This study described the effects of GABA agonists on glucose plasma concentrations of streptozotocin-induced diabetic rats. Low doses of an indirect GABA agonist, AOAA (aminooxyacetic acid); a GABAA and a GABAB agent, THIP (4, 5, 6, 7-tetrahydroisoxazolo[5, 4-c]pyridone) and baclofen, respectively; and a benzodiazepine were administered to non-diabetic and to diabetic rats. Plasma glucose concentrations were estimated during fasting and after an oral glucose load. Diazepam (1 mg/kg), baclofen (1 mg/kg) and AOAA (30 mg/kg), significantly decreased glycemia after oral glucose overload of streptozotocin-induced diabetes. None of the GABA-acting agents tested changed fasting or glucose overload glycemia of normal rats. Diazepam was the only drug to increase the fasting blood glucose concentration of diabetic rats. Treatment with AOAA or diazepam was accompanied by increased insulin plasma concentrations in diabetic rats to levels similar to the ones of non-diabetic animals. These results demonstrate that benzodiazepines and other GABA drugs act the endocrine pancreas in vivo, ultimately increasing plasma insulin and decreasing high blood glucose levels of diabetic rats. The acute and prolonged effects of the multitude of drugs acting on the GABAA-benzodiazepine-chloride ionophore complex remain to be broadly investigated as a therapeutic tool in diabetes.
The Japanese Pharmacological Society 1999