HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Torsten Doenst Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fischer-Rasokat, U. Articles by Doenst, T. Search for Related Content PubMed PubMed Citation Articles by Fischer-Rasokat, U. Articles by Doenst, T. Related Collections Myocardial protection

J Thorac Cardiovasc Surg 2003;126:1806-1812
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Insulin-induced improvement of postischemic recovery is abolished by inhibition of protein kinase C in rat heart

^a Department of Cardiovascular Surgery, Albert-Ludwigs University of Freiburg, Freiburg, Germany

Received for publication January 3, 2003; revisions received June 9, 2003; accepted for publication July 17, 2003.

^* Address for reprints: Torsten Doenst, MD, Department of Cardiovascular Surgery, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg i. Br., Germany
doenst{at}ch11.ukl.uni-freiburg.de

OBJECTIVE: We demonstrated earlier that postischemic addition of insulin improves recovery of function in isolated rat heart by phosphatidylinositol 3-kinase. Activation of phosphatidylinositol 3-kinase before ischemia improves recovery of the heart after ischemia through protein kinase C. We tested whether protein kinase C activation is required for the positive inotropic effect of insulin during reperfusion.

METHODS: Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing [2-³H]glucose (5 mmol/L, 0.05 µCi/mL) plus oleate (0.4 mmol/L) and were subjected to 15 minutes of global ischemia followed by 35 minutes of reperfusion with or without insulin (1 mU/mL). We measured cardiac power, glucose uptake, and tissue metabolites. The protein kinase C inhibitor chelerythrine (5 µmol/L) was added either at the beginning of the experiment or together with insulin. Experiments were repeated under normoxic conditions.

RESULTS: Cardiac power before ischemia was 9.63 to 12.4 mW. Insulin improved recovery of power after ischemia (96.3% ± 10.8% versus 65.7% ± 3.79%, P < .05). This effect was abolished by chelerythrine (55.3% ± 6.49%). However, chelerythrine given at reperfusion did not block insulin's effect on recovery (101.0% ± 4.25%, P < .05). Postischemic glucose uptake was not increased by insulin (3.07 ± 0.32 before, 3.45 ± 0.34 µmol/min/gdw after ischemia, not significant) and was not affected by chelerythrine (3.01 ± 0.26 before, 3.29 ± 0.32 µmol/min/gdw after ischemia, not significant). Under normoxic conditions, chelerythrine did not influence insulin's effects on glucose uptake or power.

CONCLUSION: The results suggest that (1) insulin's effect on recovery is dependent on ischemia-induced protein kinase C activation, (2) the activity of protein kinase C during reperfusion may not be important for this effect of insulin, and (3) protein kinase C plays no role in insulin's effect on glucose uptake under normoxic or postischemic conditions.

This article has been cited by other articles:

				M. Gandhi, B. A. Finegan, and A. S. Clanachan Role of glucose metabolism in the recovery of postischemic LV mechanical function: effects of insulin and other metabolic modulators Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2576 - H2586. [Abstract] [Full Text] [PDF]

				C. Penna, G. Alloatti, S. Cappello, D. Gattullo, G. Berta, B. Mognetti, G. Losano, and P. Pagliaro Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2512 - H2520. [Abstract] [Full Text] [PDF]