Pioglitazone prevents cardiac remodeling in high-fat, high-calorie-induced type 2 diabetes mellitus.

“The agonists of peroxisome proliferator-activated receptor-gamma (PPAR gamma) ameliorate cardiovascular complications associated with diabetes mellitus. We tested the hypothesis that recovery from ailing to failing myocardium in diabetes by PPAR gamma agonist is in part due to decreased matrix metalloproteinase-9 (MMP-9) activation and left ventricular (LV) tissue levels of homocysteine (Hcy),” researchers in the United States report.

W.E. Rodriguez and colleagues at the University of Louisville explained, “C57BL/6J mice were made diabetic (D) by feeding them a high-fat calorie diet. PPAR gamma was activated by adding pioglitazone (Pi) to the diet. After 6 wk, mice were grouped into: normal calorie diet (N), D, N + Pi and D + Pi (n=6 in each group). LV variables were measured by echocardiography, endothelial-myocyte (E-M) coupling was measured in cardiac rings, and MMP-9 activation was measured by zymography.”

The data showed, “Blood glucose levels were twofold higher in D mice compared with N mice. Pi decreased the levels of glucose in D mice to the levels in N mice. LV Hcy levels were 3.5±0.5 mcM in N groups compared with 12.4±0.6 mcM in D groups. Treatment with Pi normalized the LV levels of Hcy but had no effect on plasma levels of Hcy. In the D group, LV contraction was reduced compared with that of the N group and was ameliorated by treatment with Pi. LV wall thickness was reduced to 0.25±0.02 mm in the D group compared with 0.42±0.01 mm in the N group.

“LV diastolic diameter was 3.05±0.01 mm in the D group compared with 2.20±0.02 mm in the N group. LV systolic diameter was 1.19±0.02 mm in the D group and 0.59±0.01 mm in the N group. Pi normalized the LV variables in D mice. The responses to ACh and nitroprusside were attenuated in diabetic hearts, suggesting that there was E-M uncoupling in the D group compared with the N group, which was ameliorated by Pi. Plasma and LV levels of MMP-2 and -9 activities were higher in the D group than in the N group but normalized after Pi treatment.”

The researchers concluded, “These results suggest that E-M uncoupling in the myocardium, in part, is due to increased MMP activities secondary to suppressing PPAR gamma activity in high-fat, calorie-induced Type 2 diabetes mellitus.”

Rodriguez and colleagues published their study in American Journal of Physiology - Heart and Circulatory Physiology (Pioglitazone prevents cardiac remodeling in high-fat, high-calorie-induced Type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol, 2006;291(1):H81-H87).

For additional information, contact S.C. Tyagi, University of Louisville, School Medical, Dept. of Physics & Biophysics, A-1115, 500 S Preston St., Louisville, KY 40202, USA.

Publisher contact information for the American Journal of Physiology - Heart and Circulatory Physiology is: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA.