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Effects of chronic treatment with glibenclamide and/or metformin on the resistance to ischaemia of isolated hearts from Zucker Diabetic Fatty rats (ZDF/GMI-fa/fa)

Laboratoire de Bioénergétique Fondamentale et Appliquée (EMI 02-21) BP 53X, F-38041 Grenoble Cedex 9, France, Nicole.Lavanchy{at}ujf-grenoble.fr

Georges Christe

Groupe d'Electrophysiologie Moléculaire, Laboratoire de Développement et Vieillissement de l'Endothélium (EMI 02-19), BP 53X, F-38041 Grenoble Cedex 9, France

Francine Cand

Groupe d'Electrophysiologie Moléculaire, Laboratoire de Développement et Vieillissement de l'Endothélium (EMI 02-19), BP 53X, F-38041 Grenoble Cedex 9, France

Nicolas Wiernsperger

Merck-Lipha S.A., 37 Rue Saint Romain, F-69379 Lyon Cedex 08, France

Jean Verdetti

Groupe d'Electrophysiologie Moléculaire, Laboratoire de Développement et Vieillissement de l'Endothélium (EMI 02-19), BP 53X, F-38041 Grenoble Cedex 9, France

The study was carried out to determine whether metformin (M) had any deleterious effect on the tolerance to ischaemia of the isolated diabetic rat when administered chronically in combination with glibenclamide (G). The male Zucker Diabetic Fatty (ZDF) rat served as a model of type 2 diabetes that resembles the human syndrome. Three groups of rats were treated for one month with M (100 mg/kg) or G (2 mg/kg) or G + M in their daily food. One group was untreated (C). Aortically perfused hearts were subjected to a 25-minute global low-flow ischaemia and a 30-minute reperfusion. Heart rate (HR), left ventricular developed pressure (LVDP), rate pressure product (RPP) and coronary flow (CF) were monitored.

When compared to C hearts, the hearts from G + M rats showed improvements in HR, LVDP and RPP at the end of reperfusion. Hearts from G and M rats exhibited no difference. Myocardial glycogen stores at the end of in the three other groups.

The study did not reveal any deleterious effect of the chronic G + M therapy on the functional recovery of the isolated diabetic heart submitted to ischaemia and reperfusion: indeed, an increase in residual contractile capacity was found.

Key Words: diabetes type 2 • ZDF rats • isolated heart • glibenclamide • metformin • chronic treatment.

References

• UK Prospective Diabetes Study Group (UKPDS). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-65.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Wiernsperger NF Metformin: intrinsic vasculoprotective properties. Diab Technol Ther 2000;2:259-72.[CrossRef]
• Sgambato S., Varricchio M., Tesauro P. et al. The use of metformin in ischemic cardiopathy. Clin Ter 1980;94:77-85.[Medline] [Order article via Infotrieve]
• Olsson J., Lindberg G., Gottsater M. et al. Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study. Diabetologia 2000;43:558-60.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Bruno G., Merletti F., Boffetta P. et al. Impact of glycæmic control, hypertension and insulin treatment on general and cause-specific mortality: an Italian population-based cohort of type II (non-insulin-dependent) diabetes mellitus. Diabetologia 1999;42:297-301.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Fisman EZ, Tenenbaum A., Benderly M. et al. Antihyperglycemic treatment in diabetics with coronary disease: increased metformin-associated mortality over a 5-year follow-up. Cardiology 1999;91:195-202.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Fisman EZ, Tenenbaum A., Boyko V. et al. Oral antidiabetic treatment in patients with coronary disease: time-related increased mortality on combined glyburide/metformin therapy over a 7.7-year follow-up. Clin Cardiol 2001;24:151-8.[Web of Science][Medline] [Order article via Infotrieve]
• Johnson J., Sumit R., Simpson S. et al. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care 2002;25:2244-8.[Abstract/Free Full Text]
• Mozaffari MS, Wilson GL and Schaffer SW Effect of chronic sulfonylurea treatment on the myocardium of insulin-dependent diabetic rats. Can J Physiol Pharmacol 1988;66:1481-6.[Web of Science][Medline] [Order article via Infotrieve]
• Ozuari A., Ozturk Y., Yildizoglu-Ari N. et al. The effects of glyburide and insulin on the cardiac performance in rats with non-insulin-dependent diabetus mellitus. Gen Pharmacol 1993;24:165-9.[Web of Science][Medline] [Order article via Infotrieve]
• Garnier A., Rossi A., Lavanchy N. Importance of the early alterations of energy metabolism in the induction and the disappearance of ischemic preconditioning in the isolated rat heart. J Mol Cell Cardiol 1996;28:
• Bergmeyer HU Methods in Enzymatic Analysis. Academic Press, Inc. 1974;vol 3:1127-31.
• Friedman JE, de Vente JE, Peterson RG et al. Altered expession of muscle glucose transporter GLUT-4 in diabetic fatty Zucker rats (ZDF/Drt-fa). Am J Physiol 1991;261:E782-E788.[Web of Science][Medline] [Order article via Infotrieve]
• Scognamiglio R., H Avogaro A., Vigili de Kreutzenberg S. et al. Effects of treatment with sulfonylurea drugs or insulin on ischemia-induced myocardial dysfunction in type 2 diabetes. Diabetes 2002;51:808-12.[Abstract/Free Full Text]
• Klepzig H., Kober G., Matter C. et al. Sulfonylureas and ischaemic preconditioning: a double-blind, placebo-controlled evaluation of glimepiride and glibenclamide. Eur Heart J 1999;20:439-46.[Abstract/Free Full Text]
• Oshiro K., Murakami K., Sunagawa R. et al. Chronic effects of tolbutamide on myocardial tension during ischemia and reperfusion in perfused hearts isolated from insulin dependent and non insulin dependent diabetic rats. Jpn Heart J 1991;32:347-64.[Medline] [Order article via Infotrieve]
• Shimabukuro M., Nagamine F., Murakami K. et al. Chronic glicazide treatment affects basal and post-ischemic cardiac function in diabetic rats. Gen Pharmacol 1994;25:697-704.[Web of Science][Medline] [Order article via Infotrieve]
• Tosaki A., Engelman DT, Engelman RM et al. Diabetes and ATP-sensitive potassium channel openers and blockers in isolated ischemic-reperfused hearts. J Pharmacol Exp Ther 1995;275:1115-23.[Abstract/Free Full Text]
• Verma S., McNeill JH Metformin improves cardiac function in isolated streptozotocin-diabetic rat hearts. Am J Physiol 1994;266:H714-H719.[Web of Science][Medline] [Order article via Infotrieve]
• Legtenberg RJ, Houston RJ, Oeseburg B. et al. Metformin improves cardiac functional recovery after ischemia in rats. Horm Metab Res 2002;34: 182-5.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Legtenberg RJ, Houston RJ, Smits P., Oeseburg B. Hemodynamic changes by glibenclamide in isolated, working erythrocyte perfused rat heart. Adv Exp Med Biol 1999;471:257-63.[Web of Science][Medline] [Order article via Infotrieve]

The British Journal of Diabetes & Vascular Disease, Vol. 3, No. 5, 375-380 (2003)
DOI: 10.1177/14746514030030051301


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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Lavanchy, N. Articles by Verdetti, J. Search for Related Content Social Bookmarking                         What's this?