Pathophysiological mechanisms of insulin resistance

In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the pathophysiology of insulin resistance:
1. Direct and indirect impairment of insulin sensitivity by increased circulating free fatty acids (FFA).
2. Inflammation in adipose tissue with enhanced production of cytokines.
3. Mitochondrial dysfunction.
In addition we studied early alterations in β-cell function during initial weight gain.