title: Pancreatic β-Cell Adaptive Plasticity in Obesity Increases Insulin Production but Adversely Affects Secretory Function.
abstract: Pancreatic β-cells normally produce adequate insulin to control glucose homeostasis, but in obesity-related diabetes, there is a presumed deficit in insulin production and secretory capacity. In this study, insulin production was assessed directly in obese diabetic mouse models, and proinsulin biosynthesis was found to be contrastingly increased, coupled with a significant expansion of the rough endoplasmic reticulum (without endoplasmic reticulum stress) and Golgi apparatus, increased vesicular trafficking, and a depletion of mature β-granules. As such, β-cells have a remarkable capacity to produce substantial quantities of insulin in obesity, which are then made available for immediate secretion to meet increased metabolic demand, but this comes at the price of insulin secretory dysfunction. Notwithstanding, it can be restored. Upon exposing isolated pancreatic islets of obese mice to normal glucose concentrations, β-cells revert back to their typical morphology with restoration of regulated insulin secretion. These data demonstrate an unrealized dynamic adaptive plasticity of pancreatic β-cells and underscore the rationale for transient β-cell rest as a treatment strategy for obesity-linked diabetes.
authors: Kovler Diabetes Center, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL.
authors: Cristina
authors: C
authors: Alarcon
authors: Kovler Diabetes Center, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL.
authors: Brandon B
authors: BB
authors: Boland
authors: Kovler Diabetes Center, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL.
authors: Yuji
authors: Y
authors: Uchizono
authors: Kovler Diabetes Center, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL.
authors: Patrick C
authors: PC
authors: Moore
authors: Kovler Diabetes Center, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL.
authors: Bryan
authors: B
authors: Peterson
authors: Kovler Diabetes Center, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL.
authors: Suryalekha
authors: S
authors: Rajan
authors: Kovler Diabetes Center, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL.
authors: Olivia S
authors: OS
authors: Rhodes
authors: Institute for Molecular Bioscience, Queensland Bioscience Precinct, The University of Queensland, Brisbane, Queensland, Australia.
authors: Andrew B
authors: AB
authors: Noske
authors: Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, MI.
authors: Leena
authors: L
authors: Haataja
authors: Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, MI.
authors: Peter
authors: P
authors: Arvan
authors: Institute for Molecular Bioscience, Queensland Bioscience Precinct, The University of Queensland, Brisbane, Queensland, Australia.
authors: Bradly J
authors: BJ
authors: Marsh
authors: Advanced Electron Microscope Core Facility, The University of Chicago, Chicago, IL.
authors: Jotham
authors: J
authors: Austin
authors: Kovler Diabetes Center, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL cjrhodes@uchicago.edu.
authors: Christopher J
authors: CJ
authors: Rhodes
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000066670:Cell Plasticity; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000473:pathology; D006056:Golgi Apparatus / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000502:physiology*; D051379:Mice; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011384:Proinsulin / Q000096:biosynthesis* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D033921:Vesicular Transport Proteins; D011384:Proinsulin