THE METABOLIC EFFECT OF CELLULAR PROTEIN KINASES BLOCKADE ON THE EXPERIMENTAL DIABETES
S.V. Ziablitzev1, K.O. Usenko1, O.V. Dobrovinska2, Yu.V. Perepelytsa1, V.A. Andrushchenko1
- Bogomoletz National Medical University, Kyiv, Ukraine
- V.P. Komisarenko Institute of Endocrinology and
Metabolism, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz70.03.016

Abstract
Prospective use of receptor protein kinase inhibitors (PKI)
for the prevention and/or treatment of diabetic complications
necessitates the study of their effect on carbohydrate, lipid,
and protein metabolism in experimental models of type 1
(DM1) and type 2 (DM2) diabetes. DM1 was modeled in
male Wistar rats with streptozotocin administration (50 mg/
kg), DM2 – by long-term (180 days) maintenance on a highcalorie fat diet (HFD; 56,7% fat) with the introduction of a
lower dose of streptozotocin (25 mg/kg). For the treatment,
we used insulin (“Actrapid Novo Nordisk”, Denmark) and
a PKI inhibitor Sorafenib (“Cipla”, India), added orally in
sachet form (150 mg/kg). Regardless of the diet type, the
streptozotocin administration led to hyperglycemia, weight
loss, glucose- and ketonuria, polyuria, and polydipsia. The
severity of these manifestations was heightened in HFD rats,
with a mortality rate of 53.3% observed (when modeling
DM1 – 12%), likely attributed to the onset of liver failure. In
HFD rats, slight hyperglycemia was noted only on the 150th
day. All the diabetes models used were accompanied by significant hypercholesterolemia and hyperlipidemia. The addition of glucose to HFD rats increased the cholesterol content.
HFD caused hypoproteinemia, metabolism suppression and
increased transaminases activity. The established violations
were largely restored with the use of PKI: glycemia level, body
weight loss, the content of triglycerides and very low-density
lipoproteins decreased; an increase in high-density lipoproteins
and the normalization of pigment metabolism were observed.
Keywords:
hyperglycemia; fat diet; streptozotocin; steatohepatosis; hypoproteinemia; hypercholesterolemia; hypertriglyceridemia.
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