Islet transplantation improves glucose oxidation and mechanical function in diabetic rat hearts.
In poorly controlled diabetes an impairment of glucose use can contribute to a depression in mechanical function of rat hearts. In this study we determined the effects of islet transplantation on glucose use and heart function in streptozotocin-induced diabetic rats. Myocardial function, glycolysis, and glucose oxidation were measured in isolated working hearts obtained from control, diabetic, and islet-transplanted diabetic Wistar-Furth rats. Islets (1200) were transplanted beneath the kidney capsule 2 weeks after a single i.v. dose of streptozotocin (55 mg/kg). The study consisted of three groups: (i) islet-transplanted diabetic rats, (ii) untreated diabetic controls, and (iii) normal controls. Following 11 weeks of monitoring, working hearts were perfused at a 11.5-mmHg (1 mmHg = 133.3 Pa) preload and 80-mmHg afterload, with buffer containing 11 mM [5-3H,14C(U)]glucose, 1.2 mM palmitate, and 100 microU/mL insulin. In untreated diabetic rat hearts, glucose oxidation rates were markedly depressed compared with control hearts (30.4 +/- 4 and 510 +/- 68 nmol.g-1 dry wt..min-1, respectively). Low glucose oxidation rates in diabetic rats were significantly improved in islet-transplanted animals (234 +/- 39 nmol.g-1 dry wt..min-1). The low glucose oxidation rates in untreated diabetic rat hearts were accompanied by an impaired mechanical function compared with control hearts, which was improved by islet transplantation (heart rate x developed pressure x 10(-3) was 10.6 +/- 0.9, 14.8 +/- 1.3, and 14.8 +/- 1.5 beats.mmHg.min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Lopaschuk
G D
GD
Cardiovascular Disease Research Group, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Lakey
J R
JR
Barr
R
R
Wambolt
R
R
Thomson
A B
AB
Clandinin
M T
MT
Rajotte
R V
RV
D000332:Aerobiosis; D000818:Animals; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006019:Glycolysis / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D011920:Rats, Inbred WF
D005947:Glucose