title: Spatial and temporal coordination of insulin granule exocytosis in intact human pancreatic islets.
abstract: OBJECTIVE
  Insulin secretion is widely studied because it plays a central role in glucose homeostasis and diabetes. Processes from insulin granule fusion in beta cells to in vivo insulin secretion have been elucidated, but data at the cellular level do not fully account for several aspects of the macroscopic secretory pattern. Here we investigated how individual secretory events are coordinated spatially and temporally within intact human islets.
  
  
  METHODS
  We used the fluorescent probe neuropeptide Y (NPY)-pHluorin to visualise insulin granule secretion in isolated intact human islets.
  
  
  RESULTS
  We found that individual beta cells respond to increases in glucose concentration by releasing insulin granules in very discrete bursts with periods consistent with in vivo pulsatile insulin secretion. In successive secretory bursts during prolonged exposure to high glucose levels, secretory events progressively localised to preferential release sites, coinciding with the transition to second phase insulin secretion. Granule secretion was very synchronised in neighbouring beta cells, forming discrete regional clusters of activity.
  
  
  CONCLUSIONS
  These results reveal how individual secretory events are coordinated to produce pulsatile insulin secretion from human islets.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, 1580 NW 10th Ave, Miami, FL, 33136, USA. jalmaca@med.miami.edu.|Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL, 33136, USA. jalmaca@med.miami.edu.|Center for Plant Aging Research, Institute for Basic Science and Department of New Biology, DGIST, Daegu, Republic of Korea. jalmaca@med.miami.edu.
authors.forename: Joana
authors.initials: J
authors.lastname: Almaça
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Gaisano
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science and Department of New Biology, DGIST, Daegu, Republic of Korea.
authors.forename: Hong Gil
authors.initials: HG
authors.lastname: Nam
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL, 33136, USA. Per-Olof.Berggren@ki.se.|Rolf Luft Research Center for Diabetes & Endocrinology, Karolinska Institutet, Stockholm, Sweden. Per-Olof.Berggren@ki.se.|Lee Kong Chien School of Medicine, Nanyang Technical University, Singapore, Singapore. Per-Olof.Berggren@ki.se.|Imperial College, London, UK. Per-Olof.Berggren@ki.se.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, 1580 NW 10th Ave, Miami, FL, 33136, USA. acaicedo@med.miami.edu.|Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL, USA. acaicedo@med.miami.edu.|Program in Neuroscience, Miller School of Medicine, University of Miami, Miami, FL, USA. acaicedo@med.miami.edu.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Caicedo
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000378:metabolism
chemical_list: D007328:Insulin; D009478:Neuropeptide Y; D049452:Green Fluorescent Proteins; D005947:Glucose
keywords: Exocytosis; Human islets; Insulin granule; Pulsatile secretion