title: Prevention of diabetes-induced myocardial dysfunction in rats by methyl palmoxirate and triiodothyronine treatment.
abstract: Diabetes results in myocardial functional alterations which are accompanied by a depression of biochemical parameters such as myosin ATPase and calcium uptake in the sarcoplasmic reticulum. Methyl palmoxirate, a fatty acid analog, is reported to decrease circulating glucose levels by inhibiting fatty acid metabolism, thus forcing carbohydrate utilization. In the present study, we attempted to prevent streptozotocin diabetes-induced myocardial alterations in the rat. Using the isolated working heart preparation, we observed a depression of myocardial function in rats 6 weeks after the induction of diabetes, which was characterized by the inability of these hearts to develop left ventricular pressures and rates of ventricular contraction and relaxation as well as control hearts at higher left atrial filling pressures. Methyl palmoxirate treatment (25 mg kg-1 day-1 po daily) was unable to control diabetes-induced changes in plasma glucose, triglycerides, insulin, and total lipids. Also, the functional depression seen in diabetic rat hearts was present despite the treatment. However, depression of calcium uptake and elevation of long chain acyl carnitines seen in sarcoplasmic reticulum (SR) prepared from diabetic rat hearts could be prevented by the treatment. As triiodothyronine (T3) treatment has been shown to normalize depression of cardiac myosin ATPase in diabetic rats, we repeated the study using a combination of T3 (30 micrograms kg-1 day-1 sc daily) and methyl palmoxirate. While diabetic rats treated with T3 alone did not show significant improvement of myocardial function when compared with untreated diabetics, the function of those treated with both T3 and methyl palmoxirate was not significantly different from that in control rat hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.forename: A G
authors.initials: AG
authors.lastname: Tahiliani
authors.forename: J H
authors.initials: JH
authors.lastname: McNeill
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology / Q000517:prevention & control*; D004852:Epoxy Compounds / Q000627:therapeutic use*; D004988:Ethers, Cyclic / Q000627:therapeutic use*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D011422:Propionates / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood; D014284:Triiodothyronine / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D011422:Propionates; D013963:Thyroid Hormones; D014284:Triiodothyronine; D000251:Adenosine Triphosphatases; C017522:methyl 2-tetradecylglycidate; D002118:Calcium