Table 1.

Readouts of hepatic insulin resistance

Readout	Change in Insulin Resistance	Direct/Indirect	Acute/Chronic	Notes
Activation of net hepatic glycogen synthesis	↓	Direct	Acute	Requires both hyperinsulinemia and hyperglycemia.
Suppression of hepatic gluconeogenesis	↓	Indirect	Acute	Related to suppression of WAT lipolysis leading to decreased NEFA and glycerol turnover and hepatic acetyl-CoA content. There may also be a small direct effect of insulin by suppression of intrahepatic lipolysis.
Suppression of hepatic glucose production	↓	Direct and indirect	Acute	Variable contributions of gluconeogenesis and glycogenolysis depending on species and fasting duration.
INSR Tyr phosphorylation and IRK activity	↓	Direct	Acute
IRS Tyr phosphorylation	↓	Direct	Acute
AKT Ser/Thr phosphorylation	↓	Direct	Acute	Multiple inputs to Ser473 phosphorylation.
Gluconeogenic gene expression	↑	Direct	Chronic	Especially G6pc, Pck1.
De novo lipogenesis	↓	Direct	Chronic	Multiple inputs including mTORC1, ChREBP.
Fasting plasma insulin	↑	Direct and indirect	Chronic	Crude surrogate of hepatic insulin resistance, useful in large epidemiologic studies.

INSR, insulin receptor; IRK, INSR kinase; IRS, insulin receptor substrate; WAT, white adipose tissue; NEFA, nonesterified fatty acid.