Free Fatty Acid Induced Insulin Resistance (FFAIR)

• intramyocellular lipid metabolites [ Time Frame: after 4 hours lipid infusion ] [ Designated as safety issue: No ]
  Muscle biopsies are taken before, after 2.5 and 4 hours of lipid infusion
  
  

• insulin resistance of glucose uptake and mitochondrial function [ Time Frame: after 4 hours lipid infusion ] [ Designated as safety issue: No ]
  Mitochondrial function will bes assessed from muscle biopsy samples taken after 4 hours, insulin sensitivity will be assessed from hyperinsulinemic-euglycemic clamps following 4 hours lipid infusion
  
  

Increased availability of free fatty acids impairs glucose disposal in young healthy humans. Patients with type 2 diabetes have reduced whole body glucose disposal, increased ectopic lipid deposition in skeletal muscle and the liver and impaired mitochondrial function. Recent studies suggest that lipid metabolites such as diacylglycerol (DAG), ceramides and long-chain acyl-coA represent the active mediators inducing insulin resistance. Possible targets are DAG-sensitive Proteinkinase C (PKC θ, PKC ε) which inhibit the insulin signaling cascade and ceramides which interfere with the insulin signaling cascade at Proteinkinase B/AKT. Prior studies raised controvesial evidence, thus, it is yet unclear, whether DAG or ceramides are the primary agents inducig lipid-induced insulin resistance. Therefore, the current study aims to explore the time course of the appearance of intramyocellular lipid compunds during lipid infusion in parallel assessing markers of impaired insulin action.