Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2018; 9(9): 149-156
Published online Sep 15, 2018. doi: 10.4239/wjd.v9.i9.149
Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus
Vladislav A Zykov, Taisiia P Tuchina, Denis A Lebedev, Irina B Krylova, Alina Y Babenko, Elvira V Kuleshova, Elena N Grineva, Alekber A Bayramov, Michael M Galagudza
Vladislav A Zykov, Taisiia P Tuchina, Denis A Lebedev, Alina Y Babenko, Elvira V Kuleshova, Elena N Grineva, Alekber A Bayramov, Michael M Galagudza, Almazov National Medical Research Centre, St-Petersburg 197341, Russia
Irina B Krylova, Institute of Experimental Medicine, St-Petersburg 197376, Russia
Author contributions: Zykov VA, Tuchina TP and Lebedev DA performed the experiments and wrote the manuscript; Babenko AY, Kuleshova EV and Grineva EN performed the literature review and suggested the study concept; Krylova IB and Bayramov AA developed the experimental design and performed data analysis; Galagudza MM provided scientific consulting, coordinated experimental parts, and edited the manuscript.
Supported by Russian Science Foundation, No. 17-75-30052.
Institutional animal care and use committee statement: All animal experiments were performed according to the Guide for the Care and Use of Laboratory Animals in Almazov National Medical Research Centre, which strictly conforms to the Guide for the Care and Use of Laboratory Animals, published by the US National Institutes of Health (NIH, Bethesda, MD). The protocol was approved by the Institutional Animal Care and Use Committee of Almazov National Medical Research Centre (protocol #2016-3).
Conflict-of-interest statement: All authors have no conflicts of interest to report.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alina Y Babenko, DSc, MD, PhD, Doctor, Research Scientist, Institute of Endocrinology, Almazov National Medical Research Centre, Akkuratova St., 2, St-Petersburg 197341, Russia. babenko@almazovcentre.ru
Telephone: +7-921-3314374 Fax: +7-812-7025595
Received: March 27, 2018
Peer-review started: March 27, 2018
First decision: April 23, 2018
Revised: July 3, 2018
Accepted: July 10, 2018
Article in press: July 10, 2018
Published online: September 15, 2018
Processing time: 171 Days and 7.8 Hours
Abstract
AIM

To evaluate the effects of glucagon-like peptide-1 analogs (GLP-1a) combined with insulin on myocardial ischemia-reperfusion injury in diabetic rats.

METHODS

Type 2 diabetes mellitus (T2DM) was induced in male Wistar rats with streptozotocin (65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows: (1) control rats; (2) insulin (0.1 U/kg) treated rats prior to ischemia; (3) insulin (0.1 U/kg) treated rats at reperfusion; (4) GLP-1a (140 mg/kg) treated rats prior to ischemia; (5) GLP-1a (140 mg/kg) treated rats at reperfusion; and (6) rats treated with GLP-1a (140 mg/kg) prior to ischemia plus insulin (0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.

RESULTS

There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size (34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1a had no effect on infarct size. However, pre-ischemic administration of GLP-1a reduced infarct size to 12% ± 2.2% (P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1a prior to ischemia and insulin at reperfusion (8% ± 1.6%, P < 0.05 vs the control and GLP-1a alone treated groups).

CONCLUSION

GLP-1a pre-administration results in myocardial infarct size reduction in rats with T2DM. These effects are maximal in rats treated with GLP-1a pre-ischemia plus insulin at reperfusion.

Keywords: Glucagon-like peptide-1 analog; Insulin; Myocardial ischemia-reperfusion injury; Infarct size; Type 2 diabetes mellitus; Rats; Experimental research

Core tip: In addition to their glucose-lowering effects, glucagon-like peptide-1 analogs (GLP-1a) were shown to exhibit cardioprotective effects. However, the optimal protocol of GLP-1a administration for infarct size reduction has not been determined yet. Additionally, it is important to investigate the effects of GLP-1a combined with other antidiabetic drugs on myocardial infarct size. Thus, we evaluated the effects of GLP-1a with and without insulin on infarct size in rats with type 2 diabetes mellitus. We found that GLP-1a administration prior to ischemia resulted in significant infarct size reduction. Infarct size reduction was maximal in rats treated with GLP-1a before ischemia plus insulin at reperfusion.