People affected by diabetes are at an increased risk of developing
heart failure than their non-diabetic counterparts, attributed in part to a distinct cardiac pathology termed
diabetic cardiomyopathy.
Mitochondrial dysfunction and excess
reactive oxygen species (ROS) have been implicated in a range of
diabetic complications and are a common feature of the diabetic heart. In this study, we sought to characterise impairments in mitochondrial structure and function in a recently described experimental mouse model of
diabetic cardiomyopathy. Diabetes was induced in 6-week-old male FVB/N mice by the combination of three consecutive-daily
injections of low-dose
streptozotocin (STZ, each 55 mg/kg i.p.) and high-fat diet (42% fat from
lipids) for 26 weeks. At study end, diabetic mice exhibited elevated
blood glucose levels and
impaired glucose tolerance, together with increases in both
body weight gain and fat mass, replicating several aspects of human
type 2 diabetes. The myocardial phenotype of diabetic mice included increased myocardial
fibrosis and left ventricular (
LV) diastolic dysfunction. Elevated LV
superoxide levels were also evident. Diabetic mice exhibited a spectrum of LV mitochondrial changes, including decreased mitochondria area, increased levels of mitochondrial
complex-III and
complex-V protein abundance, and reduced complex-II oxygen consumption. In conclusion, these data suggest that the low-dose STZ-high fat experimental model replicates some of the mitochondrial changes seen in diabetes, and as such, this model may be useful to study treatments that target the mitochondria in diabetes.