Tag Archives: diabetes

The effects of endurance training and estrogen-related receptor α disruption on mitofusin 1 and 2, GLUT2, PPARβ/δ and SCD1 expression in the liver of diabetic rats

B. Shahouzehi1,2, Y. Masoumi-Ardakani3, H. Fallah4, S. Aminizadeh3*

1Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
2Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
3Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
4Department of Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
*e-mail: soheilaminizadeh@gmail.com

Received: 19 March 2020; Accepted: 13 November 2020

Diabetes is a progressive and metabolic disease with a high prevalence throughout the world. Physical activity is considered as an intervention to improve diabetes. Intervention such as estrogen-related receptor α (ERRα) inhibition is considered as a new way to manage diabetes. In current study, we examined ERRα inhibition along with exercise training (ET) on the gene expression of mitofusin 1 (MFN1), MFN2, glucose transporter 2 (GLUT2), peroxisome proliferator-activated receptor beta or delta (PPARβ/δ), and stearoyl-CoA desaturase 1 (SCD1) in rat liver. The animals were divided into 8 groups (n = 7); 1, Control (CTL) 2, Diabetes (D) 3, ERRα inhibition (ERRI) 4, Endurance Training (ET) 5, Diabetes+ERRα inhibition (D+ERRI) 6, Diabetes+Endurance training (D+ET) 7, Endurance Training +ERRα inhibition (ET+ERRI) 8, Diabetes+Endurance Training+ERRα inhibition (D+ET+ERRI). The liver tissues were used for Real-Time PCR. The results showed that ET significantly increased PPARδ, MFN1 and, MFN2 expression in control rats compared to DM group. In ERRI group, SCD1, GLUT2, MFN1 and MFN2 gene expression was increased compared to CTL and D group. In CTL and D rats, the combination of ERRα inhibition and ET significantly and additively increased MFN1, MFN2, and GLUT2 expression. Overall­, the combination of ET and ERRα inhibition probably can be considered as a potential therapeutic intervention for treatment of metabolic diseases including diabetes and cardiovascular disease.

Changes in gene expression of lactate carriers (MCT1 and CD147) in cardiac muscle of diabetic male rats: the effect of dichloroacetate and endurance training

H. Rezaeinasab1*, A. Habibi1, M. Nikbakht1, M. Rashno2,3, S. Shakerian1

1Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran;
2Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;
3Department of Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
e-mail: hamed.rezaei2020@gmail.com

Received: 23 March 2020; Accepted: 25 June 2020

Lactate accumulation can activate the pathways of mitochondrial biogenesis in the heart muscle. The purpose of this study was to investigate the effects of Pyruvate Dehydrogenase Kinase 4 (PDK4) inhibition and endurance training on the gene expression of lactate carriers (MCT1 and CD147) in the cardiac muscle of STZ-diabetic rats. In this experimental study, 64 male Wistar rats were selected and randomly divided into eight groups after induction of diabetes with streptozotocin (STZ). The endurance training protocol was performed on a treadmill for 6 weeks. Intraperitoneal injection of DCA of 50 mg/ kg body weight was used for the inhibition of PDK4 in the myocardium. Gene expression were measured using real-time PCR. The two-way ANOVA test was used to analyze the data. The results of the study showed that after endurance training, the expression of MCT1, PDK4, and CD147 genes increased significantly in line with each other (P < 0.05), and by inhibition of PDK4 in the heart muscle, the expression of MCT1 and CD147 genes in the endurance training group + diabetes + DCA and in the diabetes group + DCA decreased significantly (P < 0.05). According to the results of this study, it can be concluded that the repeated accumulation of lactate caused by exercise training in diabetic patients decrease through mitochondrial adaptation by DCA injection and subsequently oxidative stress can be reduced in cardiac tissue of diabetic patients and heart efficacy can be increased.

L-carnitine administration effects on AMPK, APPL1 and PPARγ genes expression in the liver and serum adiponectin levels and HOMA-IR in type 2 diabetes rat model induced by STZ and nicotinamide

B. Shahouzehi1,2, H. Fallah3, Y. Masoumi-Ardakani4*

1Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran;
2Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
3Department of Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
4Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
*e-mail: ymab125@gmail.com

Received: 18 January 2020; Accepted: 25 June 2020

Diabetes is a chronic disease and a public health problem globally. L-Carnitine is synthesized in the liver, promotes fatty acids oxidation and currently is used as a supplement against weight gain. Carnitine level is found to be reduced in diabetic patients and to be beneficial as a supplement at diabetes, but the mechanisms­ of this effect is not fully understood. Therefore, we evaluated the oral L-carnitine supplementation on expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPARγ), adaptor protein APPL1 genes in the liver and insulin and adiponectin levels  in the serum of diabetic rats. Rats were randomly divided into three groups (n = 8) as follow: group 1 – control without any treatment, group 2 – diabetic control rats which received STZ (45 mg/kg) and nicotinamide (200 mg/kg) by i.p. injection, group 3 – diabetic rats which received 600 mg/kg/day carnitine orally for 35 days. It was found that L-carnitine supplementation reduced the level of fasting glucose compared to that in control and diabetic groups (P = 0.001,  P = 0.0001 respectively) and increased adiponectin level compared to diabetic nontreated rats (P = 0.0001). Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly increased in the diabetic group and reduced in the group that received L-carnitine. These promising beneficial effect of L-carnitine on the type 2 diabetes in rats’ model was shown to be conducted through the up-regulation of AMPK, PPARγ and APPL1 genes expression in the liver and elevation of serum adiponectin level.

