title: Liver-specific IGF-I gene deficient mice exhibit accelerated diabetes in response to streptozotocin, associated with early onset of insulin resistance.
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 beta-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 beta-cells. Thus LID mice are more sensitive to streptozotocin-induced beta-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 beta-cell damage.
authors.affiliation: Fraser Laboratories, M3-15, Department of Medicine, McGill University Health Center, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1.
authors.forename: Rong
authors.initials: R
authors.lastname: Yu
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
authors.forename: Ye Lauren
authors.initials: YL
authors.lastname: Liu
authors.forename: Yarong
authors.initials: Y
authors.lastname: Lu
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
mesh_terms: D017668:Age of Onset; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006943:Hyperglycemia; D006946:Hyperinsulinism; D006965:Hyperplasia / Q000209:etiology; D007333:Insulin Resistance / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics*; D007515:Islets of Langerhans / Q000473:pathology*; D008099:Liver; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013311:Streptozocin; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I