Liver-specific IGF-I gene deficient mice exhibit accelerated diabetes in response to streptozotocin, associated with early onset of insulin resistance.
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.
Yu
Rong
R
Fraser Laboratories, M3-15, Department of Medicine, McGill University Health Center, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1.
Yakar
Shoshana
S
Liu
Ye Lauren
YL
Lu
Yarong
Y
LeRoith
Derek
D
Miao
Dengshun
D
Liu
Jun-Li
JL
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
D001786:Blood Glucose; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I