title: Exocytosis proteins as novel targets for diabetes prevention and/or remediation?
abstract: 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 (solubleN-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.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: Arianne
authors.initials: A
authors.lastname: Aslamy
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and dthurmond@coh.org.|Department of Molecular and Cellular Endocrinology, Beckman Research Institute of City of Hope, Duarte, California.
authors.forename: Debbie C
authors.initials: DC
authors.lastname: Thurmond
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D016503:Drug Delivery Systems / Q000379:methods; D019317:Evidence-Based Medicine; D005089:Exocytosis / Q000187:drug effects*; D006801:Humans; D050576:Membrane Fusion Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D050576:Membrane Fusion Proteins; D033921:Vesicular Transport Proteins
keywords: SNARE proteins; diabetes; double C2-domain protein B; glucose homeostasis; glucose-stimulated insulin secretion; insulin resistance; syntaxin 4