Tag Archives: insulin resistance

Insulin resistance in obese adolescents and adult men modifies the expression of proliferation related genes

O. H. Minchenko1, Y. M. Viletska1, D. O. Minchenko1,2, V. V. Davydov3

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ominchenko@yahoo.com;
2Bohomolets National Medical University, Kyiv, Ukraine
3SI “Institute of Children and Adolescent Health Care,
National Academy of Medical Sciences of Ukraine”, Kharkiv

Received: 11 December 2018; Accepted: 14 March 2019

Numerous data demonstrate that key regulatory factors, enzymes and receptors including HSPA5, MEST, SLC1A3, PDGFC, and ADM represent poly-functional, endoplasmic reticulum stress-dependent proteins, which control variable metabolic pathways. The expression level of genes of these proteins in the blood and subcutaneous adipose tissue of obese adolescents and adult men with and without insulin resistance was studied. It was shown that in blood of obese adolescents without insulin resistance the expression level of SLC1A3, HSPA5, MEST, and PDGFC genes was significantly increased, but development of insulin resis­tance led to down-regulation of these genes expression except HSPA5 gene as compared to the control group as well as to the group of obese adolescents without insulin resistance. At the same time, the expression level of ADM gene did not change significantly in obese adolescents without insulin resistance, but the development of insulin resistance led to down-regulation of this gene expression. In subcutaneous adipose tissue of obese adult men without insulin resistance the level of SLC1A3 gene expression was decreased, although ADM, MEST, and HSPA5 genes – increased. It was also shown that the development of insulin resistance in obese men affected the expression level of ADM and SLC1A3 genes only. Results of this investigation provide evidence that insulin resistance in obese adolescents and adult men is associated with specific changes in the expression of genes, which related to proliferation and development of obesity and insulin resistance as well as to endoplasmic reticulum stress and contribute to the development of obesity complications.

Blood coagulation and aortic wall integrity in rats with obesity-induced insulin resistance

O. S. Dziuba1, V. O. Chernyshenko1, Ie. A. Hudz1, L. O. Kasatkina1, T. M. Chernyshenko1,
P. P. Klymenko2, H. V. Kosiakova1, T. M. Platonova1, N. M. Hula1, E. V. Lugovskoy1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: oksana.dziuba86@gmail.com;
2State Institute of Gerontology of AMS of Ukraine, Kyiv

Obesity is an important factor in pathogenesis of disorders caused by chronic inflammation. Diet-induced obesity leads to dyslipidemia and insulin resistance (IR) that in turn provoke the development of type 2 diabetes and cardiovascular diseases. Thus, the aim of this work was to investigate the possible pro-atherogenic effects in the blood coagulation system and aortic wall of rats with obesity-induced IR. The experimental model was induced by a 6-month high-fat diet (HFD) in white rats. Blood samples were collected from 7 control and 14 obese IR rats. Prothrombin time (PT) and partial activated thromboplastin time (APTT) were performed by standard methods using Coagulometer Solar СТ 2410. Fibrinogen concentration in the blood plasma was determined by the modified spectrophotometric method. Levels of protein C (PC), prothrombin and factor X were measured using specific chromogenic substrates and activa­ting enzymes from snake venoms. Platelet aggregation was measured and their count determined using Aggregometer Solar AP2110. The aorta samples were stained by hematoxylin and eosin according to Ehrlich. Aortic wall thickness was measured using morphometric program Image J. Statistical analysis was performed using Mann-Whitney U Test. The haemostasis system was characterized by estimation of the levels of individual coagulation factors, anticoagulant system involvement and platelet reactivity. PT and APTT demonstrated that blood coagulation time strongly tended to decrease in obese IR rats in comparison to the control group. It was also detec­ted that 30% of studied obese IR rats had decreased factor X level, 40% had decreased level of prothrombin whereas fibrinogen concentration was slightly increased up to 3 mg/ml in 37% of obese IR rats. A prominent decrease of anticoagulant PC in blood plasma of obese rats was detected. Obese IR rats also had increased platelet count and higher rate of platelet aggregation in comparison to control animals. Histological analysis identified the disruption of aorta endothelium and tendency for the thickening of the aorta wall in the group with obesity-induced IR compared to the group of control rats. Changes of individual coagulation factors were assumed as the evidence of imbalance in the blood coagulation system. Increase of fibrinogen level, drop in PC concentration and pathological platelet reactivity were taken to corroborate the development of low-grade inflammation in obese IR rats. Instant generation of small amounts of thrombin in their blood plasma is expected. Since the aorta morphology assay detected the trend of its wall to thicken and the emergence of disruptions, we assumed there were initial stages of atherosclerosis and the danger of developing atherothrombosis. We detected an increase of blood coagulability and changes in aorta morphology in rats with obesity-induced IR which we assume indicate early development of atherosclerosis.

