Insights into the cardiovascular complications of a novel mouse model of Diabetes Mellitus: a mechanistic view

Abstract

Heart failure (HF) is one of the commonest complications of Diabetes Mellitus(DM) with the prevalence of DM reported at around 30% in many pivotal heartfailure studies. However the pathophysiological mechanisms that contribute toHF development in diabetes are poorly understood. To investigate this we useda novel human relevant mouse model of DM (GENA348) in which there is apoint mutation in the glucokinase (Gck) gene, the glucose sensor whichregulates insulin secretion. A mutation in the same gene is known to underlieMaturity Onset Diabetes of the Young Type 2 (MODY 2) in humans. The mutantmice developed significant hyperglycaemia with normal insulin levels due to thealtered glucose sensing. We examined the molecular mechanisms thatcontribute to the HF phenotype in DM.Mean random blood glucose was found to be increased in the GENA348 mutant(HO) mice compared to wild type (WT) littermates (WT 6.9±0.3mmol/L vs HO20.6±0.8mmol/L, P

Date of Award	1 Aug 2012
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Mamas Mamas (Supervisor) & Elizabeth Cartwright (Supervisor)