Shift in metabolic substrate uptake by the heart during development of alloxan-induced diabetes.
Inhibition of endothelial nitric oxide (NO) synthase (eNOS) is associated with an increase in glucose uptake by the heart. We have already shown that Type I diabetes also causes a decrease in eNOS protein expression and altered NO control of both coronary vascular resistance and oxygen consumption. Therefore, we predict that the increase in plasma glucose and the reduction in eNOS during diabetes together would result in a large increase in cardiac glucose uptake. Arterial (A) and coronary sinus (C) plasma levels of glucose, free fatty acid (FFA), beta-hydroxybutyric acid (beta-HBA), and lactate were measured, and myocardial uptake was calculated before and at week 1, 2, 3, and 4 of alloxan-induced diabetes. The heart of healthy dogs consumed FFA (19.2 +/- 2.6 microeq/min) and lactate (19.7 +/- 3.4 micromol/min). Dogs in the late stage of diabetes (at week 4) had elevated arterial beta-HBA concentrations (1.6 +/- 0.7 micromol/l) that were accompanied by an increased beta-HBA uptake (0.3 +/- 0.2 micromol/min). In contrast, myocardial lactate (-4.8 +/- 3.0 micromol/min) and FFA uptake (2.5 +/- 1.9 microeq/min) were significantly reduced in diabetic animals. Despite a marked hyperglycemia (449 +/- 25 mg/dl), the heart did not take up glucose (-7.9 +/- 4.1 mg/dl). Our results indicate significant changes in the myocardial substrate utilization in dogs only in the late stage of diabetes, at a time when myocardial NO production is already decreased.
Linke
Axel
A
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Zhao
Gong
G
Recchia
Fabio A
FA
Williams
Jeffrey
J
Xu
Xiaobin
X
Hintze
Thomas H
TH
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000496:Alloxan; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D002245:Carbon Dioxide / Q000097:blood; D003243:Consciousness; D003326:Coronary Circulation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006863:Hydrogen-Ion Concentration; D007651:Keto Acids / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D012119:Respiration
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007651:Keto Acids; D009566:Nitrates; D009573:Nitrites; D002245:Carbon Dioxide; D019344:Lactic Acid; D000496:Alloxan; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen; D020155:3-Hydroxybutyric Acid