A new glycotoxins inhibitor attenuates insulin resistance in liver and fat cells
- Resource Type
- Authors
- Uzma Rasool Mughal; Aneela Karim; Meha Fatima Aftab; Safina Ghaffar; Shabbir Khan Afridi; Rizwana S. Waraich; Munazza Murtaza; Khalid Mohammed Khan
- Source
- Biochemical and Biophysical Research Communications. 476:188-195
- Subject
- Glycation End Products, Advanced
Isatin
0301 basic medicine
medicine.medical_specialty
Protein Kinase C-alpha
Insulin Receptor Substrate Proteins
medicine.medical_treatment
Biophysics
030209 endocrinology & metabolism
Biochemistry
Glycogen Synthase Kinase 3
Mice
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Glycation
3T3-L1 Cells
Internal medicine
Insulin receptor substrate
Adipocytes
medicine
Animals
Humans
Insulin
Phosphorylation
Glycogen synthase
Molecular Biology
Protein kinase B
Cell Proliferation
biology
Hep G2 Cells
Cell Biology
medicine.disease
Enzyme Activation
Insulin receptor
Glucose
030104 developmental biology
Endocrinology
Liver
Hepatocytes
biology.protein
Insulin Resistance
Reactive Oxygen Species
- Language
- ISSN
- 0006-291X
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-α. 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.