Abnormal function and glucose metabolism in the type-2 diabetic db/db mouse heart.
This study examined cardiac function and glucose metabolism in the 6-month-old db/db mouse, a model of type-2 diabetes. Cine magnetic resonance spectroscopy (MRI) was used to measure cardiac function in vivo. The db/db mice had decreased heart rates (17%, p<0.01) and stroke volumes (21%, p<0.05) that resulted in lower cardiac output (35%, p<0.01) than controls. Although there was no difference in ejection fraction between the 2 groups, db/db mouse hearts had a 35% lower maximum rate of ejection (p<0.01) than controls. In a protocol designed to assess maximal insulin-independent glucose uptake, hearts were isolated and perfused in Langendorff mode and subjected to 0.75 mL.min(-1).(g wet mass)(-1) low flow ischemia for 32 min. Glucose uptake during ischemia was 21% lower than in controls, and post-ischemic recovery of cardiac function was decreased by 30% in db/db mouse hearts (p<0.05). Total cardiac GLUT 4 protein was 56% lower (p<0.01) in db/db mice than in controls. In summary, the db/db mouse has abnormal left ventricular function in vivo, with impaired glucose uptake during ischemia, leading to increased myocardial damage.
Panagia
Marcello
M
University Laboratory of Physiology, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Rd, OX1 3PT, Oxford, England.
Schneider
Jürgen E
JE
Brown
Ben
B
Cole
Mark A
MA
Clarke
Kieran
K
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D002302:Cardiac Output; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology*; D005227:Fatty Acids / Q000097:blood; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D007328:Insulin / Q000097:blood; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism*; D013318:Stroke Volume; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D007328:Insulin; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; D020155:3-Hydroxybutyric Acid