Effects of GABAB agonists and antagonists on glycemia regulation in mice

MARIA M BONAVENTURA; MARTÍN CRIVELLO; MARÍA LAURA FERREYRA; MARTÍN REPETTO; CORA CYMERYNG; CARLOS LIBERTUN VICTORIA A. LUX-LANTOS; VICTORIA A. LUX-LANTOS

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Año: 2011

0014-2999

?×-Aminobutyric acid (GABA) has been proposed to inhibit insulin secretion through GABAB receptors (GABABRs) in pancreatic ?Ò-cells. We investigated whether GABABRs participated in the regulation of glucose homeostasis in vivo. BALB/c mice acutely pre-injected with the GABAB agonist baclofen presented glucose intolerance and diminished insulin secretion during a glucose tolerance test (GTT). The GABAB antagonist 2-hydroxysaclofen improved GTTs and reversed the effect of baclofen. Also a slight increase in insulin secretion was observed with 2-hydroxysaclofen. In chronically-treated animals both the agonist and the antagonist induced impaired GTTs; the antagonist, but not the agonist, also induced a decrease in insulin secretion. No alterations in insulin tolerance tests (ITT), weight or food intake were observed with the treatments. Due to its lipophylic characteristics baclofen can cross the blood brain barrier and could therefore exert central effects that may explain the impaired GTTs in the absence of effects on insulin secretion, such as alterations on the corticotropic axis regulation. Results demonstrate that GABABRs are involved in the regulation of glucose homeostasis in vivo. Treatment with agonists or antagonists, given acutely or chronically, altered glucose homeostasis and insulin secretion alerting to the need to evaluate glucose metabolism during the clinical use of these drugs.