Protein Restriction during Early Life in Rats Alters Pancreatic GABAA Receptor Subunit Expression and Glucagon Secretion in Adulthood

Abstract

ObjectiveGamma-aminobutyric acid (GABA) is present in the endocrine pancreas and contributes to insulin and glucagon secretion. Protein restriction during pregnancy and lactation causes impaired glucose homeostasis in adulthood. We investigated the effect of low protein (LP) diet on the GABAergic system within islets and associated changes in hormone release. MethodsWistar rats were fed control (C) or LP diet throughout gestation and lactation; all offspring received C diet from weaning (day 21). GABAA receptor presence in islets was examined by Western blot, and mRNA expression for glutamic acid decarboxylase (GAD) 65 and GABAA and GABAB receptor isoforms by real-time polymerase chain reaction at 130 days. Insulin and glucagon secretion were measured in vivo after L-arginine stimulation. ResultsL-glutamate, the precursor of GABA, was reduced in pancreas from offspring of LP-fed rats at birth. At day 21, animals receiving LP diet had an elevated GABAA presence within islets, lower fasting plasma insulin, and decreased islet insulin and glucagon content. By day 130, GABAA protein did not differ with diet, but the expression of GABAAβ3 subunit mRNA was decreased in the LP group. Glucagon secretion and gene expression were increased in LP-fed rats. Expression of GABAB and GAD within islets was unaltered. ConclusionsLP diet caused changes to GABAA receptor expression within islets with implications for glucagon secretion and glucose homeostasis.