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* The Lundberg Laboratory for Diabetes Research and
SOS Obesity Research Laboratory, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden; and
Department of Endocrinology, Lund University, Malmö University Hospital, Malmö, Sweden
1Correspondence: The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Göteborg, Sweden. E-mail ulf.smith{at}medicine.gu.se
We examined the gene and protein expression of IRS 1 (insulin receptor
substrate 1) in adipocytes from two groups of healthy individuals with
an increased propensity for non-insulin-dependent diabetes mellitus
(NIDDM): those with two first-degree relatives with diabetes and
another group with massive obesity. A low expression of IRS 1 (
50%
of the matched control group) was seen in 
30% of both groups and
these individuals were characterized by insulin resistance and its
hallmarks: higher levels of insulin, glucose, and triglycerides. Two
individuals with previously unknown NIDDM were diagnosed and both had
low IRS 1 expression. Low IRS 1 protein expression was associated with
low mRNA levels but not with the common Gly972Arg polymorphism of the
IRS 1 gene. Taken together, our present and previous findings show that
a low expression of IRS 1 in fat cells predicts insulin resistance and
NIDDM. Furthermore, they support the likelihood that an impaired
transcriptional activation may play a key role in the pathogenesis of
NIDDM.—Carvalho, E., Jansson, P.-A., Axelsen, M., Eriksson, J. W., Huang, X., Groop, L., Rondinone, C., Sjöström, L.,
Smith, U. Low cellular IRS 1 gene and protein expression predict
insulin resistance and NIDDM.
Key Words: diabetes • obesity • insulin receptor substrate 1 • insulin signaling • insulin action
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