Insulin action on expression of novel adipose genes in healthy and type 2 diabetic subjects.
OBJECTIVE
Adipose tissue secretes several molecules that may participate in metabolic cross-talk to other insulin-sensitive tissues. Thus, adipose tissue is a key endocrine organ that regulates insulin sensitivity in other peripheral insulin target tissues. We have studied the expression and acute insulin regulation of novel genes expressed in adipose tissue that are implicated in the control of whole body insulin sensitivity.


METHODS
Expression of adiponectin, c-Cbl-associated protein (CAP), 11-beta hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), and sterol regulatory element binding protein (SREBP)-1c was determined in subcutaneous adipose tissue from type 2 diabetic and age- and BMI-matched healthy men by real-time polymerase chain reaction analysis.


RESULTS
Expression of adiponectin, CAP, 11beta-HSD-1, and SREBP-1c was similar between healthy and type 2 diabetic subjects. Insulin infusion for 3 hours did not affect expression of CAP, 11beta-HSD-1, or adiponectin mRNA in either group. However, insulin infusion increased SREBP-1c expression by 80% in healthy, but not in type 2 diabetic, subjects.


CONCLUSIONS
Our results provide evidence that insulin action on SREBP-1c is dysregulated in adipose tissue from type 2 diabetic subjects. Impaired insulin regulation on gene expression of select targets in adipose tissue may contribute to the pathogenesis of type 2 diabetes.
Koistinen
Heikki A
HA
Department of Surgical Sciences, Karolinska Institute, Stockholm, Sweden. heikki.koistinen@hus.fi
Forsgren
Margareta
M
Wallberg-Henriksson
Harriet
H
Zierath
Juleen R
JR
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D052242:Adiponectin; D000273:Adipose Tissue / Q000737:chemistry*; D015992:Body Mass Index; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008875:Middle Aged; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050721:Proto-Oncogene Proteins c-cbl; D012333:RNA, Messenger / Q000032:analysis; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases
D052242:Adiponectin; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human