The structural analogue of apelin-12 prevents energy disorders in the heart in experimental type 1 diabetes mellitus

    
Studneva I.M.1, Veselova O.M.1, Dobrokhotov I.V.1, Serebryakova L.I.1, Palkeeva M.E.1, Avdeev D.V.1, Molokoedov A.S.1, Sidorova M.V.1, Pisarenko O.I.1

1. Chazov National Medical Research Center of Cardiology, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20247003135      PubMed Id: 38940202
Year: 2024  Volume: 70  Issue: 3  Pages: 135-144
Type 1 diabetes mellitus (T1DM) is the most severe form of diabetes, which is characterized by absolute insulin deficiency induced by the destruction of pancreatic beta cells. The aim of this study was to evaluate the effect of a structural analogue of apelin-12 ((NαMe)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, metilin) on hyperglycemia, mitochondrial (MCh) respiration in permeabilized cardiac left ventricular (LV) fibers, the myocardial energy state, and cardiomyocyte membranes damage in a model of streptozotocin (STZ) diabetes in rats. Metilin was prepared by solid-phase synthesis using the Fmoc strategy and purified using HPLC. Four groups of animals were used: initial state (IS); control (C), diabetic control (D) and diabetic animals additionally treated with metilin (DM). The following parameters have been studied: blood glucose, MCh respiration in LV fibers, the content of cardiac ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr), the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in blood plasma. Administration of metilin to STZ-treated rats decreased blood glucose, increased state 3 oxygen consumption, the respiratory control ratio in MCh of permeabilized LV fibers, and increased the functional coupling of mitochondrial CK (mt-CK) to oxidative phosphorylation compared with these parameters in group D. In STZ-treated animals metilin administration caused an increase in the PCr content and prevention of the loss of total creatine (ΣCr=PCr+Cr) in the diabetic hearts, as well as restoration of the PCr/ATP ratio in the myocardium and a decrease in the activity of CK-MB and LDH in plasma to initial values. Thus, metilin prevented energy disorders disturbances in cardiomyocytes of animals with experimental T1DM.
Download PDF:  
Keywords: apelin-12 analogue, streptozotocin diabetes, rat heart, mitochondrial dysfunction, myocardial energy state
Supplementary materials:
Citation:

Studneva, I. M., Veselova, O. M., Dobrokhotov, I. V., Serebryakova, L. I., Palkeeva, M. E., Avdeev, D. V., Molokoedov, A. S., Sidorova, M. V., Pisarenko, O. I. (2024). The structural analogue of apelin-12 prevents energy disorders in the heart in experimental type 1 diabetes mellitus. Biomeditsinskaya Khimiya, 70(3), 135-144.
References