title: Munc18c: a controversial regulator of peripheral insulin action.
abstract: Insulin resistance, a hallmark of impaired glucose tolerance and type 2 diabetes (T2D), arises from dysfunction of insulin action and subsequent glucose uptake by peripheral tissues, predominantly skeletal muscle and fat. Exocytosis of glucose transporter (GLUT4)-containing vesicles facilitated by soluble NSF (N-ethylmaleimide-sensitive factor) attachment receptor (SNARE) protein isoforms, and Munc18c (mammalian homolog of Unc-18c) mediates this glucose uptake. Emerging evidences, including recent human clinical studies, point to pivotal roles for Munc18c in peripheral insulin action in adipose and skeletal muscle. Intriguing new advances are also initiating debates regarding the molecular mechanism(s) controlling Munc18c action. The objective of this review is therefore to present a balanced perspective of new continuities and controversies surrounding the regulation and requirement for Munc18c in the regulation of peripheral insulin action.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Latha
authors.initials: L
authors.lastname: Ramalingam
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Yoder
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Eunjin
authors.initials: E
authors.lastname: Oh
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: dthurmon@iu.edu.
authors.forename: Debbie C
authors.initials: DC
authors.lastname: Thurmond
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics; D046912:Multiprotein Complexes / Q000378:metabolism; D051938:Munc18 Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism
chemical_list: D007328:Insulin; D046912:Multiprotein Complexes; D051938:Munc18 Proteins; D050600:SNARE Proteins; D005947:Glucose
keywords: GLUT4 vesicle exocytosis; SNARE proteins; adipose; glucose uptake; skeletal muscle