Molecular and cellular mechanisms linking inflammation to insulin resistance and b-cell dysfunction
نویسنده :
تاریخ انتشار : 1396/07/02
Obesity is a major public health problem worldwide, and it is associated with an
increased risk of developing type 2 diabetes. It is now commonly accepted that
chronic inflammation associated with obesity induces insulin resistance and b-cell
dysfunction in diabetic patients. Obesity-associated inflammation is characterized
by increased abundance of macrophages and enhanced production of inflammatory
cytokines in adipose tissue. Adipose tissue macrophages are suggested to be
the major source of local and systemic inflammatory mediators such as tumor necrosis
factor a, interleukin (IL)-1b, and IL-6. These cytokines induce insulin resistance in
insulin target tissues by activating the suppressors of cytokine signaling proteins,
several kinases such as c-Jun N-terminal kinase, IkB kinase b, and protein kinase
C, inducible nitric oxide synthase, extracellular signal-regulated kinase, and protein
tyrosine phosphatases such as protein tyrosine phosphatase 1B. These activated
factors impair the insulin signaling at the insulin receptor and the insulin receptor substrates
levels. The same process most likely occurs in the pancreas as it contains a
pool of tissue-resident macrophages. High concentrations of glucose or palmitate
via the chemokine production promote further immune cell migration and infiltration
into the islets. These events ultimately induce inflammatory responses leading to the
apoptosis of the pancreatic b cells. In this review, the cellular and molecular players
that participate in the regulation of obesity-induced inflammation are discussed,
with particular attention being placed on the roles of the molecular players linking
inflammation to insulin resistance and b-cell dysfunction.