Study of Gene Activity in Fat and Muscle in Diabetics and Healthy Controls

Study of Gene Expression in Fat and Muscle Tissue in Type 2 Diabetics and Healthy Controls During Experimental Endotoxemia

The aim of the present protocol is to study gene activity in fat and muscle tissue in type 2 diabetics and healthy volunteers after injection of E. coli endotoxin.We hereby hope to gain insight in some mechanisms behind the association between inflammation and insulin resistance.

Numerous studies have shown an association between low-grade inflammation and insulin-resistance in type 2 diabetics. It is also well-known that septic patients often develop insulin-resistance. The pathogenetic mechanisms behind the association between inflammation and insulin-resistance is not fully understood. In this study we create an experimental inflammation by giving E. coli endotoxin 0,3 ng/kg iv to type 2 diabetics and healthy controls. Muscle biopsies are taken at 0, 2, 4 and 6 hours after injection, while fat biopsies are taken 0, 2, 4, 6 and 8 hours after endotoxin. mRNA for adiponectin, leptin, PPAR-gamma, PGC-1, PAI-1 and cytokines in tissue is later measured by RT-PCR. Blood samples are drawn on an hourly basis until 8 hours after endotoxin injection for common biochemical analyses including white blood cell count. Plasma is spared and later analyzed for cytokines, PAI-1 and VCAM-1/ICAM-1.

Low-grade inflammation, insulin resistance, Metabolism, Type 2 diabetes, Endotoxemia, Fat tissue, Muscle tissue, RT-PCR

Gene expression evaluated by measuring mRNA via RT-PCR. Plasma cytokine content, PLasma PAI-1 content, endotoxemia score

Inclusion Criteria: Healthy Type 2 diabetes Exclusion Criteria: Heart failure Lung disease Anti-coagulation treatment

Andreasen AS, Kelly M, Berg RM, Moller K, Pedersen BK. Type 2 diabetes is associated with altered NF-kappaB DNA binding activity, JNK phosphorylation, and AMPK phosphorylation in skeletal muscle after LPS. PLoS One. 2011;6(9):e23999. doi: 10.1371/journal.pone.0023999. Epub 2011 Sep 13.