Rosane Gomez, Nelson Asnis, Seminamis L. Tannhauser and Helena M.T. Barros
(*)
Division of Pharmacology, Fundacao Faculdade Federal de Ciencia Medicas
de Porto Alegre - FFFCMPA, R. Sarmento Leite, 245, Porto Alegre, PC 90050
- 170, Brazil
(*) To whom correspondence should be addressed.
Abstract: 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.
Keywords: GABAA, GABAB, Hyperglycemia, Insulin