Effect of Glucolipotoxicity upon Pancreatic β-cell Function: Role of Transglutaminase 2
Bernadette F. Walsh
School of Science & Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS
15th April 2014
Abstract
Type 2 Diabetes Mellitus is characterised by chronic hyperglycaemia and hyperlipidaemia which contributes to progressive pancreatic islet β-cell failure and insulin resistance. The disorder is often associated to obese individuals with diets high in saturated fats. The combination of high blood glucose and non-esterified free fatty acids contributes to glucolipotoxicity, which has downstream effects on β-cell function, glucose metabolism and insulin sufficiency. This study investigates the role of transglutaminase 2, which is a ubiquitous and multi-functional enzyme. The aim of this investigation is to study the effect of glucolipotoxicity upon pancreatic β-cell transglutaminase 2 expression in order to assess its role in type 2 diabetes mellitus. The methods involved the preparation of rat insulinoma-1 cell line culture and western blotting to compare transglutaminase expression between a bovine serum albumin control and fatty acid/glucose treated extracts. The results exhibited an up-regulation of transglutaminase 2, with three lysate replicates (n=3). With densitometry quantification, an average fold change of 2.90 was detected, between the control and glucolipotoxicity bands. The results were proved as statistically significant at 95% confidence interval (p=<0.05) with a t-test value of 0.0178. In conclusion, glucolipotoxicity caused an up-regulation of transglutaminase 2, which provides a link between this protein and type 2 diabetes mellitus.
Key words:
Type 2 diabetes mellitus, pancreatic β-cell, pancreatic islets, β-cell dysfunction, glucolipotoxicity, transglutaminase, INS-1, glucose stimulated insulin secretion, western blotting.