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
ARTICLE HIGHLIGHTS
Research background

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of myocardial infarction (MI) and poorer prognosis. Recent studies demonstrate that glucagon-like peptide-1 analogs (GLP-1a) possess infarct-limiting effects in experimental settings. However, it is not clear whether GLP-1a have beneficial effects when combined with insulin.

Research motivation

In this study, we intended to compare the cardioprotective effects of GLP-1a therapy with and without concomitant insulin in acute MI in rats with T2DM.

Research objectives

The effects of pre- and post-ischemic GLP-1a and insulin administration on infarct size were studied in the rat model of MI. The effect of a combination of GLP-1a and insulin was assessed in a separate group.

Research methods

We induced T2DM in Wistar rats with streptozotocin at a dose of 65 mg/kg. Myocardial ischemia was induced by left coronary artery occlusion. Myocardial infarct size was determined histochemically. In addition, we analyzed the number and severity of hypoglycemia episodes in the experimental groups. Animals were treated with either GLP-1a or insulin.

Research results

Results of our study show that using GLP-1a before ischemia-reperfusion significantly reduced infarct size. The maximal infarct size reduction was observed in the group treated with GLP-1a prior to ischemia and insulin at reperfusion.

Research conclusions

We have shown that insulin infusion before ischemia increased infarct size, while GLP-1a demonstrated cardioprotective effects. Post-ischemic administration of insulin or GLP-1a had no effect on infarct size. Thus, the regimen of GLP-1a and insulin administration is crucial for expression of their cardioprotective effect.

Research perspectives

Further studies with larger sample sizes can be conducted in order to develop a clinical trial and introduce new combinations of drugs with antidiabetic activity for MI therapy in patients with T2DM.