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)

In chronic glucagon-treated ducklings (GT) showing thermogenic and hyperthermic responses without shivering to glucagon test injection and in control ducklings (TN; both aged 44 +/- 1 days and reared at thermoneutrality), subsarcolemmal (S) and intermyofibrillar (I) mitochondria from gastrocnemius muscle and mitochondria from liver were isolated. Respiration and cytochrome oxidase activity were determined in these isolated mitochondria by polarography and creatine kinase activity by spectrophotometry, both at 25 degrees C. In GT ducklings, the powerful thermogenesis observed in vivo after a glucagon test injection may be due to the uncoupling effect of released free fatty acids (FFA) in loose-coupled mitochondria because their respiration increased as a function of FFA concentration, and the loose coupling of these mitochondria was reversed by addition of albumin. In all types of mitochondria from GT ducklings, the increase in respiration because of FFA was about double that in mitochondria from controls. There was no change in creatine kinase activity from liver and I mitochondria, but a 16% decrease in this enzyme activity (expressed per mg mitochondrial protein) from S mitochondria was shown despite a strong increase in cytochrome oxidase activity from liver mitochondria (+114% if expressed per g tissue) and from muscle mitochondria (I, +53 or +48%; S, +41 or +97% if expressed per mg mitochondrial protein or per g tissue, respectively). These results support a coupling defect in liver and skeletal muscle mitochondria from the GT hyperthermic ducklings and an uncoupling reinforcement by FFA.
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PMID:Loose-coupled mitochondria in chronic glucagon-treated hyperthermic ducklings. 254 12

Glucagon has been shown to increase further the enhanced tolerance for hypoxia of mice with elevated blood ketones and to stimulate ketone utilization by rat brain slices, suggesting that glucagon may affect brain metabolism. In addition to stimulating gluconeogenesis, glucagon alters the metabolism of mitochondria isolated from liver and heart. This study was designed to test whether glucagon can act directly and selectively on brain mitochondrial substrate oxidation. Mitochondria were isolated from normal murine brains using differential centrifugation through Ficoll gradients. Glucagon (3.6 microM) stimulated respiration in the presence of glutamate, and glutamate plus beta-hydroxybutyrate, but not in the presence of glutamate plus malate, succinate or beta-hydroxybutyrate alone. With glutamate as the substrate the hormone significantly increased State 3 oxygen consumption rates from control values of 91 mol O2/mol of cytochrome aa3/min to 117 mols O2/mol/aa2/min (p less than 0.0001), and also increased State 4 rates slightly but significantly. Glucagon did not change mitochondrial respiratory control ratios, but increased estimated rates of ATP synthesis from 434 (control) to 597 mols ADP consumed/mol aa3/min (p less than 0.0001). The data indicate that in vitro glucagon has a direct and substrate-specific stimulatory effect on isolated brain mitochondria. These substrate-specific effects were not altered when respiration was studied in the presence of postmitochondrial supernatant or exogenous 3',5'-cyclic AMP, indicating that glucagon, in addition to an in vivo action via activation of membrane-bound adenylate cyclase, can act, at least in vitro, directly and selectively on brain mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substrate-specific stimulation by glucagon of isolated murine brain mitochondrial oxidative phosphorylation. 300 83

Despite long-standing observations of a whole-body thermogenic effect of glucagon, the role of glucagon in activating thermogenesis in brown adipose tissue has not often been studied. We investigated the ability of administered glucagon to produce alterations in brown adipose tissue similar to changes produced by accepted stimuli of brown fat activity: cold, norepinephrine, and overfeeding. Eighteen days of glucagon injections (1 mg/kg) to male Sprague-Dawley rats produced, relative to saline-injected controls, decreases in feed efficiency and increases in brown adipose tissue weight, protein content, DNA content, and mitochondrial mass as reflected in cytochrome oxidase activity. The observed changes were similar, though of lesser magnitude, to changes produced in these same parameters induced by administration of norepinephrine (250 micrograms/kg) for a positive control group. Four days of glucagon administration (1 mg/kg) produced increases in specific activity of cytochrome oxidase and lipoprotein lipase. After 8 days of glucagon administration, changes in whole-pad activity similar to those seen with 18 days of administration were present. Glucagon also increased whole-pad lipoprotein lipase activity after 4 and 8 days. Surgically denervated interscapular brown adipose tissue retained its ability to respond to exogenous glucagon, though the magnitude of the response was diminished. Guanosine 5'-diphosphate (GDP) binding to brown adipose tissue mitochondria was measured as an assessment of functional state after 5 days of glucagon (1 mg/kg). There was an increase in GDP binding relative to controls whether expressed as picomoles per milligram mitochondrial protein or nanomoles per pad.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucagon stimulation of brown adipose tissue growth and thermogenesis. 302 65

Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.
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PMID:Altered muscle energy metabolism in post-absorptive patients with chronic renal failure. 924 94

A three-step biotin-anti-biotin gold-detection system (method A) has been applied for ultraimmunocytochemistry using ultrasmall colloidal gold (0.8 nm) linked to anti-biotin antibodies which were visualized and enhanced by silver reduction. The reactivity for glucagon in human pancreatic islets and for cytochrome-c oxidase in heart mitochondria has been compared to a two-step ultrasmall immunogold technique (method B). For both antigens, method A provided significantly higher labelling indices (P<0.001): the labelling density for cytochrome-c oxidase was 223/microm2 using method A and 78/microm2 using method B. For glucagon, the labelling density was 1455/microm2 with method A and 322/microm2 with method B. The results demonstrate that the silver-intensified biotin-anti-biotin gold-detection system is a valuable immunocytochemical method for signal enhancement. The method utilizes biotinylated antibodies from different species, allowing its broad application at the electron microscopic level.
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PMID:The application of a biotin-anti-biotin gold technique providing a significant signal intensification in electron microscopic immunocytochemistry: a comparison with the ultrasmall immunogold silver staining procedure. 950 72

Glucagon promotes hepatic glucose production maintaining glucose homeostasis in the fasting state. Glucagon maintains at high level in both diabetic animals and human, contributing to hyperglycemia. Mitochondria, a major place for glucose oxidation, are dysfunctional in diabetic condition. However, whether hepatic mitochondrial function can be affected by glucagon remains unknown. Recently, we reported that FOXO1 is an important mediator in glucagon signaling in control of glucose homeostasis. In this study, we further assessed the role of FOXO1 in the action of glucagon in the regulation of hepatic mitochondrial function. We found that glucagon decreased the heme production in a FOXO1-dependent manner, suppressed heme-dependent complex III (UQCRC1) and complex IV (MT-CO1) and inhibited hepatic mitochondrial function. However, the suppression of mitochondrial function by glucagon was largely rescued by deleting the Foxo1 gene in hepatocytes. Glucagon tends to reduce hepatic mitochondrial biogenesis by attenuating the expression of NRF1, TFAM and MFN2, which is mediated by FOXO1. In db/db mice, we found that hepatic mitochondrial function was suppressed and expression levels of UQCRC1, MT-CO1, NRF1 and TFAM were downregulated in the liver. These findings suggest that hepatic mitochondrial function can be impaired when hyperglucagonemia occurs in the patients with diabetes mellitus, resulting in organ failure.
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PMID:Glucagon regulates hepatic mitochondrial function and biogenesis through FOXO1. 3102 11