Exocytosis mechanisms underlying insulin release and glucose uptake: Conserved roles for Munc18c and syntaxin 4

Jenna L. Jewell, Eunjin Oh, Debbie C. Thurmond

Research output: Contribution to journalReview articlepeer-review

91 Scopus citations


Type 2 diabetes has been coined "a two-hit disease," as it involves specific defects of glucose-stimulated insulin secretion from the pancreatic beta cells in addition to defects in peripheral tissue insulin action required for glucose uptake. Both of these processes, insulin secretion and glucose uptake, are mediated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein core complexes composed of syntaxin, SNAP-23/25, and VAMP proteins. The SNARE core complex is regulated by the Sec1/Munc18 (SM) family of proteins, which selectively bind to their cognate syntaxin isoforms with high affinity. The process of insulin secretion uses multiple Munc18-syntaxin isoform pairs, whereas insulin action in the peripheral tissues appears to use only the Munc18c-syntaxin 4 pair. Importantly, recent reports have linked obesity and Type 2 diabetes in humans with changes in protein levels and single nucleotide polymorphisms (SNPs) of Munc18 and syntaxin isoforms relevant to these exocytotic processes, although the molecular mechanisms underlying the observed phenotypes remain incomplete (5, 104, 144). Given the conservation of these proteins in two seemingly disparate processes and the need to design and implement novel and more effective clinical interventions, it will be vitally important to delineate the mechanisms governing these conserved SNARE-mediated exocytosis events. Thus, we provide here an up-to-date historical review of advancements in defining the roles and molecular mechanisms of Munc18-syntaxin complexes in the pathophysiology of Type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)R517-R531
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3
StatePublished - Mar 2010


  • Diabetes
  • Glucose homeostasis
  • Glucosestimulated insulin secretion
  • Insulin resistance
  • Sec1/Munc18 proteins
  • Soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


Dive into the research topics of 'Exocytosis mechanisms underlying insulin release and glucose uptake: Conserved roles for Munc18c and syntaxin 4'. Together they form a unique fingerprint.

Cite this