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)

Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content. 2 Exposure to cadmium increases hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline- as well as glucagon-stimulated form(s) of adenylate cyclase. 3 In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load. 4 Zinc, when administered at the same time as cadmium, prevents the cadmium-induced lesions in both hepatic and pancreatic functions. 5 The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc.
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PMID:Prevention by zinc of cadmium-induced alterations in pancreatic and hepatic functions. 18 49

The effect of zinc ions on carbohydrate metabolism and intracellular Zn2+ was studied in hepatocytes from fed rats. The addition of ZnCl2 to the medium led to an almost 3-fold increase in lactate production and an increase in net glucose production of about 50%. Half-maximal rates occurred at about 40 microM ZnCl2. These effects were not seen with Mn2+, Co2+, or Ni2+ up to 80 microM, whereas Cu2+ at 80 microM and Cd2+ or Pb2+ at 8 microM exhibited similar effects as 80 microM ZnCl2. Changes in intracellular Zn2+ were followed by single cell epifluorescence using zinquin as a specific probe. Intracellular free Zn2+ in isolated hepatocytes was 1.26 +/- 0.27 microM, and the addition of ZnCl2 led to a concentration-dependent increase in epifluorescence. CdCl2 or PbCl2 at 8 microM was as potent as ZnCl2 at 20-80 microM, whereas NiCl2 at 80 microM was without effect. ZnCl2 completely abolished the inhibition of glycolysis by glucagon (cAMP). Glucagon led to a pronounced drop in cytosolic Zn2+. Both glucagon and zinc stimulated glycogenolysis by increasing the phosphorylation of glycogen phosphorylase but acted oppositely on glycolysis. Zinc overcame the inactivation of pyruvate kinase by glucagon without changing the hormone-induced protein phosphorylation. The antagonistic action of zinc and cAMP on glycolysis together with the rapid and marked decrease in free zinc concentration induced by glucagon (cAMP) may indicate an as yet unknown role of zinc as an important mediator of regulation of carbohydrate metabolism.
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PMID:Intracellular zinc movement and its effect on the carbohydrate metabolism of isolated rat hepatocytes. 856 42

Heme oxygenase-1 (HO-1) is the inducible form of the rate-limiting enzyme of heme degradation; it regulates the cellular content of heme. To investigate the role of the cAMP-dependent protein kinase (PKA) signaling pathway on hepatic HO-1 gene expression, primary rat hepatocyte cultures were treated with the PKA-stimulating agents dibutyryl-cAMP (Bt2cAMP), forskolin, and glucagon. HO-1 mRNA levels were induced by these agents in a time-dependent manner with a transient maximum after 6 hr of treatment. The induction of HO-1 was dose dependent, reaching a maximum at concentrations of 250 muM Bt2cAMP and 50 nM glucagon, respectively. The accumulation of HO-1 mRNA correlated with increased levels of HO-1 protein as determined by Western blot analysis. The Bt2cAMP-dependent induction of HO-1 mRNA expression was prevented by pretreatment with the PKA inhibitor KT5720 but not with the protein kinase G inhibitor KT5823. HO-1 mRNA induction by CdCl2 and heme was differentially affected by Bt2cAMP. Up-regulation of the HO-1 gene by Bt2cAMP occurred on the transcriptional level as determined by nuclear run-off assay and blocking of the Bt2cAMP-dependent induction of HO-1 mRNA by actinomycin D. Treatment with Bt2cAMP increased the half-life of HO-1 mRNA from 4.7 to 5.5 hr. Taken together, the results of the current study demonstrate that HO-1 gene expression is induced by activation of the cAMP signal transduction pathway via a transcriptional mechanism in primary rat hepatocyte cultures.
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PMID:The rat heme oxygenase-1 gene is transcriptionally induced via the protein kinase A signaling pathway in rat hepatocyte cultures. 949 15

In an attempt to establish a primate model of chronic cadmium (Cd) toxicosis, we ovariectomized cynomolgus monkeys and treated with CdCl2 by repeated intravenous injections for 13 to 15 months. The animals showed an increase in blood glucose from Month 10 and a decrease in blood insulin at Month 11of the Cd-treatment. Histopathological examination of the Cd-treated animals revealed islet atrophy with reduction in islet number and vacuolation of the islet cells, whereas there was no remarkable change in the acinar cells of the exocrine pancreas. In histomorphometrical examination, insulin-positive areas in the islets were significantly decreased, accompanying a relative increase of glucagon-positive areas. Large amounts of Cd accumulated in the pancreas, and metallothionein (MT), a Cd binding protein, was localized in the islets of Cd-treated animals. The present study demonstrated that the chronic intravenous injection of Cd to cynomolgus monkeys induced the accumulation of the metal in the pancreas, degeneration of islet B cells and the diabetic clinical signs. Therefore the islet B cell is one of the major targets of the chronic Cd poisoning in monkeys.
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PMID:Chronic cadmium treatment induces islet B cell injury in ovariectomized cynomolgus monkeys. 1267 53

In the present study, the effects of dexamethasone on cadmium-induced toxicity were evaluated in isolated rat hepatocytes. Hepatocytes were cultured for 24 h in William's E medium containing fetal calf serum (10%), insulin (0.1 IU/ml), and glucagon (0.01 microM) in the absence or presence of 0.1 microM dexamethasone. Cadmium chloride, 5 or 10 microM, was added to the medium and the toxicity was evaluated for up to 48 h after treatment. Lactate dehydrogenase (LDH) release, the reduced and oxidized glutathione ratio (GSH/GSSG), protein-SH groups, and lipid peroxidation levels were evaluated. Cadmium induced a dose- and time-dependent LDH release in control hepatocytes at 24 h (Cd 10 microM 42%) while hepatocytes pretreated with dexamethasone showed lower necrosis (Cd 10 microM 12% at 24 h). GSH/GSSH ratio and protein-SH groups were higher while lipid peroxidation was lower in dexamethasone-treated hepatocytes as compared with untreated cells. In conclusion, cadmium toxicity was associated with an increase in intracellular oxidative stress responsible for accelerated cell death. The use of dexamethasone prevented cadmium damage, suggesting that the cytoprotective action of this hormone is related to its effect in preventing changes in thiols such as glutathione and protein-SH groups.
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PMID:Dexamethasone protects cultured rat hepatocytes against cadmium toxicity: involvement of cellular thiols. 1999 67