Exocytosis proteins as novel targets for diabetes prevention and/or remediation?

Diabetes remains one of the leading causes of morbidity and mortality worldwide, affecting an estimated 422 million adults. In the US, it is predicted that one in every three children born as of 2000 will suffer from diabetes in their lifetime. Type 2 diabetes results from combinatorial defects in p...

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Bibliographic Details
Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2017-05, Vol.312 (5), p.R739-R752
Main Authors: Aslamy, Arianne, Thurmond, Debbie C
Format: Article
Language:English
Subjects:
Animals
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - prevention & control
Drug Delivery Systems - methods
Evidence-Based Medicine
Exocytosis - drug effects
Humans
Membrane Fusion Proteins - antagonists & inhibitors
Membrane Fusion Proteins - metabolism
Models, Biological
Molecular Targeted Therapy - methods
Review
Vesicular Transport Proteins - antagonists & inhibitors
Vesicular Transport Proteins - metabolism
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Summary:Diabetes remains one of the leading causes of morbidity and mortality worldwide, affecting an estimated 422 million adults. In the US, it is predicted that one in every three children born as of 2000 will suffer from diabetes in their lifetime. Type 2 diabetes results from combinatorial defects in pancreatic β-cell glucose-stimulated insulin secretion and in peripheral glucose uptake. Both processes, insulin secretion and glucose uptake, are mediated by exocytosis proteins, SNARE (soluble -ethylmaleimide-sensitive factor attachment protein receptor) complexes, Sec1/Munc18 (SM), and double C2-domain protein B (DOC2B). Increasing evidence links deficiencies in these exocytosis proteins to diabetes in rodents and humans. Given this, emerging studies aimed at restoring and/or enhancing cellular levels of certain exocytosis proteins point to promising outcomes in maintaining functional β-cell mass and enhancing insulin sensitivity. In doing so, new evidence also shows that enhancing exocytosis protein levels may promote health span and longevity and may also harbor anti-cancer and anti-Alzheimer's disease capabilities. Herein, we present a comprehensive review of the described capabilities of certain exocytosis proteins and how these might be targeted for improving metabolic dysregulation.
ISSN:0363-6119
1522-1490
DOI:10.1152/ajpregu.00002.2017