Table 1.

Effects of 4-hydroxyisoleucine in insulin resistance and its adverse metabolic effects.

	Model	Experimental results	Reference
In vitro studies	Isolated human and rat pancreas	Increase of glucose-stimulated insulin secretion	[89]
	Normal and type II diabetic rats, isolated rat islets	Increased oral glucose tolerance, increased glucose-stimulated insulin secretion	[82]
	Isolated rat islets	Increased glucose-stimulated insulin secretion	[83]
	Skeletal muscle (L6 myocytes)	Increased glucose uptake, increased Akt phosphorylation on Ser 473 (pAkt), increased PI3K, increased glucose transporter 4 (GLUT4)	[103]
	Insulin-resistant skeletal muscle (L6 myocytes)	Increased insulin receptor substrate-1 tyrosine phosphorylation (pIRS-1), increased PI3K, increased pAkt, decreased reactive oxygen species (ROS), decreased NF-kB, decreased c-Jun N-terminal kinase 1/2 (JNK), decreased p38 MAPK	[104]
	Insulin-resistant 3T3-L1 adipocytes	Decreased TNF-α, increased glucose uptake	[105]
	Insulin-resistant HepG2 cells	Reduced TNF-α, stimulated expression of IRS-1 and GLUT4, inhibited expression of p-IRS-1 (Ser307)	[106]
In vivo studies	Zucker fa/fa rats, high fat + sucrose fed rats	Increased glucose tolerance, increased insulin sensitivity, reduced hepatic glucose production, increased phosphatidylinositide-3 kinase (PI3K), reduced fasting insulin	[93]
	Hamsters	Decreased serum triglycerides, decreased serum total cholesterol, decreased free fatty acids, increased HDL:TC ratio	[95]
	Type II diabetic rats	Decreased blood glucose, increased serum HDL, decreased alanine aminotransferase, decreased aspartate aminotransferase	[100]
	C57BL/db/db mice	Decreased blood glucose, decreased serum triglycerides, total cholesterol and LDL, increased serum HDL	[101]
	Type I diabetic rats	Decreased blood glucose, decreased serum total cholesterol, decreased serum LDL, decreased serum triglycerides, increased serum HDL	[102]