Mechanisms of Pancreatic -Cell Death in Type 1 and Type 2 Diabetes

Both types of diabetes are characterized by progressive -cell failure. 

It has been suggested that the mechanisms leading to nutrient- and cytokine-induced -cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1, nuclear factor (NF)-B, and Fas.  This research article reviews the mechanisms by which -cell death occurs, and if the mechanisms are the same.  

In vitro experiments were conducted using rat and human islet cells.  The results indicated that in type 1diabetes, invading immune cells produced cytokines, such as IL-1, tumor necrosis factor (TNF)-, and interferon (IFN)-. IL-1 and/or TNF- plus IFN- induced -cell apoptosis via the activation of -cell gene networks under the control of the transcription factors NF-B and STAT-1. NF-B activation led to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium.

Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) cause -cell dysfunction and may induce -cell apoptosis in type 2 diabetes.  High glucose, however, did not induce or activate IL-1, NF-B, or inducible nitric oxide synthase in rat or human -cells in vitro.  FFAs may cause -cell apoptosis via ER stress, that is NF-B and NO independent.

 Thus, cytokines and nutrients trigger -cell death by fundamentally different mechanisms, namely an NF-B– dependent mechanism that ends in caspase-3 activation for cytokines and an NF-B–independent mechanism for nutrients.

It can be concluded that the mechanisms of -cell death in type 1 and type 2 diabetes are different and hence independent approaches will be required to prevent -cell death in each case.

Reference: 

Cnop, Miriam, Nils Welsh, Jean-Christophe Jonas, Anne Jo ̈rns, Sigurd Lenzen, and Decio Eizirik. "Mechanisms of Pancreatic β-Cell Death in Type 1 and Type 2 Diabetes Many Differences, Few Similarities." Diabetes 54. Supplement 2 (2005): S97-S107.