Age‐dependant structural remodelling in the left ventricle of type 2 diabetic Goto‐Kakizaki rat

Abstract

Long term hyperglycaemia (HG) elicits adverse structural remodelling of the heart. This study tests the hypothesis that both pre-diabetes (2 months) and mild chronic (18 months) HG in G-K type 2 diabetic rats can cause similar adverse remodelling of the heart. This study employed isolated left ventricles of G-K rats compared to age-matched Wistar controls to investigate structural remodelling and associated changes in transforming growth factor beta 1 (TGF-β1), brain natriuretic peptide (BNP), atrial natriuretic factor (ANP), pro-hypertrophic markers; Akt-mTOR-p70S6K1 and gene expressions for several extracellular matrix (ECM) factors associated with fibrosis. Diabetes was confirmed using the fasting blood glucose (FBG) and glucose tolerance test (GTT). Results for both groups of G-K rats indicate moderate increases in FBG and significantly (p<0.05) higher levels of blood glucose following GTT compared to controls confirming diabetic status. No significant differences in body weights were identified, 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 Wistar controls, an indication of marked hypertrophy of the heart. These changes were accompanied by significant (p<0.05) increases in TGF-beta1, BNP, ANP, Akt-mTOR-p70S6K and gene expressions for ECM factors and regulators in the left ventricles of G-K rats compared to Wistar controls. Results reveal both pre-diabetes and mild chronic HG to be detrimental to cardiac structure and function leading to severe adverse remodelling of the LV.