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J Diabetes Res. 2018 Feb 19;2018:9601801. doi: 10.1155/2018/9601801. eCollection 2018.

Pancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes Therapy.

Author information

1
Pulmonary and Critical Care Medicine Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
Endocrine and Metabolic Research Center, University of Zulia, Maracaibo, Venezuela.
3
Grupo de Investigación Altos Estudios de Frontera (ALEF), Universidad Simón Bolívar, Cúcuta, Colombia.
4
Clinical Pharmacology Unit. School of Medicine José María Vargas, Central University of Venezuela, Caracas, Venezuela.

Abstract

Purpose of Review:

Describing the diverse molecular mechanisms (particularly immunological) involved in the death of the pancreatic beta cell in type 1 and type 2 diabetes mellitus.

Recent Findings:

Beta cell death is the final event in a series of mechanisms that, up to date, have not been entirely clarified; it represents the pathophysiological mechanism in the natural history of diabetes mellitus. These mechanisms are not limited to an apoptotic process only, which is characteristic of the immune-mediated insulitis in type 1 diabetes mellitus. They also include the action of proinflammatory cytokines, the production of reactive oxygen species, DNA fragmentation (typical of necroptosis in type 1 diabetic patients), excessive production of islet amyloid polypeptide with the consequent endoplasmic reticulum stress, disruption in autophagy mechanisms, and protein complex formation, such as the inflammasome, capable of increasing oxidative stress produced by mitochondrial damage.

Summary:

Necroptosis, autophagy, and pyroptosis are molecular mechanisms that modulate the survival of the pancreatic beta cell, demonstrating the importance of the immune system in glucolipotoxicity processes and the potential role for immunometabolism as another component of what once known as the "ominous octet."

PMID:
29670917
PMCID:
PMC5836465
DOI:
10.1155/2018/9601801
[Indexed for MEDLINE]
Free PMC Article

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