Abstract
The liver is the main organ involved in lipid metabolism process and it helps in drug detoxification. Insulin resistance is considered one of risk reasons which lead to several metabolic diseases. Currently, berberine (BER) occupies a huge challenge against multiple diseases with no toxic effect. The present work was aimed to identify, does BER-chloride has a poisonous influence on the liver? and investigating the outcome of BER-chloride on PI3K/Akt-p/SIRT-1/PTEN pathway during insulin resistance syndrome. The insulin resistance model was achieved in experimental female rats via high-fat diet (HFD). Glucose, insulin, lipid profiles, and hepatic oxidative stress parameters were assessed. PI3K, AKt-p, SIRT-1, and PTEN levels in hepatic tissue were determined at genome and protein levels. Further adiponectin concentration was performed in serum, hepatic, and white adipose tissues. Molecular study of fold alteration in insulin, insulin receptor, and retinol binding protein-4 (RBP4) in liver was done. PRACTICAL APPLICATIONS: Obesity syndrome causes multiple obstacles in modern years. The current results revealed elevation the body weight of rats, plasma glucose, homeostatic model assessment, glycated hemoglobin, insulin, and lipid profiles concentrations in a group of rats, which nourished HFD for 8 weeks and this rise, was diminished after 2 weeks from BER-chloride administration. Further, BER-chloride improved transaminases enzymes, pro-oxidant, and antioxidant defense system, PI3K, AKt-p, SIRT-1, and PTEN in the liver, with downregulation of hepatic RBP4. Hence, these data provide a crucial message that BER-chloride enhanced both hepatic function and insulin signaling pathways that might be of therapeutic importance to insulin resistance with no harmful effect on the liver. BER-chloride is predicted to be a drug of choice for obesity complications cure.
Highlights
The increased prevalence of obesity between individuals has become a serious health problem worldwide
Insulin resistance defined as a disease condition in which insulin is secreted from β-cell of pancreas but its function is impaired in peripheral tissues such as liver, adipose tissue and skeletal muscle
Enzyme linked immunoassay (ELISA) kit of insulin, PI3K, AKt-P, sirtuin type 1 (SIRT-1), phosphatase and tension homologue (PTEN) and adiponectin were purchased from DRG (USA), Wuhan Fine Biological Technology Co. (China), Ray
Summary
The increased prevalence of obesity between individuals has become a serious health problem worldwide. Β-cell of pancreas maintains the normal glucose tolerance by increasing insulin release to overcome the reduction of insulin efficiency. One of the predisposing risk factor to obesity is the amount of fat in the diet due to modern life styles. Obesity usually accompanied by insulin resistance and hyperglycemia [1]. Insulin resistance defined as a disease condition in which insulin is secreted from β-cell of pancreas but its function is impaired in peripheral tissues such as liver, adipose tissue and skeletal muscle. Insulin resistance usually associated with metabolic disorders such as hyperlipidemia, type II diabetes mellitus, non-alcoholic fatty liver and cardiovascular disease and early mortality is considered one of insulin resistance prognosis in some individuals [2].
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