Studies involving the GH-IGF axis: Lessons from IGF-I and IGF-I receptor gene targeting mouse models.

Abstract:

:The IGFs are ubiquitous and have pleoitropic effects. They are critical for normal growth and development, and for normal functioning of adult tissues. A liver-specific gene-deletion knockout of the IGF-I gene resulted in a mouse model with reduced circulating IGF-I levels, that led to insulin resistance due to the secondary elevation of circulating GH levels. The reduction in circulating IGF-I levels was also associated with a reduction in cancer growth and metastases in three cancer models, one for colon cancer and two for breast cancer. A second mouse model, using the transgenic approach, inhibited the IGF-I and insulin receptor function in skeletal muscle, and resulted in severe insulin resistance in muscle followed by insulin resistance in fat and liver and, eventually, beta-cell dysfunction and development of Type 2 diabetes. This progression from insulin resistance to Type 2 diabetes was most likely due to lipotoxicity with elevated serum and tissue triglyceride levels. Evidence supporting the hypothesis came from the use of fibrates and leptin injections, each of which enhanced fatty acid (FA) oxidation in liver and muscle and was associated with a reversal of the insulin resistance and diabetes.

journal_name

J Endocrinol Invest

authors

Yakar S,Pennisi P,Kim CH,Zhao H,Toyoshima Y,Gavrilova O,LeRoith D

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

19-22

issue

5 Suppl

eissn

0391-4097

issn

1720-8386

journal_volume

28

pub_type

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