A new indanedione derivative alleviates symptoms of diabetes by modulating RAGE-NF-kappaB pathway in db/db mice

Biochemical and Biophysical Research Communications
Gulnaz KhanRizwana Sanaullah Waraich

Abstract

Accumulating evidence indicates that a number of tissues are damaged due to build-up of abnormal amount of Advanced Glycation End products (AGEs) in several diseases including diabetes. Currently AGE inhibitors are scarce in clinical use indicating a need for development of new anti-AGE agents. The aim of the current study is to identify the new AGE inhibitors and to decipher their mechanism of action for alleviating symptoms of diabetes in mice. Among several derivatives, one of the derivatives of indanedione, IDD-24 demonstrated highest inhibition of AGE formation and AGE mediated reactive oxygen species production in HepG-2 and mature 3T3-L1 adipocytes. In mice treated with IDD-24, reduction in serum AGE formation and expression of Receptor for AGEs (RAGE) was seen in IDD-24 treated db/db mice. In vivo, glycogen synthesis was also increased in muscle tissue. In adipocytes, anti-AGE agent restored AGEs' induced diminished glucose uptake in fat cells. Mice treated with IDD-24 exhibited increased glucose tolerance, increaed serum adiponectin levels and decreased insulin resistance. Deciphering mechanism of IDD-24 in diabetic mice, it was observed that nuclear factor-κB (NF-κB) and serine phosphorylation of Insulin receptor subs...Continue Reading

Citations

Jan 6, 2021·Molecular and Cellular Biochemistry·Ma Eugenia Garay-SevillaArmando Rojas
May 6, 2021·Antioxidants·Aishwarya R VaidyaGiordano Pula

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