Impact of age‐induced hyperglycaemia on structural remodelling in the left ventricle of the type 2 Goto‐Kakizaki rat

Abstract

Chronic hyperglycaemia (HG) induced by diabetes mellitus can elicit adverse structural remodelling in the heart. This study investigated the hypothesis whether pre‐diabetes and mild chronic HG in Goto‐Kakizaki (G‐K) type 2 diabetic rats can cause similar adverse remodelling of the heart. The study employed the left ventricles of 2 month (pre‐diabetes) and 18 month (mild chronic) old G‐K rats compared to age‐matched controls to investigate structural remodelling and associated changes transforming growth factor beta 1 (TGF‐beta1), brain natriuretic peptide (BNP), atrial natriuretic factor (ANP). pro‐hyperthropic markers Akt‐mTOR‐p70S6K1 and gene expressions for a number of extracellular matrix (EMC) factors which are associated with fibrosis. The results show that both groups of G‐K rats had moderate increases in blood fasting glucose compared to controls. They also had significantly (p<0.05) higher levels of blood glucose following GTT compared to controls confirming their diabetic status. G‐K rats had significantly (p<0.05) increased heart weights, heart weight to body weight ratio, left ventricle wall (LVW) to body weight ratio, LV free wall thickness and myocyte diameter compared to controls, an indication of marked hypertrophy. The changes were accompanied by significant (p<0.05) increases in TGF‐beta 1, BNP, ANP, Akt‐mTOR:p70S6K and gene expressions for ECM factors and their regulators in the left ventricles of G‐K rats compared to controls. The results reveal that both pre‐diabetes and mild chronic HG can evoke severe adverse remodelling of the LV.