Decreased myocardial glucose uptake during ischemia in diabetic swine.
The purpose of the study was to assess myocardial glucose uptake in nondiabetic (n = 5) and streptozotocin-diabetic (n = 6) Yucatan miniature swine under matched hyperglycemic and hypoinsulinemic conditions. Fasting conscious diabetic swine had significantly higher plasma glucose levels (20.9 +/- 2.6 v 5.2 +/- 0.3 mmol/L) and lower insulin levels (6 +/- 1 v 14 +/- 4 microU/mL) than nondiabetic animals. Myocardial glucose uptake was measured in open-chest anesthetized animals under aerobic and ischemic conditions 12 weeks after streptozotocin treatment. Coronary blood flow was controlled by an extracorporeal perfusion circuit. Ischemia was induced by reducing left anterior descending (LAD) coronary artery blood flow by 60% for 40 minutes. Animals were treated with somatostatin to suppress insulin secretion, and nondiabetic swine received intravenous (IV) glucose to match the hyperglycemia in the diabetic animals. The rate of glucose uptake by the myocardium was not statistically different under aerobic conditions, but was significantly lower in diabetic swine during ischemia (0.20 +/- 0.08 v 0.63 +/- 0.14 micromol x g(-1) x min(-1), P < .01). Myocardial glucose transporter (GLUT4) protein concentration was decreased by 31% in diabetic swine. In conclusion, 12 weeks of streptozotocin diabetes in swine caused a significant decrease in myocardial GLUT4 protein and a decrease in myocardial glucose uptake during ischemia.
Stanley
W C
WC
Section of Cardiovascular Pharmacology, Syntex Discovery Research, Palo Alto, CA, USA.
Hall
J L
JL
Hacker
T A
TA
Hernandez
L A
LA
Whitesell
L F
LF
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003326:Coronary Circulation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000032:analysis; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature; D016276:Ventricular Function / Q000502:physiology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D019344:Lactic Acid; D005947:Glucose