A new glycotoxins inhibitor attenuates insulin resistance in liver and fat cells

作者：Afridi Shabbir Khan; Aftab Meha Fatima; Murtaza Munazza; Ghaffar Safina; Karim Aneela; Mughal Uzma Rasool; Khan Khalid Mohammed; Waraich Rizwana Sanaullah^*

来源：Biochemical and Biophysical Research Communications, 2016, 476(4): 188-195.

DOI：10.1016/j.bbrc.2016.05.085

• Insulin signal transduction
• Insulin resistance
• Protein kinase
• Glycotoxins
• Schiff bases of istain
• Diabetes

Glycotoxins/Advanced glycation end products (AGES) have implications in development of diabetes and related diseases. In the present study we deciphered the mechanisms of action of URM-II-81, a new derivative of isatin, in alleviation of insulin resistance in human hepatocytes and murine adipocytes. URM-II-81 reduced AGES formation and receptor for advanced glycation end products (RAGE) expression in both cell types. We also observed suppression of methylglyoxal (MGO) mediated ROS production and deactivation of PKC-alpha. URM-II-81 restored proximal insulin signaling by modulating IRS-1 phosphorylation. URM-II-81 also alleviated MGO mediated diminished distal insulin signaling by increasing protein kinase B (PKB) and glycogen synthase kinase 3-beta (GSK-3-beta) phosphorylation. Glycogen synthesis was also increased in hepatocytes after treatment with URM-II-81. In adipocytes URM-II-81 prevented MGO induced reduced glucose uptake. We conclude that URM-II-81 can be a possible treatment target to address glycotoxins induced insulin resistance.

• 出版日期2016-8-5