TY - JOUR
T1 - Liver-specific IGF-I gene deficient mice exhibit accelerated diabetes in response to streptozotocin, associated with early onset of insulin resistance
AU - Yu, Rong
AU - Yakar, Shoshana
AU - Liu, Ye Lauren
AU - Lu, Yarong
AU - LeRoith, Derek
AU - Miao, Dengshun
AU - Liu, Jun Li
PY - 2003/6/30
Y1 - 2003/6/30
N2 - 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.
AB - 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.
KW - Cre/loxP
KW - Immunohistochemistry
KW - Insulin resistance
KW - Pancreatic islets
UR - http://www.scopus.com/inward/record.url?scp=0038106699&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038106699&partnerID=8YFLogxK
U2 - 10.1016/S0303-7207(03)00145-X
DO - 10.1016/S0303-7207(03)00145-X
M3 - Article
C2 - 12850279
AN - SCOPUS:0038106699
VL - 204
SP - 31
EP - 42
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -