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)

There are several situations in which medical therapy of hyperinsulinism induced by islet cell tumors or hyperplasia is necessary and at present we have at our disposal several drugs which are capable of reducing endogenous hyperinsulinism. They are: -Streptozotocin, which represents today the most useful therapeutic agent for beta cell carcinoma therapy; -Diazoxide, which represents the drug of first choice for the treatment of most hypoglycemic syndromes caused by islet cell adenoma or hyperplasia; -Propranolol, Chlorpromazine, Diphenylhydantoin, which may be regarded as a useful alternative to diazoxide, although they are capable of giving rather inconstant results. These drugs may today effectively substitute for corticosteroids and glucagon in the medical treatment of almost every chronic hyperinsulinemic hypoglycemic syndrome, including malignant beta cell carcinoma.
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PMID:Medical treatment of endogenous organic hyperinsulinism. 17 29

Acetaminophen hepatotoxicity has been shown previously to be potentiated by fasting, and the mechanism of hepatotoxicity has been correlated with depletion of reduced glutathione and the resulting elevation of cytosolic calcium. Chlorpromazine inhibited the hepatotoxicity of acetaminophen in a dose-dependent manner in fed and fasted mice. A 6 mg/kg dose of chlorpromazine prevented the acetaminophen-promoted increase in SGPT levels and prevented hepatic necrosis. Chlorpromazine did not prevent the depletion of reduced glutathione by acetaminophen in fed or fasted mice, although it did decrease the extent of reduced glutathione depletion caused by acetaminophen in fed mice from 80% depletion to 67% depletion. We propose that chlorpromazine causes a negative sensitivity modulation to calcium in hepatocytes, as evidenced by chlorpromazine preventing the acetaminophen-stimulated rise in phosphorylase a activity. We also propose that fasting potentiates acetaminophen hepatotoxicity by causing a positive sensitivity modulation to calcium in hepatocytes via the actions of glucagon.
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PMID:Inhibition of acetaminophen hepatotoxicity by chlorpromazine in fed and fasted mice. 339 Feb 8

Chlorpromazine (3 x 10(-4)M) prevents the stimulation of adenyl cyclase activity in thyroid membranes produced by thyrotropin and prostaglandin, ACTH stimulation of adenyl cyclase in adrenal tissue, and glucagon- and epinephrine-stimulation of adenyl cyclase activity in liver. Baseline activity is unaffected. Parathyroid hormone stimulation of kidney preparations was not inhibited under these conditions. At chlorpromazine concentrations >3 x 10(-4)M F(-)-stimulated cyclase activity of thyroid and adrenal tissue was increased. Other phenothiazines, trifluoperazine, and prochlorperazine, have similar effects on thyrotropin and F(-)-stimulated cyclase activity of thyroid. Na(+)- K(+)-dependent ATPase of thyroid is also inhibited by chlorpromazine. Since thymol causes a similar dissociation of hormone- and F(-)-stimulated adenyl cyclase, it is concluded that the surface properties of these agents best account for their effects on adenyl cyclase.
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PMID:Inhibition of hormone-sensitive adenyl cyclase by phenothiazines. 431

Glucagon enhances the electrical activity of pancreatic beta-cells. The mechanism of the glucagon-evoked enhancement of electrical activity was investigated in terms of glucose metabolism. ICR mice aged 6-12 weeks were used for experiments. Intracellular Ca2+ increased in parallel with the enhancement of electrical activity. The stimulating effect of glucagon on Ca2+ oscillation was suppressed by calmodulin-antagonists (Chlorpromazine, W-7, and trifluoperazine). To trace the glucagon-evoked change in glucose metabolism, the reduced pyridine nucleotide (NAD(P)H) fluorescence was monitored using the microfluorometry with the excitation of 360 nm and the emission of 465 nm in islet cell clusters mainly consisting of beta-cells. In the presence of 2.5 mM Ca2+ glucagon (8.6 X 10(-8) M) increased the NAD(P)H fluorescence, while in the absence of Ca2+ the hormone had no effect on the fluorescence. Extracellular Ca2+ removal from the glucagon-containing perifusion solution decreased the fluorescence to the level which had been attained before glucagon was added. Chlorpromazine (10 microM) reversed the glucagon-induced increase of NAD(P)H fluorescence as well as removing Ca2+ W-7 (15 microM) and trifluoperazine (30 microM) also suppressed the glucagon-induced increase of NAD(P)H. These results suggest that Ca2+/calmodulin system is involved in the acceleration of glycogenolysis by glucagon in beta-cells. On the basis of these observations, the mechanism of glucagon-induced enhancement of electrical activity and the relative ineffectiveness of glucagon at low glucose concentrations were discussed.
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PMID:Glucagon induces Ca2+-dependent increase of reduced pyridine nucleotides in mouse pancreatic beta-cells. 859 11