Table 1

Insulin resistance 'subphenotypes' seen in humans and mice with deficiency or mutations of HMGA1 or INSR*

Human

Mouse


Tissue

Characteristic

INSR mutation

HMGA1 mutation

Common IR/T2DM

Hmga1-/-

Insr loss of function


Whole body

Fasting glucose

↓ to → to ↑

↓ to → to ↑

→ to ↑

↓ to → to ↑

Fasting insulin

↑↑↑

↑↑↑

↑ to ↑↑

↑↑

Insulin sensitivity

↓↓↓

↓↓↓

↓ to ↓↓

↓↓↓

Glucose tolerance

→ to ↓

→ to ↓

→ to ↓

Liver

Lipid profile

Normal Tg and HDL

?

High Tg, low HDL

?

?

IGFBP1

↑↑

SHBG

?

?

?

Liver fat

Normal

?

?

?

Adipose tissue

Adiponectin

↑↑

?

?

Leptin

?

→ to ↑↑

?

RBP

?

↓↓

?


*Tg, triglyceride; HDL, high density lipoprotein cholesterol; IGFBP1, insulin-like growth factor binding protein 1; SHBG, sex hormone binding globulin; RBP, retinol binding protein. Representative of patients with Rabson Mendenhall syndrome, in which there is approximately 90% loss of INSR function. No strictly Insr hypomorphic mice with 10% residual receptor function have been reported, so results are inferred from related models, such as a conditional peripheral Insr knockout and an Insr mosaic knockout.

Semple Journal of Biology 2009 8:64   doi:10.1186/jbiol164