The Beta Cell in Type 2 Diabetes

被引:100
作者
Christensen, Ashley A. [1 ]
Gannon, Maureen [1 ,2 ,3 ,4 ]
机构
[1] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Med, 2213 Garland Ave,MRB 4 7465, Nashville, TN 37232 USA
[3] Tennessee Valley Hlth Author, Dept Vet Affairs, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA
关键词
beta-cell dysfunction; Dedifferentiation; Disallowed genes; ER stress; Oxidative stress; beta-cell metabolism; UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM; ALPHA-CELL; ER STRESS; MITOCHONDRIAL DYNAMICS; TRANSCRIPTION FACTORS; INSULIN-SECRETION; GLUCOSE; EXPRESSION; DEDIFFERENTIATION;
D O I
10.1007/s11892-019-1196-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of Review This review summarizes the alterations in the beta-cell observed in type 2 diabetes (T2D), focusing on changes in beta-cell identity and mass and changes associated with metabolism and intracellular signaling. Recent Findings In the setting of T2D, beta-cells undergo changes in gene expression, reverting to a more immature state and in some cases transdifferentiating into other islet cell types. Alleviation of metabolic stress, ER stress, and maladaptive prostaglandin signaling could improve beta-cell function and survival. The beta-cell defects leading to T2D likely differ in different individuals and include variations in beta-cell mass, development, beta-cell expansion, responses to ER and oxidative stress, insulin production and secretion, and intracellular signaling pathways. The recent recognition that some beta-cells undergo dedifferentiation without dying in T2D suggests strategies to revive these cells and rejuvenate their functionality.
引用
收藏
页数:8
相关论文
共 86 条
  • [1] Uncoupling protein-2 attenuates glucose-stimulated insulin, secretion in INS-1E insulinoma cells by lowering mitochondrial reactive oxygen species
    Affourtit, Charles
    Jastroch, Martin
    Brand, Martin D.
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2011, 50 (05) : 609 - 616
  • [2] Insufficient islet compensation to insulin resistance vs. reduced glucose effectiveness in glucose-intolerant mice
    Ahrén, B
    Pacini, G
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2002, 283 (04): : E738 - E744
  • [3] Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients
    Anello, M
    Lupi, R
    Spampinato, D
    Piro, S
    Masini, M
    Boggi, U
    Del Prato, S
    Rabuazzo, AM
    Purrello, F
    Marchetti, P
    [J]. DIABETOLOGIA, 2005, 48 (02) : 282 - 289
  • [4] Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes
    Arunagiri, Anoop
    Haataja, Leena
    Cunningham, Corey N.
    Shrestha, Neha
    Tsai, Billy
    Qi, Ling
    Liu, Ming
    Arvan, Peter
    [J]. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 2018, 1418 (01) : 5 - 19
  • [5] Endoplasmic Reticulum Stress and Type 2 Diabetes
    Back, Sung Hoon
    Kaufman, Randal J.
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, VOL 81, 2012, 81 : 767 - 793
  • [6] BECKER TC, 1994, J BIOL CHEM, V269, P21234
  • [7] The molecular mechanisms of pancreatic β-cell glucotoxicity: Recent findings and future research directions
    Bensellam, Mohammed
    Laybutt, D. Ross
    Jonas, Jean-Christophe
    [J]. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2012, 364 (1-2) : 1 - 27
  • [8] Pancreatic β-Cell Rest Replenishes Insulin Secretory Capacity and Attenuates Diabetes in an Extreme Model of Obese Type 2 Diabetes
    Boland, Brandon B.
    Brown, Charles, Jr.
    Boland, Michelle L.
    Cann, Jennifer
    Sulikowski, Michal
    Hansen, Gitte
    Gronlund, Rikke V.
    King, Wanda
    Rondinone, Cristina
    Trevaskis, James
    Rhodes, Christopher J.
    Grimsby, Joseph S.
    [J]. DIABETES, 2019, 68 (01) : 131 - 140
  • [9] β-Cell dysfunction in diabetes: a crisis of identity?
    Brereton, M. F.
    Rohm, M.
    Ashcroft, F. M.
    [J]. DIABETES OBESITY & METABOLISM, 2016, 18 : 102 - 109
  • [10] Beta-cell mitochondrial carriers and the diabetogenic stress response
    Brun, Thierry
    Maechler, Pierre
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2016, 1863 (10): : 2540 - 2549