Effect of diuretics on mouse blood sugar following single dose administration

Abstract

Summary Frusemide, in doses which were maximal or supramaximal in respect of its natriuretic, diuretic and kaliuretic properties, produced a dose dependent, transient hyperglycaemic response in the mouse. Bilateral nephrectomy resulted in a complete abolition of the hyperglycaemic response. The hyperglycaemic response was accompanied by a decrease in liver glycogen and was significantly attenuated by adrenalectomy, adrenal demedullation and pretreatment with dihydroergotamine (DHE). In the nephrectomized mouse frusemide treatment produced a marked reduction in intravenous glucose tolerance and a reduction in the plasma concentration of immunoreactive insulin following glucose administration. The drug had no detectable effect upon insulin sensitivity. Hydrochlorothiazide exerted no detectable effect on mouse blood sugar. Ethacrynic acid hyperglycaemia was obtainable after intraperitoneal or intramuscular injection, but not after intravenous injection. Intravenously administered ethacrynic acid exerted no effect upon intravenous glucose tolerance or insulin sensitivity in the nephrectomized mouse.

Effect of single dose administration of diuretics on the blood sugar of alloxan‐diabetic mice or mice made hyperglycaemic by the acute administration of diazoxide

“…Frusemide hyperglycaemia has been shown to depend upon the presence of the kidneys, although the impairment of intravenous glucose tolerance produced by the drug in the nephrectomized mouse suggests the involvement of some extra-renal component (Foy & Furman, 1971). The results presented in this paper appear to confirm the role of the kidneys in the production of hyperglycaemia by frusemide.…”

“…However, Foy & Furman (1971) suggested that this impairment of glucose tolerance produced by frusemide was mediated by a reduction in the plasma insulin levels following glucose administration. Alloxan-diabetes and diazoxide treatment are associated respectively with an absence of and a decrease in the elevation of plasma insulin in response to glucose.…”

“…In view of the demonstrated impairment of intravenous glucose tolerance produced by frusemide in the nephrectomized mouse (Foy & Furman, 1971), it is perhaps surprising that the drug did not influence the hyperglycaemia produced by alloxan or diazoxide under these conditions. However, Foy & Furman (1971) suggested that this impairment of glucose tolerance produced by frusemide was mediated by a reduction in the plasma insulin levels following glucose administration.…”

“…Glycogenolysis, produced by catecholamines liberated from the adrenal medulla in response to volume depletion, together with haemoconcentration, would contribute towards the hyperglycaemia, the excess blood sugar being assimilated inadequately in the alloxan-diabetic animal. In this context it is interesting that a submaximal diuretic dose of frusemide (25 mg/kg; Foy & Furman, 1971) produced marked hyperglycaemia in alloxan-diabetic mice but not in normal or diazoxide-treated animals. The abolition by nephrectomy of the hyperglycaemic responses to ethacrynic acid and frusemide in the alloxan-diabetic mouse would support the above ideas.…”

“…In a previous report (Foy & Furman, 1971) it was shown that frusemide, but not hydrochlorothiazide, could produce hyperglycaemia in the mouse following the acute administration of large doses. Ethacrynic acid produced a hyperglycaemia that was shown to depend upon the route of administration and which was probably attributable to the irritant effects of the drug solutions.…”