Carpachromene ameliorates insulin resistance in HepG2 cells via modulating IR/ IRS1/PI3k/Akt/GSK3/FoxO1 pathway

Carpachromene ameliorates insulin resistance in HepG2 cells via modulating IR/ IRS1/PI3k/Akt/GSK3/FoxO1 pathway

31^st International Conference on DIABETES AND ENDOCRINOLOGY
February 06, 2023 | Webinar

Ahmed E Allam, Iman A.M. Abdel-Rahman, Heba Ali Hassan, Nancy Youssef, Rania Alaaeldin, Sayed F Abdelwahab, Qing-Li Zhao and Moustafa Fathy

Al-Azhar University, Egypt
South Valley University, Egypt
Sohag University, Egypt
Minia University, Egypt
Deraya University, Egypt
Taif University, Saudi Arabia
University of Toyama, Japan

Scientific Tracks Abstracts : J Diabetol

Abstract:

Insulin resistance contributes to several disorders including type 2 diabetes and cardiovascular diseases. Carpachromene is a natural active compound that inhibits α- glucosidase enzyme. The aim of the present study is to investigate the potential activity of carpachromene on glucose consumption, metabolism and insulin signaling in a HepG2 cells insulin resistant model. A HepG2 insulin resistant cell model (HepG2/IRM) was established. Cell viability assay of HepG2/ IRM cells was performed after carpachromene/metformin treatment. Glucose concentration and glycogen content were determined. Western blot analysis of insulin receptor, IRS1, IRS2, PI3k, Akt, GSK3, FoxO1 proteins after carpachromene treatment was performed. Phosphoenolpyruvate Carboxykinase (PEPCK) and Hexokinase (HK) enzymes activity was also estimated. Viability of HepG2/IRM cells was over 90% after carpachromene treatment at concentrations 6.3, 10 and 20μg/mL. Treatment of HepG2/IRM cells with carpachromene decreased glucose concentration in a concentration- and time dependent manner. In addition, carpachromene increased glycogen content of HepG2/IRM cells. Moreover, carpachromene treatment of HepG2/IRM cells significantly increased the expression of phosphorylated/total ratios of IR, IRS1, PI3K, Akt, GSK3 and FoxO1 proteins. Furthermore, PEPCK enzyme activity was significantly decreased and HK enzyme activity was significantly increased after carpachromene treatment. The present study examined, for the first time, the potential antidiabetic activity of carpachromene on a biochemical and molecular basis. It increased the expression ratio of insulin receptor and IRS1 which further phosphorylated/ activated PI3K/Akt pathway and phosphorylated/ inhibited GSK3 and FoxO1 proteins. Our findings revealed that carpachromene showed central molecular regulation of glucose metabolism and insulin signaling via IR/IRS1/ PI3K/ Akt/GSK3/FoxO1 pathway. Recent Publications 1. Ahmed Ashour, Ahmed Elbermawi, Yhiya Amen, Ahmed E. Allam, Hiromi Ikeda, Maki Nagata, Kenta Kumagae, Tomoyo Azuma, Aya Taguchi, Takuya Takemoto, Masako Matsumoto and Kuniyoshi Shimizu. Melanin Synthesis Inhibition Activity of Compounds Isolated from Bamboo Shoot Skin (Phyllostachys pubescens). Molecules 2023, 28, 23. 2. Rania Alaaeldin, Heba Ali Hassan, Islam M. Abdel-Rahman, Reham H. Mohyeldin, Nancy Youssef, Ahmed E. Allam , Sayed F. Abdelwaha, Qing-Li Zhao and Moustafa Fathy. A New EGFR Inhibitor from Ficus benghalensis Exerted Potential AntiInflammatory Activity via Akt/PI3K Pathway Inhibition. Curr. Issues Mol. Biol. 2022, 44(7), 2967-2981; 3. Heba Ali Hassan, Ahmed R. Hassan, Eslam A.R. Mohamed, Ahmad AlKhdhairawi, Hala E. Taha, Hanan M. El-Tantawy, Iman A. M. Abdel-Rahman, Ali E. Raslan, Khaled S. Allemailem, Ahmad Almatroudi, Faris Alrumaihi, Maha Ahmed Alshiekheid, Hafiz Muzzammel Rehman, Mahmoud M. Abdelhamid, Islam M. Abdel-Rahman and Ahmed E. Allam. Targeting natural plant metabolites for Hunting SARS-CoV-2 Omicron BA.1 Variant Inhibitors: Extraction, Molecular docking, Molecular dynamics and Physicochemical Properties Study. Curr. Issues Mol. Biol. 2022, 44, 5028– 5047.

Biography:

Ahmed Ezzaldean Abdellah Allam completed his Ph.D. in pharmacognosy and chemistry of natural products at the graduate school of natural science and technology, Kanazawa University, Kakuma-machi, Kanazawa, Japan. Then he completed his postdoctoral fellowship in the laboratory of systemic forest and forest product sciences, department of agro-environmental science, faculty of agriculture, Kyushu University, Japan from April 2016 to October 2017. He is currently working as an associate professor in Al-Azhar University, Egypt

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