Free Fatty Acids and Cytokines Induce Pancreatic ß-Cell Apoptosis by Different Mechanisms

Free Fatty Acids and Cytokines Induce Pancreatic ß-Cell Apoptosis by Different Mechanisms

(I've scrubbed the distracting reference numbers from some excerpts of the introduction and I'm also going to try to cite only the information pertinent to T2)

Hypercaloric diets containing large amounts of fat, also called the Western diet, contribute to a major extent to the increasing prevalence of obesity and type 2 diabetes mellitus (T2DM). T2DM is characterized by peripheral insulin resistance, pancreatic ß-cell dysfunction, and decreased ß-cell mass associated with increased rates of ß-cell apoptosis. Elevated levels of circulating free fatty acids (FFAs) contribute to the pathogenesis of T2DM. High concentrations of FFAs lead to both impairment of insulin action and ß-cell dysfunction.  Moreover, FFAs have been shown to cause ß -cell death, mainly by apoptosis. 

Of note, increased adiposity is associated not only with increased FFA release but also with adipocyte secretion of a variety of cytokines and cytokine-like adipokines, such as TNF -α, IL-6, leptin, resistin, and adiponectin. TNF-α has direct cytotoxic effects on pancreatic ß -cells, especially in combination with other cytokines.

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