Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine

William C. Stanley, Jennifer L. Hall, Kevin R. Smith, Gregory D. Cartee, Timothy A. Hacker, Judith A. Wisneski

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 ± 2.1 v 6.6 ± .5 mmol/L), and had lower fasting insulin levels (27 ± 8 v 79 ± 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with d-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 ± .10 to 0.43 ± .08 mL · g-1 · min-1 in the nondiabetic group, and from 1.30 ± .15 to 0.55 ± .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies. Diabetes resulted in significantly lower GLUT 4 levels in both the subepicardial and subendocardial layers (23% [P < .01] and 11% [P < .05], respectively). There were no subepicardial/subendocardial differences in GLUT 4 levels in either group. In conclusion, 1 month of streptozocin diabetes resulted in a modest decrease in myocardial GLUT 4 levels, but did not affect the rate of glycolysis during myocardial ischemia.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalMetabolism
Volume43
Issue number1
DOIs
StatePublished - Jan 1994

Bibliographical note

Funding Information:
From the Biodynamics Laboratoy and the Section of Cardioloa, University of Wisconsin, Madtion, WI; the Department of Medicine, University of California, San Francisco; and the Veterans Affairs Medical Center, San Francisco. CA. Submitted September 28, 1992; accepted February I, 1993. Supported by the University of Wisconsin Graduate School, the American Hean Association-Wisconsin Ajiliute (W. C.S.), the Juvenile Diabetes Foundation International (W. C.S.), National Institutes of Health Award No. HL-47094 (W.C.S.), and the Medical Research Service of the Department of Veterans Aflairs, San Francisco (J.A. W.). Present address: W.C.S., Institute of Pharmacology (R2-IOI), Syntex Research, 3401 Hillview Ave, Palo Alto, CA 94303. Address reprint requests to William C. Stanley, PhD, Institute of Pharmacology (R2-IOI), Syntex Research, 3401 Hillview Ave. Palo Alto, CA 94303. Copyright 0 1994 by W.B. Saunders Cornpan?, 0026.049519414301~OOiO$O3.OOjO

Fingerprint Dive into the research topics of 'Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine'. Together they form a unique fingerprint.

Cite this