2337-PUB: Impact of Treatment with Insulin and Other Hypoglycemic Drugs on 5'-AMP-Activated Protein Kinase Activity in Leukocytes of Patients with Type 2 Diabetes

Abstract

Background: The leukocytes play an essential role in the development of pathological conditions such as diabetes and its complications. The 5'-adenosine monophosphate-activated protein kinase (AMPK), which usually is inhibited in T2D, controls the energy balance of the cell. Aim: To study the phosphorylation of AMPK α-subunit (Thr172), and thus its activation, in blood cells at combined T2D patients treatment with insulin, metformin and dapagliflozin. Methods: To determine the amount of phospho-AMPK (phospho-threonine 172) enzyme-linked immunosorbent assay (ELISA) kit ab154468 (Abcam, UK) was used. The results of the study are presented as M ± SD, n = 3-6. To compare the data groups, Student's t-test was used. Values of P ≤ 0.05 were considered as significant. Results: It has been shown that metformin increased the activity of AMPK in the leukocytes of patients with T2D more than 3-6 times compared with patients before treatment. Dapagliflozin increases the activity of AMPK and enhances the effect of metformin in the leucocytes of patients with T2D. The mechanisms of drug interaction and the consequences of their antagonism are discussed. Conclusion: AMPK activity in leukocytes may be additional indicator of the effectiveness of the hypoglycemic drugs action and status of the disease. Disclosure V.V. Pushkarev: None. L.K. Sokolova: None. V.M. Pushkarev: None. T. Vatseba: None. M.D. Tronko: None.

Рівень Ендотеліну‑1 У Крові Хворих На Діабет На Тлі Терапії Цукрознижуваль Ними Препаратами

“…Metformin-mediated activation of AMPK inhibits the NF-кВ cascade, resulting in improved insulin signaling [1,12]. However, insulin suppresses AMPK activity in leucocytes, liver, muscles, and possibly in other tissues and organs [15,16]. There is a certain independence of the insulin signal pathway (PI3K/Akt) from the cascade of AMPK activation (LKB1, CAM-KK2, and TAK1 (TGFβ-activated kinase 1).…”