Study of Na+/K+-ATPase and Components of the Ca2+-Transporting System in Myocardium under Experimental Prediabetes and Type 1 Diabetes in Rats

• Published in: Journal of evolutionary biochemistry and physiology Vol. 60; no. 3; pp. 1163 - 1174
• Main Authors: Sukhov, I. B., Chistyakova, O. V., Dobretsov, M. G.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-05-2024; Springer Nature B.V
• Subjects: Animal models; Animal Physiology; Biochemistry; Biomedical and Life Sciences; Ca2+-transporting ATPase; Calcium phosphates; Calcium transport; Cardiomyocytes; Cardiomyopathy; Diabetes; Diabetes mellitus (insulin dependent); Evolutionary Biology; Experimental Papers; Gene expression; Genes; Hyperglycemia; Isoforms; Life Sciences; Magnesium; Molecular modelling; Myocardium; Na+/K+-exchanging ATPase; Ouabain; Potassium; Potassium channels (inwardly-rectifying); Potassium channels (voltage-gated); Streptozocin; SERCA2; Na; insulin; rat; prediabetes; ATPase; diabetes mellitus; diabetic cardiomyopathy; K
• ISSN: 0022-0930; 1608-3202
• DOI: 10.1134/S0022093024030232

One of the complications of diabetes mellitus (DM) is diabetic cardiomyopathy (DCM), whose molecular mechanisms of pathogenesis have not been fully studied. Previously, the involvement of Na
+
/K
+
-ATPase and components of the Ca
2+
transport system in cardiomyocytes in the development of DCM was shown. The aim of the work was to study the expression and activity of Na
+
/K
+
-ATPase and Ca
2+
-ATPase (SERCA2) in the myocardium of male Wistar rats in a model of streptozotocin (STZ)-induced prediabetes and overt type 1 diabetes (T1DM). STZ was administered at once i.p. in doses of 30–35 mg/kg. Rats with glucose levels above 11 mM were considered diabetic (STZ-D1 group), and those with moderate hyperglycemia were considered prediabetic (STZ-preD1 group). The activity of Na
+
/K
+
-ATPase and Ca
2+
-ATPase was determined (by the rate of release of inorganic phosphate, P
i
), and the expression of the genes α1- and α2-isoforms of Na
+
/K
+
-ATPase, SERCA2, and Kir6.1, Kv7.1, and Kv2.1 potassium channels was also determined. In the control (C) group, the activity of ouabain (1 mM) -sensitive Mg
2+
-dependent ATPase was 6.03 ± 0.6 mmol Pi/g/h. In the STZ-D1 and STZ-preD1 groups, Na
+
/K
+
-ATPase activity did not differ from group C. The level of gene expression of α1- and α2- subunits of Na
+
/K
+
-ATPase in the STZ-D1 group decreased by more than 45%, then both in the STZ-preD1 group increased by 64 and 81%, which may indicate a high sensitivity of expression to insulinopenia. The activity of Ca
2+
-ATPase and the expression of the SERCA2 gene did not differ between the groups, which might be because the 4-week period after STZ administration is not sufficient for the development of Ca
2+
-ATPase deficiency in the rat heart. The level of expression of the genes of the potassium channel subtypes Kv2.1, Kir6.1, and Kv7.1 increased in the STZ-preD1 group, which may indicate a potential contribution of the studied potassium channel subtypes to the adaptation mechanism to moderate hyperglycemia.