Correspondence: S. Zahediasl, PhD, Professor of Endocrine Physiology, Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box: 19395-4763, Tehran, Iran. Tel: +98 21 22432500. Fax: +98 21 22402463. E-mail: zahedi@endocrine.ac.ir (Received 28 November 2010; accepted 21 April 2011) ORIGINAL ARTICLE Time-dependent effect of GABA on glucose-stimulated insulin secretion from isolated islets in rat FARZANEH FARAJI 1 , ASGHAR GHASEMI 1 , FERESHTEH MOTAMEDI 2 & SALEH ZAHEDIASL 1 1 Endocrine Research Center, Research Institute for Endocrine Sciences and 2 Neurosciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Abstract Objective. Gamma-amino butyric acid (GABA) is an inhibitory neurotransmitter found widely in the central nervous system and some peripheral tissues such as the islets of pancreas. The aim of this study was to determine the time depend- ency of the effect of GABA on glucose-stimulated insulin secretion in isolated islets of rats. Materials and Methods. The collagenase digestion technique was used to isolate the islets from pancreata of male Wistar rats (200–250 g). Insulin secre- tion was assessed in islets exposed to different concentrations of glucose (8.3 and 16.7 mM), in the presence or absence of GABA (50 μM), for different incubation times and also pre-incubation of islets with GABA, 30 and 45 min before 8.3 mM glucose stimulation. Furthermore insulin secretion with different concentrations of glucose (8.3 and 16.7 mM), and in the presence or absence of different concentrations of baclofen, a GABA B agonist and of saclofen, a GABA B antagonist during 1 h of incubation was assessed. Insulin release was reported as mean  SE μU/islet/min and p values of 0.05 were considered significant. Results. GABA with concentration of 50 μM inhibited the glucose stimulated insulin secretion during a 60 min incubation period. Baclofen had no significant effect on glucose-induced insulin secretion, while saclofen (100 μM) significantly increased 16.7 mM glucose-induced insulin secretion in 60 min of incubation ( p  0.05). Pre-incuba- tion of islets with GABA for 45 min, before glucose stimulation, increased glucose-induced insulin secretion. Conclusion. GABA could have both stimulatory and inhibitory effects on glucose-stimulated insulin secretion, depending on the time of exposure and glucose concentration. Key Words: GABA, insulin, islets, rats Introduction It has been demonstrated that gamma amino butyric acid (GABA), as an inhibitory neurotransmitter in the nervous system, is also found in the pancreas [1,2], and may play a critical role in islet cell viability and function [3]. It suppresses apoptosis, acts as a mitogen in B cells and delays the onset of diabetes in animal models [4]. The excitatory and inhibitory effects of GABA on glucose-induced insulin secretion have been reported [5–8]. Some studies have shown the different effects of GABA on pancreatic isolated islets with different incubation times. Ligon et al. reported that GABA could increase the rate of islet cell proliferation during and following 60 min exposure to GABA [3]. In addi- tion, islet insulin content exposed to GABA during the first hour of culture was significantly increased [3]. Pretreatment of islets with GABA and GABA B R ago- nists (baclofen) in culture medium for 1h enhances glucose-induced insulin secretion. On the other hand, perfusion of the isolated dog pancreas with GABA, dose dependently decreases glucose and arginine-induced insulin secretion [7]. GABA in concert with glucose plays a role in the regulation of insulin secretion [9]. Dong et al., showed that GABA, in the presence or absence of glucose in INS-1, has excitatory or inhibitory effects on insulin secretion respectively [9]. It appears that the effect of GABA on islets function is not well established and, to the best of our knowl- edge, no study has addressed the issue of the role of time and glucose on the effect of GABA on insulin secretion on isolated islets. This study was designed to assess the effect of the time of exposure of GABA Scandinavian Journal of Clinical & Laboratory Investigation, 2011; Early Online, 1–5 ISSN 0036-5513 print/ISSN 1502-7686 online © 2011 Informa Healthcare DOI: 10.3109/00365513.2011.586131 Scand J Clin Lab Invest Downloaded from informahealthcare.com by 93.110.3.222 on 05/31/11 For personal use only.