Type 2 diabetes mellitus: not quite exciting enough?

被引:82
作者
Ashcroft, F
Rorsman, P
机构
[1] Univ Oxford, Physiol Lab, Oxford OX1 3PT, England
[2] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England
关键词
D O I
10.1093/hmg/ddh066
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Type 2 diabetes mellitus is a serious metabolic disease that afflicts around 5% of the population in Western societies and over 150 million people worldwide. It is characterized by elevation of the blood glucose concentration, usually presents in middle age, and is exacerbated by obesity. Both genetic and environmental factors contribute to the disease but in the vast majority of cases the aetiology is still not understood. Here we present a novel hypothesis for the aetiology of type 2 diabetes. We postulate that the electrical activity of the insulin-secreting beta-cells of the pancreas acts to integrate the genetic and environmental factors that predispose to disease risk. Our hypothesis is supported by a substantial amount of data gathered from a range of different disciplines and makes predictions that can be tested experimentally both in vitro and in man.
引用
收藏
页码:R21 / R31
页数:11
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共 128 条
  • [61] Mitochondrial functional state in clonal pancreatic β-cells exposed to free fatty acids
    Koshkin, V
    Wang, XL
    Scherer, PE
    Chan, CB
    Wheeler, MB
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (22) : 19709 - 19715
  • [62] Targeted overactivity of β cell KATP channels induces profound neonatal diabetes
    Koster, JC
    Marshall, BA
    Ensor, N
    Corbett, JA
    Nichols, CG
    [J]. CELL, 2000, 100 (06) : 645 - 654
  • [63] A functional polymorphism in the promotor of UCP2 enhances obesity risk but reduces type 2 diabetes risk in obese middle aged humans
    Krempler, F
    Esterbauer, H
    Weitgasser, R
    Ebenbichler, C
    Patsch, JR
    Miller, K
    Xie, MQ
    Linnemayr, V
    Oberkofler, H
    Patsch, W
    [J]. DIABETES, 2002, 51 (11) : 3331 - 3335
  • [64] Uncoupling protein 2: A possible link between fatty acid excess and impaired glucose-induced insulin secretion?
    Lameloise, N
    Muzzin, P
    Prentki, M
    Assimacopoulos-Jeannet, F
    [J]. DIABETES, 2001, 50 (04) : 803 - 809
  • [65] Activation of the ATP-sensitive K+ channel by long chain acyl-CoA - A role in modulation of pancreatic beta-cell glucose sensitivity
    Larsson, O
    Deeney, JT
    Branstrom, R
    Berggren, PO
    Corkey, BE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (18) : 10623 - 10626
  • [66] Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials
    Larsson-Nyrén, G
    Sehlin, J
    Rorsman, P
    Renström, E
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2001, 441 (05): : 587 - 595
  • [67] Perchlorate is hypoglycaemic by amplifying glucose-stimulated insulin secretion in mice
    LarssonNyren, G
    [J]. ACTA PHYSIOLOGICA SCANDINAVICA, 1996, 158 (01): : 71 - 76
  • [68] An E23K single nucleotide polymorphism in the islet ATP-sensitive potassium channel gene (Kir6.2) contributes as much to the risk of Type II diabetes in Caucasians as the PPARγ Pro12Ala variant
    Love-Gregory, L
    Wasson, J
    Lin, J
    Skolnick, G
    Suarez, B
    Permutt, MA
    [J]. DIABETOLOGIA, 2003, 46 (01) : 136 - 137
  • [69] Mitochondrial function in normal and diabetic β-cells
    Maechler, P
    Wollheim, CB
    [J]. NATURE, 2001, 414 (6865) : 807 - 812
  • [70] CORRELATIONS OF INVIVO BETA-CELL FUNCTION-TESTS WITH BETA-CELL MASS AND PANCREATIC INSULIN CONTENT IN STREPTOZOCIN-ADMINISTERED BABOONS
    MCCULLOCH, DK
    KOERKER, DJ
    KAHN, SE
    BONNERWEIR, S
    PALMER, JP
    [J]. DIABETES, 1991, 40 (06) : 673 - 679