Cardioprotection by Glucose-Insulin-Potassium: Dependence on K_ATP Channel Opening and Blood Glucose Concentration Before Ischemia

Authors

John F. LaDisa, Marquette UniversityFollow
John G. Krolikowski, Medical College of WisconsinFollow
Paul S. Pagel, Marquette UniversityFollow
David C. Warltier, Marquette UniversityFollow
Judy R. Kersten, Medical College of Wisconsin

Document Type

Article

Language

eng

Format of Original

7 p.

Publication Date

8-1-2004

Publisher

American Physiological Society

Source Publication

American Journal of Physiology - Heart and Circulatory Physiology

Source ISSN

0363-6135

Original Item ID

doi: 10.1152/ajpheart.00122.2004

Abstract

We tested the hypothesis that glucose-insulin-potassium (GIK)-induced protection against myocardial infarction depends on ATP-dependent K⁺ (K_ATP) channel activation and is abolished by hyperglycemia before the ischemia. Dogs were subjected to a 60-min coronary artery occlusion and 3-h reperfusion in the absence or presence of GIK (25% dextrose; 50 IU insulin/l; 80 mM/l KCl infused at 1.5 ml·kg⁻¹·h⁻¹) beginning 75 min before coronary artery occlusion or 5 min before reperfusion. The role of K_ATP channels was evaluated by pretreatment with glyburide (0.1 mg/kg). The efficacy of GIK was investigated with increases in blood glucose (BG) concentrations to 300 or 600 mg/dl or experimental diabetes (alloxan/streptozotocin). Infarct size (IS) was 29 ± 2% of the area at risk in control experiments. GIK decreased (P < 0.05) IS when administered beginning 5 min before reperfusion. This protective action was independent of BG (13 ± 2 and 12 ± 2% of area at risk; BG = 80 or 600 mg/dl, respectively) but was abolished in dogs receiving glyburide (30 ± 4%), hyperglycemia before ischemia (27 ± 4%), or diabetes (25 ± 3%). IS was unchanged by GIK when administered before ischemia independent of BG (31 ± 3, 27 ± 2, and 35 ± 3%; BG = 80, 300, and 600 mg/dl, respectively). The insulin component of GIK promotes cardioprotection by K_ATP channel activation. However, glucose decreases K_ATP channel activity, and this effect predominates when hyperglycemia is present before ischemia.

Comments

Accepted version. American Journal of Physiology - Heart and Circulatory Physiology, Vol. 287 (August 1, 2004): H601-H607. DOI. © 2004 American Physiological Society. Used with permission.

Recommended Citation

LaDisa, John F.; Krolikowski, John G.; Pagel, Paul S.; Warltier, David C.; and Kersten, Judy R., "Cardioprotection by Glucose-Insulin-Potassium: Dependence on K_ATP Channel Opening and Blood Glucose Concentration Before Ischemia" (2004). Biomedical Engineering Faculty Research and Publications. 216.
https://epublications.marquette.edu/bioengin_fac/216