ABSTRACT
Diabetes mellitus and its complications is a serious global health problem and the total number of people with this disease is projected to rise from 171 million in 2000 to 366 million in 2030. A recent study among Emirati citizens reported age-standardized rates for diabetes mellitus [diagnosed and undiagnosed] and pre-diabetes in those 30-64 years old as 29.0% and 24.2%, respectively. The association between type 2 diabetes mellitus and obesity is very strong and cardiovascular disease is the leading cause of morbidity and mortality among diabetic patients. The changes in ventricular myocyte contraction, intracellular calcium and the expression of genes encoding cardiac muscle proteins that take place in young [9-13 weeks] and ageing [30-34 weeks] Zucker diabetic fatty [ZDF] rat heart have been reviewed. Diabetes mellitus was associated with a fourfold elevation in non-fasting blood glucose in young and ageing ZDF rat compared with age-matched Zucker lean controls. Amplitude of shortening was unaltered in myocytes from young and ageing ZDF rats. Time to peak and time to half relaxation of shortening was prolonged in myocytes from young ZDF rats and was unaltered in myocytes from ageing ZDF rats compared with controls. Amplitude of the Ca[2+] transient was unaltered in myocytes from young and ageing ZDF rats. Time to peak Ca[2+] transient was prolonged in myocytes from young and ageing ZDF rats. L-type Ca[2+] current was significantly reduced in myocytes from young and ageing ZDF rats. Sarcoplasmic reticulum Ca[2+] transport did not appear to be altered in myocytes from young or ageing ZDF rats. Expression of genes encoding L-type Ca[2+] channel proteins, plasma membrane transporters, sarcoplasmic reticulum Ca[2+] and regulatory proteins and cardiac muscle proteins were variously up-regulated, down-regulated or unaltered in ventricles from young and ageing ZDF rats. Up-regulated genes in young ZDF rat heart included CACNA[1C], CACNA1G, CACNA1H, ATP1A1 and MYH7, whereas down-regulated genes in young ZDF rat heart included ATP1B1, SLC9A1, ATP2A2, CALM1, MYH6, MYL2, ACTC1, TNNI3, TNNT2 and TNNC1. Up-regulated genes in ageing ZDF rat heart included CACNA1G, CACNA1H, ATP2A1 and MYL2, whereas down-regulated genes in ageing ZDF rat heart included CACNA2D3, SLC9A1, ATP2A2, MYH6 and TNNT2. Subtle changes in expression of genes encoding various cardiac muscle proteins may underlie functional changes in hearts of young and ageing ZDF rats compared with age-matched controls