TY - JOUR
T1 - Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory β-cell hyperplasia
AU - Kubota, Naoto
AU - Tobe, Kazuyuki
AU - Terauchi, Yasuo
AU - Eto, Kazuhiro
AU - Yamauchi, Toshimasa
AU - Suzuki, Ryo
AU - Tsubamoto, Yoshiharu
AU - Komeda, Kajuro
AU - Nakano, Ryosuke
AU - Miki, Hiroshi
AU - Satoh, Shinobu
AU - Sekihara, Hisahiko
AU - Sciacchitano, Salvatore
AU - Lesniak, Maxine
AU - Aizawa, Shinichi
AU - Nagai, Ryozo
AU - Kimura, Satoshi
AU - Akanuma, Yasuo
AU - Taylor, Simeon I.
AU - Kadowaki, Takashi
PY - 2000
Y1 - 2000
N2 - To investigate the role of insulin receptor substrate (IRS)-2 in vivo, we generated IRS-2-deficient mice by gene targeting. Although homozygous IRS-2-deficient mice (IRS-2(-/-) mice) had a body weight similar to wild-type mice, they progressively developed type 2 diabetes at 10 weeks. IRS-2(-/-) mice showed insulin resistance and a defect in the insulin-stimulated signaling pathway in liver but not in skeletal muscle. Despite insulin resistance, the amount of β-cells was reduced to 83% of that in wild-type mice, which was in marked contrast to the 85% increase in the amount of β-cells in IRS-1-deficient mice (IRS-1(-/-) mice) to compensate for insulin resistance. Thus, IRS-2 plays a crucial role in the regulation of β-cell mass. On the other hand, insulin secretion by the same number of cells in response to glucose measured ex vivo was significantly increased in IRS-2(-/-) mice compared with wild-type mice but was decreased in IRS-1(-/-) mice. These results suggest that IRS-1 and IRS-2 may play different roles in the regulation of β-cell mass and the function of individual β-cells.
AB - To investigate the role of insulin receptor substrate (IRS)-2 in vivo, we generated IRS-2-deficient mice by gene targeting. Although homozygous IRS-2-deficient mice (IRS-2(-/-) mice) had a body weight similar to wild-type mice, they progressively developed type 2 diabetes at 10 weeks. IRS-2(-/-) mice showed insulin resistance and a defect in the insulin-stimulated signaling pathway in liver but not in skeletal muscle. Despite insulin resistance, the amount of β-cells was reduced to 83% of that in wild-type mice, which was in marked contrast to the 85% increase in the amount of β-cells in IRS-1-deficient mice (IRS-1(-/-) mice) to compensate for insulin resistance. Thus, IRS-2 plays a crucial role in the regulation of β-cell mass. On the other hand, insulin secretion by the same number of cells in response to glucose measured ex vivo was significantly increased in IRS-2(-/-) mice compared with wild-type mice but was decreased in IRS-1(-/-) mice. These results suggest that IRS-1 and IRS-2 may play different roles in the regulation of β-cell mass and the function of individual β-cells.
UR - http://www.scopus.com/inward/record.url?scp=0033755408&partnerID=8YFLogxK
U2 - 10.2337/diabetes.49.11.1880
DO - 10.2337/diabetes.49.11.1880
M3 - 学術論文
C2 - 11078455
AN - SCOPUS:0033755408
SN - 0012-1797
VL - 49
SP - 1880
EP - 1889
JO - Diabetes
JF - Diabetes
IS - 11
ER -