Liver-specific IGF-I gene deficient mice exhibit accelerated diabetes in response to streptozotocin, associated with early onset of insulin resistance

Rong Yu, Shoshana Yakar, Ye Lauren Liu, Yarong Lu, Derek LeRoith, Dengshun Miao, Jun Li Liu

Research output: Contribution to journalArticle

Abstract

Liver-specific IGF-I gene deficient (LID) mice exhibit pancreatic islet hyperplasia and insulin resistance. To clarify their causal relationship, we studied age-dependent changes in these two aspects and the response to β-cell damage caused by streptozotocin in adult mice. As a result, the onset of insulin resistance in LID mice was detectable as early as 1-month of age, while hyperinsulinemia was developed after a significant delay at 2.5-month. Upon streptozotocin administration, control mice exhibited significant hyperglycemia after 9 days, and glucose levels continued to rise at 12-15 days. LID mice developed diabetes much more rapidly, with hyperglycemia after 6 days and higher glucose levels up to 15 days. They also exhibited significant weight loss and 6/19 died. Serum insulin assay, insulin mRNA analysis and immunohistochemistry revealed that the more severe diabetes in LID mice was not due to more damage to their β-cells. Thus LID mice are more sensitive to streptozotocin-induced β-cell damage, due to a primary defect in insulin responsiveness. The pancreatic islet hyperplasia observed in these mice seems to represent a compensatory response to insulin resistance, therefore, offers no protection against β-cell damage.

Original languageEnglish (US)
Pages (from-to)31-42
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume204
Issue number1-2
DOIs
StatePublished - Jun 30 2003

Fingerprint

Streptozocin
Medical problems
Insulin-Like Growth Factor I
Liver
Insulin Resistance
Genes
Insulin
Cells
Islets of Langerhans
Hyperglycemia
Hyperplasia
Glucose
Cytoprotection
Assays
Hyperinsulinism
Weight Loss
Messenger RNA
Defects
Immunohistochemistry
Serum

Keywords

  • Cre/loxP
  • Immunohistochemistry
  • Insulin resistance
  • Pancreatic islets

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Liver-specific IGF-I gene deficient mice exhibit accelerated diabetes in response to streptozotocin, associated with early onset of insulin resistance. / Yu, Rong; Yakar, Shoshana; Liu, Ye Lauren; Lu, Yarong; LeRoith, Derek; Miao, Dengshun; Liu, Jun Li.

In: Molecular and Cellular Endocrinology, Vol. 204, No. 1-2, 30.06.2003, p. 31-42.

Research output: Contribution to journalArticle

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