Zykov VA, Tuchina TP, Lebedev DA, Krylova IB, Babenko AY, Kuleshova EV, Grineva EN, Bayramov AA, Galagudza MM. Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus. World J Diabetes 2018; 9(9): 149-156 [PMID: 30254724 DOI: 10.4239/wjd.v9.i9.149]
Corresponding Author of This Article
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
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Basic Study
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Zykov VA, Tuchina TP, Lebedev DA, Krylova IB, Babenko AY, Kuleshova EV, Grineva EN, Bayramov AA, Galagudza MM. Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus. World J Diabetes 2018; 9(9): 149-156 [PMID: 30254724 DOI: 10.4239/wjd.v9.i9.149]
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.
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.
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
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.
