Partners in diabetes epidemic: A global perspective

Table 1 The important physiological dysfunction negatively affect insulin synthesis and secretion

Defect	Phenomenon	Ref.
β cells failure	Insulin resistance, hyperglycaemia	Kahn[20]
↓ GLUT 4 translocation in adipocytes	↓ IRS-1 expression, ↓ PIP-3-kinase and PKB/Akt activities	Wilcox[23], Smith[24]
↑ Plasma free fatty acid	Insulin resistance, ↓ lipoprotein lipase activity, hypertriglyceridaemia	Reaven et al[26], Frayne[27]
Suppression of GLUT4 activity (muscle and liver)	Insulin dysfunction	Leroith et al[33]
Suppression of insulin receptor activity (LIRKO) (liver)	Hyperinsulinemia, hepatic and peripheral insulin resistance, glucose intolerance, insulin dysfunction	Michael et al[37]
Nuclear receptor translocator (ARNT)	↓ Insulin secretion, alterations in gene expression	Gunton et al[47], Kewley et al[48]
Suppression of IRS-2	β-cell apoptosis, insulin resistance	Rhodes[53]

ARNT: Aryl hydrocarbon nuclear receptor translocator; LIRKO: Liver-specific insulin receptor knockout; IRS: Insulin receptor substrate.