[Inhibitory effect of GABA on glucose- stimulated insulin secretion from isolated islets of langerhans in rat]

ABSTRACT

Gamma-amino butyric acid [GABA], an amino acid, present in some inhibitory neurons of the central nervous system, is also found in relatively high levels in the islets of Langerhans. Results of different studies concerning the effect of GABA on insulin secretion are controversial. The aim of this study was to determine the role of GABA and GABAB receptors on glucose-stimulated insulin secretion in isolated islets of rats. The collagenase digestion technique was used to isolate the islets from pancreata of 45 male Wistar rats [200-250g]. Insulin secretion was assessed in eight islets in each cup exposed to different concentrations of glucose [8.3 and 16.7 mM] in the presence or absence of GABA [25, 50, 100 micro M], baclofen [10, 20, 50 micro M] [GABAB agonist] and saclofen [50,100 micro M] [GABAB antagonist]. Insulin concentration was measured by the ELISA method. Insulin release was reported as mean +/- SEM micro U/isIet/50 min and p values of <0.05 were considered significant. GABA inhibited glucose [8.3 and 16.7 mM]-induced insulin secretion in isolated islets [P<0.05]. Different concentrations of baclofen had no significant effect on glucose-induced insulin secretion; however glucose [16.7 mM] stimulated insulin secretion in the presence of 100 micro M saclofen [91 +/- 8.8 micro U/islet/60 min] was significantly [p<0.05] higher compared to insulin secretion stimulated by 16.7 mM glucose alone [67.7 +/- 2.58 micro U/islet/60 min]. These findings indicate that GABA has an inhibitory effect on glucose-induced insulin secretion; and therefore it may play a regulatory role in insulin secretion. This effect needs to be taken in to account in the pathophysiology of diabetes