The impact of hydroxycitric acid on the lipid metabolism profile under experimental insulin resistance syndrome of Syrian hamsters

A. L. Zagayko, A. I. Shkapo, V. P. Fylymonenko, T. O. Briukhanova

National University of Pharmacy, Kharkiv, Ukraine;
e-mail: vpfylymonenko@gmail.com

The syndrome of insulin resistance (IR) is one of the leading reasons for the increased risk of cardiovascular diseases and their complications. Among the key components of IR are obesity and dyslipidemia. Hydroxycitric acid (HCA), an inhibitor of a key enzyme of lipogenesis ATP citrate lyase (ACLY) is a promising obesity treatment agent. The aim of this work was to investigate the effect of HCA on lipid and lipoproteins content in the blood serum, as well as lipid content and activity of some lipid metabolism enzymes in the liver of hamsters with IR. IR was modeled by keeping animals on high-fat diet with addition of fructose. Lipid content was determined by using standard reagent kits, the level of lipoproteins, the activity of glucose 6-phosphate dehydrogenase and ACLY – spectrophotometrically, lysosomal lipase activity – fluorimetrically. Development of hyperlipidemia and atherogenic dyslipidemia, lipid accumulation in the liver, activation of lysosomal lipase and ACLY and reduction of glucose 6-phosphate dehydrogenase activity were shown under IR. The treatment by HCA reduces the manifestations of hyperlipidemia, but enhances the lipid accumulation in the liver.

Biological role of fetuin A and its potential importance for prediction of cardiovascular risk in patients with type 2 diabetes mellitus

M. Yu. Gorshunska1, Y. I. Karachentsev1,2, N. A. Kravchun2, E. Jansen3,
Zh. A. Leshchenko2, A. I. Gladkih2, N. S. Krasova2,
T. V. Tyzhnenko2, Y. A. Opaleyko2, V. V. Роltorak2

1Kharkiv Postgraduate Medical Academy,Ukraine;
2SI V. Danilevsky Institute of Endocrine Pathology Problems,
National Academy of Medical Sciences of Ukraine, Kharkiv;
3National Institute for Public Health and the Environment,
Bilthoven, Netherlands;
e-mail: maryanagr@mail.ru

The authors’ data and those from literature concerning biological role of fetuin A glycoprotein have been generalized in the article. A direct correlation has been established between fetuin A and some adipokines involved in the formation of insulin resistance and atherogenesis (progranu­lin, omentin-1), and osteoprotegerin (the novel cardiovascular risk factor) as well as an increase of circulating levels of fetuin A in patients with type 2 diabetes mellitus with high cardiovascular risk metabolic pattern but without manifestations of macrovascular complications. This substantiates the involvement of fetuin A in the complex of biomarkers of subclinical atherosclerosis.

The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity

O. V. Onopchenko, G. V. Kosiakova, T. M. Goridko, V. M. Klimashevsky, N. M. Hula

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: onop.89.av@mail.ru

We used alimentary obesity-induced insulin resistance (IR) model in rats to investigate the influence of N-stearoylethanolamine on the content of phospholipids and their fatty acid composition.  Our results show that prolonged high-fat diet triggers considerable aberrations in the composition of main phospholipids in the liver and can be one of the causes of IR in rats. In particular, the increase of phosphatidylcholine, phosphatidylethanolamine and significant decrease of other phospholipids: lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and diphosphaglicerol were observed. The levels of monounsaturated (erucic, nervonic, oleic) and polyunsaturated (eicosatrienoic, docosatrienoic, arachidonic) fatty acids were increased; meanwhile the content of diunsaturated acids was decreased.  The NSE administration (50 mg/kg of body weight) caused restoration of the phospholipids content in the liver of rats with diet-induced IR that highly correlated with the decrease in plasma insulin level and the improvement of insulin sensitivity. Moreover, the effect of NSE was accompanied by the normalization of fatty acids composition of phospholipids that could be related to modulating influen­ce of NSE on the activity of the main fatty acid desaturases.  It is known that the imbalance in phospholipid composition of the rat liver causes substantial metabolic alterations that are associated with the development of IR. Accordingly, the compensations of the imbalance by NSE can help to restore insulin sensitivity, inhibit the development of obesity, IR and type 2 diabetes.