Targeting hepatic glucose metabolism in the treatment of type 2 diabetes

被引:278
作者
Rines, Amy K.
Sharabi, Kfir
Tavares, Clint D. J.
Puigserver, Pere [1 ]
机构
[1] Harvard Med Sch, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
GLYCOGEN-SYNTHASE KINASE-3; GLUCAGON RECEPTOR ANTAGONIST; SMALL-MOLECULE INHIBITORS; PHOSPHATASE 1B PTP1B; LOWERS BLOOD-GLUCOSE; PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; HEPATOSELECTIVE GLUCOKINASE ACTIVATOR; INSULIN-RESISTANCE; PHOSPHORYLASE INHIBITOR; GLYCEMIC CONTROL;
D O I
10.1038/nrd.2016.151
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Type 2 diabetes mellitus is characterized by the dysregulation of glucose homeostasis, resulting in hyperglycaemia. Although current diabetes treatments have exhibited some success in lowering blood glucose levels, their effect is not always sustained and their use may be associated with undesirable side effects, such as hypoglycaemia. Novel antidiabetic drugs, which may be used in combination with existing therapies, are therefore needed. The potential of specifically targeting the liver to normalize blood glucose levels has not been fully exploited. Here, we review the molecular mechanisms controlling hepatic gluconeogenesis and glycogen storage, and assess the prospect of therapeutically targeting associated pathways to treat type 2 diabetes.
引用
收藏
页码:786 / 804
页数:19
相关论文
共 252 条
  • [1] Contributions of β-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose
    Abdul-Ghani, MA
    Tripathy, D
    DeFronzo, RA
    [J]. DIABETES CARE, 2006, 29 (05) : 1130 - 1139
  • [2] A link between hepatic glucose production and peripheral energy metabolism via hepatokines
    Abdul-Wahed, Aya
    Gautier-Stein, Amandine
    Casteras, Sylvie
    Soty, Maud
    Roussel, Damien
    Romestaing, Caroline
    Guillou, Herve
    Tourette, Jean-Andre
    Pleche, Nicolas
    Zitoun, Carine
    Gri, Blandine
    Sardella, Anne
    Rajas, Fabienne
    Mithieux, Gilles
    [J]. MOLECULAR METABOLISM, 2014, 3 (05): : 531 - 543
  • [4] Metformin: an old but still the best treatment for type 2 diabetes
    Aguayo Rojas, Lilian Beatriz
    Gomes, Marilia Brito
    [J]. DIABETOLOGY & METABOLIC SYNDROME, 2013, 5
  • [5] Aicher Thomas D, 2010, Expert Rev Clin Pharmacol, V3, P209, DOI 10.1586/ecp.10.1
  • [6] [Anonymous], 2014, NAT DIAB STAT REP ES
  • [7] [Anonymous], DRUGS S1
  • [8] Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1α and oxidative phosphorylation
    Arany, Zoltan
    Wagner, Bridget K.
    Ma, Yanhong
    Chinsomboon, Jessica
    Laznik, Dina
    Spiegelman, Bruce M.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (12) : 4721 - 4726
  • [9] The transcription factor CCAAT/enhancer-binding protein β regulates gluconeogenesis and phosphoenolpyruvate carboxykinase (GTP) gene transcription during diabetes
    Arizmendi, C
    Liu, S
    Croniger, C
    Poli, V
    Friedman, JE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (19) : 13033 - 13040
  • [10] In vitro and in vivo suppression of gluconeogenesis by inhibition of pyruvate carboxylase
    Bahl, JJ
    Matsuda, M
    DeFronzo, RA
    Bressler, R
    [J]. BIOCHEMICAL PHARMACOLOGY, 1997, 53 (01) : 67 - 74