Tag Archives: AMPK
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.
The effects of PDK4 inhibition on AMPK protein levels and PGC-1α gene expression following endurance training in skeletal muscle of Wistar rats
S. Aminizadeh1, Y. Masoumi-Ardakani1, B. Shahouzehi2
1Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Iran;
e-mail: soheilaminizadeh@gmail.com; ymab125@yahoo.com;
2Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Iran;
e-mail: bshahouzehi@gmail.com
There are regulatory networks in cells which surveil the physiological and environmental states. These cellular regulations are conducted through gene expression modulation. Skeletal muscle is able to adapt shortly and produce ATP at different conditions. AMPK (AMP-activated protein kinase) and PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) are important regulators of cellular energy homeostasis. We designed this study to examine the effects of interactions between endurance training and PDK4 (pyruvate dehydrogenase kinase 4) inhibition on AMPK and PGC-1α expression in rat skeletal muscle. Thirty-two male Wistar rats were randomly selected and divided into 4 groups (n = 8); Group 1 control which did not receive any treatment, Group 2 received dichloroacetic acid (DCA) (150 mg/kg/day), Group 3 (endurance training group), Group 4 which received DCA and performed endurance training. AMPK protein expression, PDK4 and PGC-1α gene expression were measured by western blotting and real-time PCR, respectively. Our data showed that PDK4 inhibition caused AMPK protein elevation. Endurance training (group 2) and PDK4 inhibition (group 4) induce significant enhancement of PGC-1α gene expression compared to control group. The group which received DCA showed significant elevation of PDK4 gene expression compared to control group (P = 0.001), also other two groups (groups 2 & 3) showed significant elevation of PDK4 gene expression compared to control (P = 0.006). It seems that the combination of endurance training and PDK4 inhibition by up-regulation of PGC-1α expression, effectively improves energy state and performance in skeletal muscle.
Effect of L-carnitine administration on serum insulin and adiponectin levels, and AMPK, APPL1 and PPARγ gene expression in STZ-induced diabetic rat liver
B. Shahouzehi1, K. Barkhordari2, S. Aminizadeh3, Y. Masoumi-Ardakani4*
1Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Iran;
e-mail: bshahouzehi@yahoo.com;
2Department of Virology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
e-mail: khabatzanbil@gmail.com;
3Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Iran;
e-mail: soheilaminizadeh@gmail.com;
4Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Iran;
*e-mail: ymab125@yahoo.com
Diabetes is considered as a metabolic disease in which insulin secretion and functions are disturbed and characterized by hyperglycemia. L-carnitine is synthesized in most mammals and plays critical role in fatty acid oxidation and energy production. Data about the L-carnitine hypoglycemic effects are controversial. We evaluated long-term oral L-carnitine administration effects on blood glucose, insulin and adiponectin levels, as well as expression of AMPK, APPL1 and PPARγ genes in liver of STZ-induced diabetic rats. Group 1 (control), did not receive any treatment, group 2 received 50 mg/kg STZ by i.p injection, group 3 received single dose of 50 mg/kg STZ by i.p injection and also 600 mg/kg/day L-carnitine orally for 5 weeks. Our results showed that L-carnitine long-term oral supplementation significantly reduced blood glucose and normalized insulin levels in diabetic rats. Also, we found that L-carnitine significantly increased AMPK and APPL1 expression, and showed a mild elevation of PPARγ expression. In sum, we suggest that long-term L-carnitine supplementation has beneficial effects on diabetic rats which showed hypoglycemic effects. Probably the beneficial effects of L-carnitine are contributed to the upregulation of insulin sensitizers such as AMPK and adiponectin.