GROUP NAME: OBESITY, INFLAMATION AND INSULIN RESISTANCE
Insulin resistance (a smaller than normal response to a given amount of
insulin) is an important contributor to the pathogenesis of type 2
diabetes (T2D), and Obesity a risk factor for developing this disease.
The obese state is characterized by what has been called low-grade
systemic inflammation. Adipose tissue produces and releases a variety
of proinflamatory and anti-inflamatory factors, including the
adipokines leptin, adiponectin, resistin and visfating, as well as
cytokines and chemokines, such as TNF-alpha, IL-6, IL-1 beta, CRP.
Direct exposure of peripheral tissues to these cytokines through
activation of stress kinases and proinflammatory factors, inhibits
insulin signalling and induces a state of insulin resistance in several
systems including muscle cells and adipocytes, by affecting insulin
receptor substrate (IRS) proteins. Regulation involves
proteasome-mediated degradation, phosphatase-mediated dephosphorylation
and a mechanism involving Ser phosphorylation of IRS-1 that converts
IRS-1 in an inhibitor of the insulin receptor Tyr kinase activity.
Rosiglitazone is an insulin-sensitizing drug from the family of the
thiazolidinediones that has recently been introduced as therapeutic
agent for the treatment of T2D.
mechanisms by which this compound restored insulin
sensitivity are not completely understood. Moreover, whether
other nuclear receptor agonists could improve insulin action remains to
be fully explored. The cellular and animal models that we have
developed in our group could be excellent tools for investigating the
molecular basis of insulin resistance and the therapeutic potential of