Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans.
NIDDM is characterized by progressive insulin resistance and the failure of insulin-producing pancreatic beta cells to compensate for this resistance. Hyperinsulinemia, inflammation, and prolonged activation of the insulin receptor (INSR) have been shown to induce insulin resistance by decreasing INSR substrate (IRS) protein levels. Here we describe a role for SOCS7 in regulating insulin signaling. Socs7-deficient mice exhibited lower glucose levels and prolonged hypoglycemia during an insulin tolerance test and increased glucose clearance in a glucose tolerance test. Six-month-old Socs7-deficient mice exhibited increased growth of pancreatic islets with mildly increased fasting insulin levels and hypoglycemia. These defects correlated with increased IRS protein levels and enhanced insulin action in cells lacking SOCS7. Additionally, SOCS7 associated with the INSR and IRS1--molecules that are essential for normal regulation of insulin action. These data suggest that SOCS7 is a potent regulator of glucose homeostasis and insulin signaling.
Banks
Alexander S
AS
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Li
Jianze
J
McKeag
Lisa
L
Hribal
Marta L
ML
Kashiwada
Masaki
M
Accili
Domenico
D
Rothman
Paul B
PB
D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology; D005260:Female; D018390:Gene Targeting; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C506118:SOCS7 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D011972:Receptor, Insulin; D005947:Glucose