Summary
Treatment with hydrochlorothiazide or furosemide does not impair the pancreatic function to increase insulin secretion in response to an elevation of blood glucose concentration. This has been shown in rats after single intravenous injection of 200 mg/kg as well as after oral application of 200 mg/kg and day of these diuretics over a period of 4 weeks. In contrast, 200 mg/kg diazoxide given intravenously causes a complete block of the glucose-inducible insulin secretion.
Cellular glucose uptake measured in the presence or absence of insulin has been found unaltered after administration of the diuretics or diazoxide.
Application of hydrochlorothiazide to alloxan diabetic rats results in a rise in blood glucose concentration which has not been observed in animals with unimpaired endocrine pancreatic function.
The increase in blood glucose concentration induced by the diuretic benzothiadiazine has been found related to an increase in glycogenolysis caused by an inhibition of 3′,5′-AMP phosphodiesterase in liver and skeletal muscle. The decreased breakdown in 3′,5′-AMP as a result of the inhibition of the phosphodiesterase increases the hyperglycemic effect of epinephrine.
Furosemide has been shown to decrease 3′,5′-AMP phosphodiesterase in liver but not in skeletal muscle of rats treated with 200 mg/kg of the diuretic. This is in accordance to an activation of liver glycogen-phosphorylase. The intensity of this enzymic activation, even in alloxan diabetic rats, does not suffice to result in a detectable rise in blood glucose. This may be explained by a compensatory uptake of glucose in skeletal muscle as application of furosemide does not lead to an accelerated glycogenolysis in this tissue reducing hexokinase activity by an increase in glucose-6-phosphate concentration. In these experiments the kidneys of the animals had been removed to avoid interference with changes in blood glucose concentration caused by an increase in catecholamine release in consequence of the diuretic effect leading to a reduction in extracellular fluid space. There is also no influence of furosemide on the hyperglycemic effect of epinephrine under the experimental conditions described.
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Ein Teil der Ergebnisse wurde auf der 7. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft vorgetragen (Schultz, Losert, Senft u.Sitt, 1966).
Wir danken der Deutschen Forschungsgemeinschaft für die Unterstützung unserer Untersuchungen.
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Senft, G., Losert, W., Schultz, G. et al. Ursachen der Störungen im Kohlenhydratstoffwechsel unter dem Einfluß sulfonamidierter Diuretica. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 255, 369–382 (1966). https://doi.org/10.1007/BF00593171
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DOI: https://doi.org/10.1007/BF00593171