title: Insulin granules. Insulin secretory granules control autophagy in pancreatic β cells.
abstract: Pancreatic β cells lower insulin release in response to nutrient depletion. The question of whether starved β cells induce macroautophagy, a predominant mechanism maintaining energy homeostasis, remains poorly explored. We found that, in contrast to many mammalian cells, macroautophagy in pancreatic β cells was suppressed upon starvation. Instead, starved β cells induced lysosomal degradation of nascent secretory insulin granules, which was controlled by protein kinase D (PKD), a key player in secretory granule biogenesis. Starvation-induced nascent granule degradation triggered lysosomal recruitment and activation of mechanistic target of rapamycin that suppressed macroautophagy. Switching from macroautophagy to insulin granule degradation was important to keep insulin secretion low upon fasting. Thus, β cells use a PKD-dependent mechanism to adapt to nutrient availability and couple autophagy flux to secretory function.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Goginashvili
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Erbs
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Spiegelhalter
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Kessler
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Mihlan
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Pasquier
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Krupina
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schieber
authors.affiliation: Dulbecco Telethon Institute and Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cinque
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Morvan
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Izabela
authors.initials: I
authors.lastname: Sumara
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schwab
authors.affiliation: Dulbecco Telethon Institute and Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy. Medical Genetics, Department of Medical and Translational Science Unit, Federico II University, Via Pansini 5, 80131 Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Settembre
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France. Nouvel Hôpital Civil, Laboratoire de Biochimie et de Biologie Moléculaire, Université de Strasbourg, 67091 Strasbourg, France. romeo.ricci@igbmc.fr.
authors.forename: Romeo
authors.initials: R
authors.lastname: Ricci
mesh_terms: D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D005215:Fasting; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D048292:Mitogen-Activated Protein Kinase 13 / Q000235:genetics; D011493:Protein Kinase C / Q000502:physiology; D022142:Secretory Vesicles / Q000378:metabolism / Q000502:physiology*
chemical_list: D007328:Insulin; D048292:Mitogen-Activated Protein Kinase 13; C089212:protein kinase D; D011493:Protein Kinase C