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Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion.
Apoptosis. 2004 Nov; 9(6):777-83.A

Abstract

OBJECTIVE

To study the effects of glucose-insulin-potassium (GIK) cocktail on cardiac myocyte apoptosis and cardiac functional recovery following myocardial ischemia/reperfusion (MI/R), and to further determine the role of insulin in the GIK-induced cardioprotective effect in vivo .

METHODS

Forty eight male rabbits were subjected to 40 min MI followed by R for 3 h and were randomly received one of the following treatments: saline, GIK (glucose: 150 g/L, insulin: 60 U/L and KCl: 80 mmol/L), or insulin (n = 16 in each group) at 1 ml x kg(-1) x h(-1), beginning 30 min before MI and continuing throughout the 3 h-reperfusion. Blood glucose, electrolytes, arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the experiment. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (both DNA laddering and TUNEL analysis) were determined in a blinded manner.

RESULTS

MI/R caused significant cardiac dysfunction and myocardial apoptosis (both strong DNA ladder formation and TUNEL-positive staining). Compared with vehicle, GIK-treated rabbits showed protection against MI/R as evidenced by reduced myocardial infarction (19.7% +/- 2.6% vs . 26.8% +/- 3.3% of vehicle, n = 10, P < 0.05), marked decrease in DNA fragmentation and apoptotic index (11.0% +/- 2.1% vs . 20.1% +/- 3.1% of vehicle, n = 6, P < 0.01), significant decrease of plasma CK and LDH and improved recovery of cardiac systolic/diastolic function at the end of R. Treatment with insulin alone decreased blood glucose significantly but still exerted cardioprotective effects comparable with that of GIK.

CONCLUSIONS

GIK exerts cardioprotective effects against postischemic myocardial injury and improves cardiac functional recovery in vivo . Insulin, mainly through the anti-apoptotic effect, plays a key role in the GIK-elicited myocardial protection in MI/R.

Authors+Show Affiliations

Department of Physiology, The Fourth Military Medical University, Xi'an 710032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15505420

Citation

Zhang, H F., et al. "Role of Insulin in the Anti-apoptotic Effect of Glucose-insulin-potassium in Rabbits With Acute Myocardial Ischemia and Reperfusion." Apoptosis : an International Journal On Programmed Cell Death, vol. 9, no. 6, 2004, pp. 777-83.
Zhang HF, Fan Q, Qian XX, et al. Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion. Apoptosis. 2004;9(6):777-83.
Zhang, H. F., Fan, Q., Qian, X. X., Lopez, B. L., Christopher, T. A., Ma, X. L., & Gao, F. (2004). Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion. Apoptosis : an International Journal On Programmed Cell Death, 9(6), 777-83.
Zhang HF, et al. Role of Insulin in the Anti-apoptotic Effect of Glucose-insulin-potassium in Rabbits With Acute Myocardial Ischemia and Reperfusion. Apoptosis. 2004;9(6):777-83. PubMed PMID: 15505420.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion. AU - Zhang,H F, AU - Fan,Q, AU - Qian,X X, AU - Lopez,B L, AU - Christopher,T A, AU - Ma,X L, AU - Gao,F, PY - 2004/10/27/pubmed PY - 2005/4/29/medline PY - 2004/10/27/entrez SP - 777 EP - 83 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 9 IS - 6 N2 - OBJECTIVE: To study the effects of glucose-insulin-potassium (GIK) cocktail on cardiac myocyte apoptosis and cardiac functional recovery following myocardial ischemia/reperfusion (MI/R), and to further determine the role of insulin in the GIK-induced cardioprotective effect in vivo . METHODS: Forty eight male rabbits were subjected to 40 min MI followed by R for 3 h and were randomly received one of the following treatments: saline, GIK (glucose: 150 g/L, insulin: 60 U/L and KCl: 80 mmol/L), or insulin (n = 16 in each group) at 1 ml x kg(-1) x h(-1), beginning 30 min before MI and continuing throughout the 3 h-reperfusion. Blood glucose, electrolytes, arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the experiment. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (both DNA laddering and TUNEL analysis) were determined in a blinded manner. RESULTS: MI/R caused significant cardiac dysfunction and myocardial apoptosis (both strong DNA ladder formation and TUNEL-positive staining). Compared with vehicle, GIK-treated rabbits showed protection against MI/R as evidenced by reduced myocardial infarction (19.7% +/- 2.6% vs . 26.8% +/- 3.3% of vehicle, n = 10, P < 0.05), marked decrease in DNA fragmentation and apoptotic index (11.0% +/- 2.1% vs . 20.1% +/- 3.1% of vehicle, n = 6, P < 0.01), significant decrease of plasma CK and LDH and improved recovery of cardiac systolic/diastolic function at the end of R. Treatment with insulin alone decreased blood glucose significantly but still exerted cardioprotective effects comparable with that of GIK. CONCLUSIONS: GIK exerts cardioprotective effects against postischemic myocardial injury and improves cardiac functional recovery in vivo . Insulin, mainly through the anti-apoptotic effect, plays a key role in the GIK-elicited myocardial protection in MI/R. SN - 1360-8185 UR - https://www.unboundmedicine.com/medline/citation/15505420/Role_of_insulin_in_the_anti_apoptotic_effect_of_glucose_insulin_potassium_in_rabbits_with_acute_myocardial_ischemia_and_reperfusion_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=15505420.ui DB - PRIME DP - Unbound Medicine ER -