Furosemide treatment causes age-dependent glucose intolerance and islet damage in obese-hyperglycaemic mice

The effects of furosemide on fasting serum glucose, glucose tolerance and pancreatic islet morphology were studied in ob/ob mice of two age groups, 3 months and 8 months. A single dose of furosemide (200 mg/kg body weight) induced acute hyperglycaemia in the young (3 months) as well as the old (8 months) ob/ob mice. Two days after the furosemide injection the glucose tolerance was markedly impaired in older animals, whereas it was normal in younger animals. Glucose tolerance in old mice varied markedly between individuals and showed two patterns. Thus, in one group of 8 months old mice, fasting serum glucose was elevated and glucose tolerance was very poor, whereas in the other group it was at least as good as in the saline-injected controls. Histological analysis showed normal islet morphology in furosemide-treatment young mice but an inflammatory reaction in islets from furosemide-injected old animals. A significant correlation between the degree of islet abnormality and glucose tolerance was observed. The data suggest that susceptibility to develop furosemide-induced long-term glucose intolerance is associated with the development of the obese-hyperglycaemic syndrome rather than being linked to the inheritance of the ob/ob genome as such.