Chronic effects of type 2 diabetes mellitus on cardiac muscle contraction in the Goto-Kakizaki rat

Abstract

Type 2 diabetes mellitus accounts for more than 90% of all cases of diabetes mellitus, and cardiovascular complications are the major cause of mortality and death in diabetic patients. The chronic effects of type 2 diabetes mellitus on heart function have been investigated in the Goto-Kakizaki (GK) rat. Experiments were performed in GK rats and age-matched Wistar control rats at 18 months of age. The progressive effects of diabetes on glucose metabolism were monitored periodically by application of the glucose tolerance test. Ventricular action potentials were measured in isolated, perfused heart. Shortening and intracellular Ca(2+) were measured in electrically stimulated ventricular myocytes. The GK rats displayed mild fasting hyperglycaemia and progressively worsening glucose tolerance. At 18 months of age and 180 min after intraperitoneal injection of glucose (2 g (kg body weight)(-1)), blood glucose was 436 +/- 47 mg dl(-1) in GK rats compared with 153 +/- 18 mg dl(-1) in control animals. Heart weight to body weight ratio was significantly increased in GK rats (4.10 +/- 0.09 mg g(-1), n = 5) compared with control animals (3.36 +/- 0.22 mg g(-1), n = 4). Spontaneous heart rate was slightly reduced in GK rats compared with control rats. Although the amplitude of shortening was not altered, the amplitude of the Ca(2+) transient was significantly increased in myocytes from GK rats (0.78 +/- 0.11 ratio units) compared with control rats (0.50 +/- 0.06 ratio units). Despite progressively worsening glucose metabolism, at 18 months of age the contractile function of the heart appears to be well preserved.