Human amylin Transgenic mice show elevated Core Body temperature and Increased Energy Expenditure

Abstract

Introduction. Human amylin (hA), also called Islet Amyloid Polypeptide (IAPP) is a 37 amino acid protein that is co-secreted with insulin from the pancreatic islet β-cells upon stimulation with glucose (1,2). Aggregation of hA/IAPP into small soluble β-sheet-containing oligomers is linked to islet β-cell degeneration and the pathogenesis of type 2 diabetes (3). We have previously reported the characterisation of an hA/IAPP transgenic mouse line, which overexpresses human amylin in the pancreas and spontaneously develops diabetes (4). Amylin/IAPP reduces food intake after peripheral or central administration. It functions as both a short-term satiation signal and also has long-term anorectic and weight reducing actions. Studies have reported that amylin/IAPP may increase energy expenditure and increase body temperature, although the influence of amylin/IAPP on body temperature is still questionable. Purpose. This study sought to investigate whether there was a relationship between expression of the human amylin/IAPP protein, and metabolic and physiological parameters such as core body temperature, energy expenditure, weight, blood glucose and selected hormone levels in hA/IAPP transgenic mice. Methods. Blood Glucose, body weight, core body temperature were measured weekly and indirect calorimetry was performed in approximately 100 day old hA/IAPP transgenic and control littermates using the Comprehensive Laboratory Animal Monitoring System (CLAMS). Food intake, activity, O2 consumption (VO2), CO2 production (VCO2) were measured and respiratory quotients and energy expenditures were calculated. Serum hormone levels, including insulin, amylin, leptin and adiponectin, were measured in control and transgenic mice. Results and Conclusions. Weight, blood glucose levels, core body temperatures, food intake, activity, respiratory quotient (RQ) and energy expenditure results are presented along with serum hormone and liver glycogen levels in the hemizygous hA/IAPP transgenic mice, compared with their non-transgenic littermates. Hemizygous hA/IAPP transgenic mice had significantly higher core body temperatures and energy expenditure compared to their non-transgenic littermates, independent of the diabetic state of the transgenic animal. Adiponectin levels in serum were significantly lower and the liver contained increased glycogen content in the hemizygous hA/IAPP transgenic mice compared to their control littermates.