Biochemical mechanisms of chromium action in the human and animal organism

R. Ya. Iskra, V. G. Yanovych

Institute of Animal Biology, National Academy of Agrarian Sciences, Lviv, Ukraine;
e-mail: ruslana_iskra@inenbiol.com.ua

Modern data concerning biologic characteristics of chromium (Cr3+) its placement in nature, accessibility and metabolic action of its different forms in humans and animals is presented in this survey. Essentiality of chromium for humans is emphasized, data about consumption norms of this microelement and its use for curing different diseases especially diabetes mellitus and atherosclerosis of vessels are presented. The biochemical mechanisms of Cr3+ effect on the metabolism in the human and animal organism are analyzed. It is shown that the organism reacts to chrome additions by the change of some metabolism links. Chrome influences positively growth and development of foetus, stimulates metabolism of glucose and insulin in the humans and animals. However, at the set chromium requirements it is necessary to take into account its low availability in food, high release of Cr3+ from the organism under the influence of stress factors, considerable decline of its level with age, and also in the period of pregnancy and lactation. Therefore experimental researches of introduction of Cr3+ additions to the diet of people and forage of animals taking into account their body mass, age and clinical state, can explain the biochemical mechanisms of biological action of this microelement.

Biological effects of lithium – fundamental and medical aspects

A. S. Mikosha, O. I. Kovzun, M. D. Tronko

State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
e-mail: asmikosha@gmail.com

In this review, the authors present data on the biological effects of lithium in human and animal body and the subsequent manifestations of these effects. Since the lithium ion radius is close to that of magnesium, lithium ion can compete with magnesium as cofactor of certain magnesium-dependent enzymes. Numerous studies have shown lithium to be an inhibitor of glycogen synthase kinase 3. It also inhibits the phosphatases involved in the metabolism of phosphoinositides and phosphoadenylate 3′-nucleotidase. As these enzymes play an important and sometimes crucial role in signaling systems activity, lithium is able to affect the essential physiological, adaptive and pathogenetic processes.

Cytochrome P450 2E1 participation in the pathogenesis of experimental metabolic syndrome in guinea pigs

V. V. Rushchak, M. O. Chashchyn

Institute of Molecular Biology and Genetics, National Academy
of Sciences of Ukraine, Kyiv;
e-mail: v.v.rushchak@gmail.com

In this work the experimental metabolic syndrome on the basis of protamine sulfate modeling in guinea pigs was reproduced and pathological processes in the liver of experimental animals were studied. We determined the level of free radicals and markers of liver damage in the blood of experimental animals. We investigated the liver glycogen content and K+,Na+-ATPase activity in the liver of experimental animals as well as measured the cytochrome P450 2E1 (CYP2E1) expression – one of the main factors of oxidative stress. Evidence of development of hepatotoxic processes, increasing of the CYP2E1 level as well as of the free radical level in the animals with metabolic syndrome were found. Using of CYP2E1 inhibitors had shown that the free radical level in the blood of experimental animals depended on the level of the enzyme expression and activity. The obtained results suggest that the changes in the CYP2E1 expression play an important role in the development of hepatotoxic processes upon experimental metabolic syndrome. It was assumed that pharmacological correction of the enzyme expression may be an important mechanism for the influence on the metabolic syndrome clinical course.

The history of creation and study of vitamin D medicines in the Laboratory of Medical Biochemistry of the Palladin Institute of Biochemistry of the NAS of Ukraine for 1990-2015

N. E. Lugovska, G. G. Lugovska, I. G. Chernysh, S. P. Yurasova, V. M. Danilova

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: tto@biochem.kiev.ua

The article presents the main results of inventive activity of the Laboratory of Medical Biochemistry headed by Dr. L. I. Apukhovska of the Palladin Institute of Biochemistry of the NAS of Ukraine. These researches continued the works initiated by Prof. V. P. Vendt and included development of technologies for the production of highly efficient preparations based on vitamin D3, namely “VIDEIN” in several modified forms (for prevention and treatment of rickets and rickets-like diseases in children, osteopathy of various origins, hypovitaminosis D in pregnant, mineral metabolism disorders, etc), water-soluble vitamin D3 (for prevention and treatment of rickets in children from the first months of life), “KALMIVID” and ”KALMIVID-M” (for treatment of bone tissue diseases associated with mineral metabolism disorders), the pharmaceutical composition “MEBIVID” (for treatment of osteoporosis and diseases associated with reduced bone mineral density) and therapeutic vitamin-D3-E protein complex (for regulation of metabolic processes, improvement of structural and functional bone quality as well as structure and function of epiphyseal cartilage). All products are characterized by stability of vitamin D3 molecule, and thus, dosing accuracy and reliability, whilst not containing toxic preservatives and stabilizers. The technologies for production as well as analytical and normative documentations have been developed for all preparations.

Calpains: general characteristics and role in various states of the organism

N. F. Starodub1, L. M. Samokhina2, S. N. Koval2, I. A. Snegurskaya2

1National University of Life and Environmental Sciences of Ukraine, Kyiv;
e-mail: nikstarodub@yahoo.com;
2GD L. T. Malaya National Institute of Therapy of NAMS of Ukraine, Kharkov;
e-mail: lub.samokhina@yandex.ua

Calpains are a family of cytoplasmic calcium-dependent proteinases with papain-like activity. They participate in a variety of processes in the body: age changes, functioning of endothelium and pulmonary system, regulation of apoptosis and necrosis, development of various hypometabolic states, arterial hypertension, diabetes and chronic kidney disease, tumor growth. It is concluded that calpains, causing limited proteolysis of substrates, play an important role in a wide range of biological phenome­na. Their activity is associated with the response to the calcium-dependent signaling and the effects of aging. Inhibition of calpains activity contributes to inhibition of endothelial dysfunction, cardiovascular disease, formation of structural and functional changes in the kidney tissue, has neuroprotective effect, preventing sarcopenia, reduces inflammatory reactions caused by hyperventilation of the lungs.