Effect of chronic sulfonylurea treatment on the myocardium of insulin-dependent diabetic rats.
Adult rats treated with high doses of streptozocin became progressively more hyperglycemic during the first month of the diabetic condition. Treatment of these rats with the sulfonylurea glyburide halted, and in some cases, reversed this process in a high percentage of the diabetics. Associated with the glyburide-mediated improvement in fasting blood glucose levels was an increase in myocardial glucose utilization and lactate production. The stimulation of myocardial glucose utilization by insulin was greater in glyburide-treated hearts, indicating that the hyperglycemic agent increased insulin responsiveness. The sulfonylurea also partially restored insulin sensitivity to the normal range. In agreement with previous studies, myocardial mechanical function was significantly impaired in the diabetic heart. When treated with glyburide, the severity of the mechanical defect was significantly less. The sulfonylurea also promoted an increase in myosin ATPase activity and a shift in the myosin isozyme pattern in favour of the most active V1 form. These results imply that glyburide therapy can provide benefit to the diabetic heart by improving energy metabolism and promoting a shift in myosin towards the most active form.
Mozaffari
M S
MS
Department of Pharmacology, University of South Alabama College of Medicine, Mobile 36688.
Wilson
G L
GL
Schaffer
S W
SW
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000627:therapeutic use*; D007527:Isoenzymes / Q000302:isolation & purification; D007773:Lactates / Q000378:metabolism; D008297:Male; D009218:Myosins / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
D007328:Insulin; D007527:Isoenzymes; D007773:Lactates; D013453:Sulfonylurea Compounds; D009218:Myosins; D005947:Glucose; D005905:Glyburide