-containing cells, but no overlap with glucagon-producing cells. The results also indicate that PAM immunoreactivity is widely distributed in the brain, pituitary and islet organ of anglerfish in cells, that contain peptides that require presence of a C-terminal glycine for amidation.
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PMID:Distribution of peptidyl-glycine alpha-amidating monooxygenase immunoreactivity in the brain, pituitary and islet organ of the anglerfish (Lophius americanus). 775 Jan 30

Clinical studies and experiments in rats were carried out to elucidate changes in fuel utilization after hepatectomy. In addition, the effect of glucose hyperalimentation on energy metabolism in the liver remnant was studied. Respiratory quotient (RQ) and substrate oxidation rate for fat and glucose were evaluated by indirect calorimetry in eight patients who had undergone liver resection. Patients had a reduced nonprotein RQ of approximately 0.85 and a reduced ratio of glucose to fat oxidation of approximately 2.0 on the 1st and 2nd postoperative days. After 80% hepatectomy, rats received either 30 kcal.kg-1.day-1 (group 1) or 200 kcal.kg-1.day-1 (group 2) of glucose for 48 h. In both rat groups, hepatic mitochondrial ATP synthesis 12 and 24 h after hepatectomy was accelerated when palmitic acid was used as the substrate and suppressed when pyruvate was used compared with sham-operated groups. This suggests that the energy substrate of the remnant liver was principally fatty acids rather than glucose, which seems to occur also in humans. Hepatic energy charge was within normal limits in group 1 (0.862 +/- 0.008) but decreased significantly in group 2 (0.818 +/- 0.006, p < 0.01) 12 h after hepatectomy. An abundance of glucose in the early postoperative period therefore caused a hepatic energy derangement by suppressing endogenous fat oxidation. This suppression was corroborated by the findings of lower immunoreactive glucagon and nonesterified fatty acid concentration in group 2. Therefore, glucose hyperalimentation in the early postoperative period after liver resection is not recommended.
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PMID:Fuel utilization and glucose hyperalimentation after liver resection. 781 53

We studied the distribution of the two enzymes involved in post-translational C-terminal alpha-amidation of regulatory peptides in rat digestive tract, using immunocytochemical methods and in situ hybridization techniques. The enzymes were located in most of the fibers and neurons of the myenteric and submucous plexus throughout the entire digestive tract and in endocrine cells of the stomach and colon. Staining of reverse-face serial sections demonstrated that the enzymes in endocrine cells of the stomach co-localized with gastrin in the bottom of the gastric glands. Some gastrin-immunoreactive cells near the neck of the gland were negative for PAM, suggesting that amidation takes place only in the more mature cells. In the colon all cells immunoreactive for glucagon and GLP1 were also positive for peptidylglycine alpha-hydroxylating monooxygenase (PHM) but not for peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). The absence of immunoreactivity for the amidating enzymes in endocrine cells of the small intestine, known to produce C-terminally amidated peptides, suggests the existence of other amidating enzymes.
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PMID:Localization of amidating enzymes (PAM) in rat gastrointestinal tract. 840 69

We tested the hypothesis that the metabolic changes in glucose, lipid, and protein metabolism seen during tumor necrosis factor (TNF) infusion were due to the increase in plasma glucagon concentration rather than to the direct effects of TNF. We employed a pancreatic clamp technique to keep plasma insulin and glucagon concentrations constant throughout a 4-h isotope infusion. Glucose, lipid, and protein kinetics were measured by means of the primed, constant infusion of [6,6-2H]glucose, [2H5]glycerol, [2H2]palmitic acid, and [1-13C]leucine. After a 2-h baseline period (period 1), TNF was infused as a primed, constant infusion (prime, 2.5 micrograms/kg; constant infusion, 62.5 ng.kg-1.min-1) for 2 h (period 2). Whereas plasma glucose concentration dropped significantly during TNF infusion, endogenous glucose production did not change. The decrease in glucose concentrations was due to a stimulation of glucose clearance (P < 0.05). The rate of lipolysis did not decrease significantly, but free fatty acid (FFA) flux and plasma FFA concentration significantly decreased during TNF infusion (P < 0.05). The rate of appearance of leucine was not affected by TNF infusion, but TNF caused a significant increase in 13CO2 excretion (P < 0.05) and leucine oxidation (P < 0.05). The calculated rates of whole body protein synthesis decreased. We concluded that TNF did not directly affect glucose production. Furthermore, changes in protein and lipid kinetics during TNF infusion were not mediated by changes in insulin or glucagon and may have reflected direct effects of TNF.
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PMID:TNF directly stimulates glucose uptake and leucine oxidation and inhibits FFA flux in conscious dogs. 896 76

IDX-1 (islet/duodenum homeobox-1) is a transcription factor expressed in the duodenum and pancreatic beta and delta cells. It is required for embryonic development of the pancreas and transactivates the Glut2, glucokinase, insulin, and somatostatin genes. Here we show that exposure of isolated rat pancreatic islets to palmitic acid induced a approximately 70% decrease in IDX-1 mRNA and protein expression as well as 40 and 65% decreases in the binding activity of IDX-1 for its cognate cis-regulatory elements of the Glut2 and insulin promoters, respectively. The inhibitory effect of palmitic acid required its mitochondrial oxidation since it was prevented by the carnitine palmitoyltransferase I inhibitor bromopalmitic acid. The palmitic acid effect on IDX-1 was correlated with decreases in GLUT2 and glucokinase expression of 40 and 25%, respectively, at both the mRNA and protein levels. Insulin and somatostatin mRNA expression was also decreased by 40 and 60%, whereas glucagon mRNA expression was not modified. After 48 h of exposure to fatty acids, total islet insulin, somatostatin, and glucagon contents were decreased by 85, 55, and 65%, respectively. At the same time, total hormone release was strongly stimulated (13-fold) for glucagon, whereas its was only marginally increased for insulin and somatostatin (1.5- and 1.7-fold, respectively). These results indicate that elevated fatty acid levels 1) negatively regulate Idx-1 expression; 2) decrease the expression of genes transactivated by IDX-1 such as those for GLUT2, glucokinase, insulin, and somatostatin; and 3) lead to an important increase in glucagon synthesis and secretion. Fatty acids thus have pleiotropic effects on pancreatic islet gene expression, and the negative control of Idx-1 expression may be an initial event in the development of these multiple defects.
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PMID:Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels. 937 11


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