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4-Hydroxyisoleucine Ameliorates Fatty Acid-Induced Insulin Resistance and Inflammatory Response in Skeletal Muscle Cells

4-Hydroxyisoleucine Ameliorates Fatty Acid-Induced Insulin Resistance and Inflammatory Response in Skeletal Muscle Cells

Chandan Kumar Maurya, Rohit Singh, Natasha Jaiswal, K Venkateswarlu, Tadigoppula Narender, Akhilesh Kumar Tamrakar

Mol Cell Endocrinol. 2014 Sep;395(1-2):51-60.

PMID: 25109277

Abstract:

The 4-hydroxyisoleucine (4-HIL), an unusual amino acid isolated from the seeds of Trigonella foenum-graecum was investigated for its metabolic effects to ameliorate free fatty acid-induced insulin resistance in skeletal muscle cells. An incubation of L6 myotubes with palmitate inhibited insulin stimulated-glucose uptake and -translocation of glucose transporter 4 (GLUT4) to the cell surface. Addition of 4-HIL strongly prevented this inhibition. We then examined the insulin signaling pathway, where 4-HIL effectively inhibited the ability of palmitate to reduce insulin-stimulated phosphorylation of insulin receptor substrate-1 (IRS-1), protein kinase B (PKB/AKT), AKT substrate of 160 kD (AS160) and glycogen synthase kinase 3β (GSK-3β) in L6 myotubes. Moreover, 4-HIL presented strong inhibition on palmitate-induced production of reactive oxygen species (ROS) and associated inflammation, as the activation of NF-κB, JNK1/2, ERK1/2 and p38 MAPK was greatly reduced. 4-HIL also inhibited inflammation-stimulated IRS-1 serine phosphorylation and restored insulin-stimulated IRS-1 tyrosine phosphorylation in the presence of palmitate, leading to enhanced insulin sensitivity. These findings suggested that 4-HIL could inhibit palmitate-induced, ROS-associated inflammation and restored insulin sensitivity through regulating IRS-1 function.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP781658239	4-Hydroxyisoleucine		781658-23-9	Price

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