Laser Doppler flowmetry in assessing the effect of liraglutide on microcirculation in rats with absolute insulin deficiency

Abstract

Laser Doppler flowmetry in assessing the effect of liraglutide on microcirculation in rats with absolute insulin deficiency

Era B. Popyhova, Tatiana V. Stepanova, Angelina A. Savkina, Daria D. Lagutina, Aleksei N. Ivanov
Saratov State Medical University n.a. V.I. Razumovsky, Central Scientific Research Laboratory, 137 Bolshaya Sadovaya St., Saratov, 410009, Russia
Introduction: The medical and social significance of diabetes is determined by the high prevalence of the disease, as well as the development of macro- and microvascular complications in patients. The research of the angiotropic effect of liraglutide is of scientific and practical interest. The positive effect of using liraglutide in type 2 diabetes mellitus (DM) has been demostrated. There are some data on the positive effect of using liraglutide in the treatment of type 1 diabetes, but it has not yet been fully studied in clinical practice. In this regard, the purpose of this study was to research, using laser Doppler fluometry (LDF), the effect of liraglutide on microcirculation (MC) in white outbred rats under conditions of absolute insulin deficiency with the alloxan diabetes.
Materials and methods: The studies were performed on 70 white outbred rats, divided into groups: 1) control group (intact animals); 2) comparison group (DM) - animals with the alloxan diabetes; 3) experimental group no.1 (liraglutide low dose (LLD)) – animals with the alloxan diabetes, which were injected by liraglutide at dosase of 0.2 mg/kg/day; 4) experimental group no. 2 (liraglutide high dose (LHD)) - animals with the alloxan diabetes, which were injected by liraglutide at dosage of 0.4 mg/kg/day. The carbohydrate metabolism disorders, the MC of posterior paw skin, as well as the concentration of catecholamines (CA) and markers of endothelial alteration in blood were estimated at the 42nd day of the experiment in the comparison and experimental groups.
Results. It was found that the use of liraglutide normalizes carbohydrate metabolism and cutaneous perfusion of the back of the paws of the rats. Restoration of MC is associated with a decrease in vascular tone and stimulation of endothelium-dependent vasodilation caused by a decrease in serum concentrations of CA, endothelin-1, and asymmetric dimethylarginine (ADMA). Also, the injection of liraglutide at the alloxan diabetes leads to a decrease in the vascular endothelial growth factor (VEGF).
Conclusion: The injection of liraglutide normalizes carbohydrate metabolism and corrects MC in rats with diabetes. The demonstrated recovery of MC by liraglutide provides new prospects for its approval as a drug for pathogenetic correction of MC disorders in the type 1 DM. Correspondence of the results of biochemical, cytochemical and functional studies in DM and against the background of its correction with liraglutide indicates the advisability of using LDF for diagnosing MC disorders caused by impaired carbohydrate metabolism.

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Popyhova Era B.
Saratov State Medical University n.a. V.I. Razumovsky
Russia

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