**4. Insulin-resistance**

Several studies have demonstrated a potential association between PsO and increased serum fasting glucose levels, hyperinsulinemia, insulin-resistance, and type 2 diabetes. However, insulin resistance does not significantly correlate with PsO disease severity and duration (Gottlieb A et al, 2008).

Insulin resistance is a characteristic feature of most patients with Type 2 diabetes mellitus and is one of the MetS clinical features. Insulin is a pleiotropic hormone stimulating nutrient transport into cells, regulating gene expression, modifying enzymatic activity and regulating energy homeostasis (De Luca C et al, 2008).

Insulin exerted to these multiple functions through several intracellular signaling cascades, such as the phosphatidylinositol 3-kinase (PI3K)-AKT (also called protein kinase B (PKB)) pathway and the Ras-mitogen activated protein kinase (MAPK) pathway. PI3K-AKT is largely responsible for insulin action on glucose uptake and in the suppression of gluconeogenesis, while MAPK mediates gene expression and controls cell growth and differentiation, interacting with the first pathway. The insulin action is evidenced on target tissue, such as liver, adipose tissue and skeletal muscle (De Luca C et al, 2008).

In the liver, insulin regulates glucose metabolism depending on the meal or starvation, while in adipose tissue insulin signaling results in decreased hormone sensitive lipase activity and this anti-lipolytic effect inhibits free fatty acid efflux out of adipocytes (De Luca C et al, 2008).

Increased levels of TNF-alpha, IL-6 and FFAs produced by excess visceral adipose tissue can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction and they can determine the production of other inflammatory-related factors, such as CRP (Gottlieb A et al, 2008).

TNF-alpha causes a decrease in the autophosphorylation of tyrosine residues of insulin receptor (IR) and phosphorylation of insulin receptor substrate 1 (IRS-1) (Hotamisligil GS, 2003).

Thus, in psoriasis obesity and insulin resistance have a proinflammatory effect perpetuated through a positive feedback loop in PsO patients.
