Acute in vivo effects of insulin on gene expression in adipose tissue in insulin-resistant and insulin-sensitive subjects.
OBJECTIVE
We determined the response of selected genes to in vivo insulin in adipose tissue in 21 non-diabetic women.


METHODS
The women were divided into insulin-sensitive and -resistant groups based on their median whole-body insulin sensitivity (8.7+/-0.4 vs 4.2+/-0.3 mg kg(-1) min(-1) for insulin-sensitive vs -resistant group). Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 h of i.v. maintained euglycaemic hyperinsulinaemia. Adipose tissue mRNA concentrations of facilitated glucose transporter, member 1 (SLC2A1, previously known as GLUT1), facilitated glucose transporter, member 4 (SLC2A4, previously known as GLUT4), peroxisome proliferator-activated receptor gamma ( PPARG), peroxisome proliferator-activated receptor gamma co-activator 1alpha (PPARGC1A), 11beta-hydroxysteroid dehydrogenase-1 (HSD11B1), TNF, adiponectin (ADIPOQ), IL6 and the macrophage marker CD68 were measured using real-time PCR.


RESULTS
Basal expression of 'insulin-sensitivity genes' SLC2A4 and ADIPOQ was lower while that of 'insulin-resistance genes', HSD11B1 and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. Insulin significantly increased expression of 'insulin-sensitivity genes' SLC2A4, PPARG, PPARGC1A and ADIPOQ in the insulin-sensitive group, while only expression of PPARG and PPARGC1A was increased in the insulin-resistant group. The expression of 'insulin-resistance genes' HSD11B1 and IL6 was increased by insulin in the insulin-resistant group, but insulin failed to increase HSD11B1 expression in the insulin-sensitive group. At 6 h, expression of HSD11B1, TNF and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. IL6 expression increased significantly more in response to insulin in the insulin-resistant than in the insulin-sensitive group. CD68 was overexpressed in the insulin-resistant as compared with the insulin-sensitive group at both 0 and 6 h.


CONCLUSIONS
These data suggest that genes adversely affecting insulin sensitivity hyperrespond to insulin, while genes enhancing insulin sensitivity hyporespond to insulin in insulin-resistant human adipose tissue in vivo.
Westerbacka
J
J
Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 340, FIN-00029 HUCH, Helsinki, Finland. jukka.westerbacka@helsinki.fi
Cornér
A
A
Kannisto
K
K
Kolak
M
M
Makkonen
J
J
Korsheninnikova
E
E
Nyman
T
T
Hamsten
A
A
Fisher
R M
RM
Yki-Järvinen
H
H
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008875:Middle Aged; D012016:Reference Values
D007328:Insulin