Regulation of insulin action and insulin secretion by SNARE-mediated vesicle exocytosis

Debbie C. Thurmond

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Maintenance of glucose homeostasis requires 'cross-talk' between pancreatic insulin secretion and insulin signaling in the peripheral tissues. Both insulin secretion and glucose uptake are regulated exocytotic processes mediated by SNARE protein complexes. SNARE core complexes are heterotrimeric, composed of syntaxin, SNAP-25/23 and VAMP2 proteins in a 1:1:1 ratio. It has become clear that we must thoroughly define the precise mechanisms underlying insulin-stimulated GLUT4 vesicle translocation by skeletal muscle and adipose cells as well as glucose-stimulated insulin secretion by pancreatic beta cells in order to develop therapeutic strategies to better treat and eventually cure diabetic patients. In this chapter, I will examine the molecular interactions responsible for these SNARE dependent events. Similarities and differences in molecular machinery, exocytosis mechanisms as well as the impact of accessory proteins such as Munc18 and Rab GTPases will be discussed. New findings on alterations of particular SNARE proteins upon glucose homeostasis are described in terms of potential for pharmacological targets for intervention. In 1957 Lacy and colleagues published immunofluorescent and later electron microscopy images of islet beta cells filled with darkened organelles, or insulin granules. These granules were later shown to fuse with the plasma membrane to release insulin.1-3Analogously, in 1990 the localization of the insulin-responsive glucose transporter 'GLUT4' to intracellular vesicles of adipocytes was revealed, and these GLUT4-storage vesicles were later shown to fuse with the plasma membrane upon stimulation with insulin, to ultimately facilitate glucose disposal. 4,5 However, it was not until 1993 that the molecular basis for vesicle fusion and secretion, termed 'vesicle exocytosis', was elucidated by the discovery of SNARE proteins (soluble N-ethylmaleimide sensitive factor attachment protein receptor)6,7.

Original languageEnglish (US)
Title of host publicationMechanisms of Insulin Action
Subtitle of host publicationMedical Intelligence Unit
PublisherSpringer New York
Pages52-70
Number of pages19
ISBN (Print)9780387722030
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Medicine(all)

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    Thurmond, D. C. (2007). Regulation of insulin action and insulin secretion by SNARE-mediated vesicle exocytosis. In Mechanisms of Insulin Action: Medical Intelligence Unit (pp. 52-70). Springer New York. https://doi.org/10.1007/978-0-387-72204-7_3