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

Abstract

diabetes is a chronic disease and 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.

Metabolic Regulation of T cell Activity: Implications for Metabolic-Based T-cell Therapies for Cancer

“…LKB1 is a serine/threonine kinase that acts as a tumor suppressor and inhibits the proliferation and metabolism of cancer cells through phosphorylating and activating AMPK [ 16 ] . The LKB1-AMPK signaling pathway plays a substantial role in regulating cellular metabolism, proliferation, and survival in response to nutrients [ 17 ] . The signaling of AMPK inhibits metabolic pathways such as glycolysis [ 18 ] , glutaminolysis [ 13 ] , and lipogenesis [ 19 ] while enhances catabolic processes like mitophagy and autophagy [ 13 ] .…”