Blockade of L-type calcium channels alters hepatic mitochondrial function in insulin-resistant rats
Authors:   Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine, Zavhorodnii M.O. ,   International Centre of Astronomical, Medical and Ecological Researches (ICAMER) NAS of Ukraine, Ukraine, Nosar V.I. ,   Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine, Gonchar O.O. ,   Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine, Tsapenko P.K. ,   Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine,   International Centre of Astronomical, Medical and Ecological Researches (ICAMER) NAS of Ukraine, Ukraine, Kozlovska M.G. ,   Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine, Vasylenko M.I. ,   Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine,   International Centre of Astronomical, Medical and Ecological Researches (ICAMER) NAS of Ukraine, Ukraine, Portnichenko V.I. ,   Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine,   International Centre of Astronomical, Medical and Ecological Researches (ICAMER) NAS of Ukraine, Ukraine, Portnychenko A.G. ,   Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine,   International Centre of Astronomical, Medical and Ecological Researches (ICAMER) NAS of Ukraine, Ukraine
Published: December 2023

Mitochondria are central organelles in maintaining energy and oxidative homeostasis. Despite intensive research, the function of mitochondria and the mechanisms of its regulation under physiological conditions and in insulin resistance require detailed investigation. The aim of this study was to investigate the effect of blockade L-type calcium channels in insulin-resistant rats on hepatic mitochondrial oxidative function and changes in its oxidative status. Insulin resistance was modeled in 6-month-old male Wistar rats by 14 days of high-fat feeding. Standard fed animals served as controls. Verapamil was administered intraperitoneally at a dose of 1 mg/kg to block L-type calcium channels. Indicators of pro- and antioxidant systems (active products of tiobarbituric acid, reduced glutathione, catalase, Cu,Zn-superoxide dismutase) were assayed in the liver homogenate extracted from anesthetized animals after 3 h. Mitochondrial function was studied by the Chance polarographic method using different metabolic substrates. It was shown that in intact animals blockade of L-type calcium channels reduced the efficiency of mitochondrial respiration (V3/V4) in liver mitochondria during oxidation of all substrates through an inhibitory effect on the phosphorylation respiration (V3) and a stimulatory effect on the controlled respiration (V4), without affecting the oxidative status of the liver. In rats with insulin resistance the rate of V3 during oxidation of both NAD- and FADdependent substrates was decreased, violations of oxidative status and increased antioxidant protection were detected. However, in insulin-resistant rats blockade of L-type calcium channels significantly enhanced basic respiration (V2) during NAD-dependent substrate oxidation, V3 and V4 during palmitoyl lipid substrate oxidation, reduced the V3/V4 ratio compared to control, and partially or fully restored the violation of the oxidative status. This may indicate the involvement of calcium mechanisms in the disturbance of the oxidative status of the liver and the regulation of energy metabolism in mitochondria during insulin resistance.