Diuretics and carbohydrate metabolism: The effects of furosemide and amiloride on blood glucose, plasma insulin and cations in the rat

Abstract

The effects of two unrelated diuretics, furosemido and amiloride on blood glucose, plasma insulin and glucose tolerance in the consCious rat are reported. Furosemide (1 mg/kg or 2 mg/kg) given intravenously caused an immediate but highly transient 23% and 53% fall in plasma insulin followed by a rise in blood glucose. The hyperglycaemic effect alone occurred in mild streptozotocin diabetic animals. Furosemide given with or 30 rain before intravenous glucose (0.5 G/kg) caused glucose intolerance with diminished insulin response. None of these effects were observed in adrenalectomised animals. Amiloride (1, 5 or 10 mg/kg) given I.V. alone immediately increased plasma insulin (up to 213 FU/ml) without affecting blood glucose. This effect was attenuated by mild streptozotocin diabetes. Amiloride given with or 30 min before glucose increased the insulin area without affecting glucose disappearance. Chronic administration enhanced glucose disappearance with increased plasma insulin re~aponsc, and caused hyperkalaemia. Chronic furosomide administration had no effects. Possible mechanisms for these effects are discussed.

Probenecid potentiates the hyperglycaemic effect but reduces the diuretic effect of frusemide in mice

“…The present results are in accord with previous work on small rodents (Wales et al, 1968;Foy & Furman, 1971;Aynsley-Green & Alberti, 1973;Wexler, 1981) in showing that frusemide induces acute hyperglycaemia in mice. It has been proposed that this hyperglycaemia is a secondary effect of the diuresis produced by alterations in the electrolyte balance (Aynsley-Green & Alberti, 1973) or reflex-mediated catecholamine release (Foy & Furman, 1973;AynsleyGreen & Alberti, 1973).…”

“…It has been proposed that this hyperglycaemia is a secondary effect of the diuresis produced by alterations in the electrolyte balance (Aynsley-Green & Alberti, 1973) or reflex-mediated catecholamine release (Foy & Furman, 1973;AynsleyGreen & Alberti, 1973). As direct experimental evidence in support of this general idea, Foy & Furman (1973) showed that removal of the kidneys in mice prevented the hyperglycaemia.…”

“…The early investigations by Senft (1966) showed that neither single-dose nor long-term administration of frusemide (200 mg kg-' body weight) to rats affected serum glucose or serum insulin levels. Later studies have indicated that single-dose administration to mice (Foy & Furman, 1971) or rats (Wales et al, 1968;Aynsley-Green & Alberti, 1973;Wexler, 1981) can elicit a transient hyperglycaemia. The precise reasons for the diabetogenic action in laboratory animals are unclear, although several mechanisms have been proposed.…”

“…The precise reasons for the diabetogenic action in laboratory animals are unclear, although several mechanisms have been proposed. Thus it has been suggested that hyperglycaemia occurs secondary to renal effects; diuresisinduced hypotension could result in the release of catecholamines followed by glycogenolysis (Aynsley- Green & Alberti, 1973;Foy & Furman, 1973). An alternative suggestion is that diuresis-induced disturbances of serum electrolyte concentration may cause the change in carbohydrate metabolism (AynsleyGreen & Alberti, 1973).…”

Furosemide Treatment Causes Age‐Dependent Glucose Intolerance and Islet Damage in Obese‐Hyperglycaemic Mice

“…Furosemide causes disturbed carbohydrate metabolism also in laboratory animals (Foy 1967;Wales et a/. 1968;Aynsley-Green & Alberti 1973;Foy & Furman 1971, 1972Sandstrom 1987;Sandstrom & Sehlin 1988a &. b).…”