Insulin resistance in the liver-specific IGF-1 gene-deleted mouse is abrogated by deletion of the acid-labile subunit of the IGF-binding protein-3 complex: Relative roles of growth hormone and IGF-1 in insulin resistance

Martin Haluzik, Shoshana Yakar, Oksana Gavrilova, Jennifer Setser, Yves Boisclair, Derek LeRoith

Research output: Contribution to journalArticle

Abstract

Liver IGF-1 deficient (LID) mice demonstrate a 75% reduction in circulating IGF-1 levels and a corresponding fourfold increase in growth hormone (GH) levels. At 16 weeks of age, LID mice demonstrate, using the hyperinsulinemic-euglycemic clamp, insulin insensitivity in muscle, liver, and fat tissues. In contrast, mice with a gene deletion of the acid-labile subunit (ALSKO) demonstrate a 65% reduction in circulating IGF-1 levels, with normal GH levels and no signs of insulin resistance. To further clarify the relative roles of increased GH and decreased IGF-1 levels in the development of insulin resistance, we crossed the two mouse lines and created a double knockout mouse (LID+ ALSKO). LID+ALSKO mice demonstrate a further reduction in circulating IGF-1 levels (85%) and a concomitant 10-fold increase in GH levels. Insulin tolerance tests showed an improvement in insulin responsiveness in the LID+ALSKO mice compared with controls; LID mice were very insulin insensitive. Surprisingly, insulin sensitivity, while improved in white adipose tissue and in muscle, was unchanged in the liver. The lack of improvement in liver insulin sensitivity may reflect the absence of IGF-1 receptors or increased triglyceride levels in the liver. The present study suggests that whereas GH plays a major role in inducing insulin resistance, IGF-1 may have a direct modulatory role.

Original languageEnglish (US)
Pages (from-to)2483-2489
Number of pages7
JournalDiabetes
Volume52
Issue number10
DOIs
StatePublished - Oct 1 2003

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Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Growth Hormone
Insulin Resistance
Acids
Liver
Genes
Insulin
Muscles
White Adipose Tissue
IGF Type 1 Receptor
Glucose Clamp Technique
Gene Deletion
Knockout Mice
Triglycerides
Fats

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Insulin resistance in the liver-specific IGF-1 gene-deleted mouse is abrogated by deletion of the acid-labile subunit of the IGF-binding protein-3 complex : Relative roles of growth hormone and IGF-1 in insulin resistance. / Haluzik, Martin; Yakar, Shoshana; Gavrilova, Oksana; Setser, Jennifer; Boisclair, Yves; LeRoith, Derek.

In: Diabetes, Vol. 52, No. 10, 01.10.2003, p. 2483-2489.

Research output: Contribution to journalArticle

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