AMP-activated protein kinase activators in diabetic ulcers: from animal studies to Phase II drugs under investigation

被引:24
作者
Lin, Jiun-Tsai [1 ]
Chen, Han-Min [2 ,3 ]
Chiu, Chih-Hsien [4 ]
Liang, Yao-Jen [2 ,3 ,5 ]
机构
[1] Energenesis Biomed Co Ltd, New Taipei City, Taiwan
[2] Fu Jen Catholic Univ, Grad Inst Appl Sci & Engn, New Taipei City 24205, Taiwan
[3] Fu Jen Catholic Univ, Dept & Inst Life Sci, New Taipei City 24205, Taiwan
[4] Natl Taiwan Univ, Dept Anim Sci & Technol, Taipei 10764, Taiwan
[5] Fu Jen Catholic Univ, Biomed & Photon Interdisciplinary Res Ctr, New Taipei City 24205, Taiwan
关键词
AMP-activated protein kinase; diabetes mellitus; diabetic ulcer; metformin; wound healing; GLYCATION END-PRODUCTS; HEPATIC GLUCOSE-PRODUCTION; ALPHA-LIPOIC ACID; ELEMENT-BINDING PROTEIN; SKELETAL-MUSCLE; EPIGALLOCATECHIN GALLATE; TRANSCRIPTION FACTOR; GLUT4; TRANSLOCATION; LIPID-METABOLISM; GENE-EXPRESSION;
D O I
10.1517/13543784.2014.922951
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Diagnosed cases of diabetes have gradually increased year by year, and research on diabetes mellitus (DM) has attracted greater attention fromthe medical profession. Diabetic ulcers present persistent pain and the risk of bacterial infection. However, no promising treatment methods have been found. As a regulator of cellular energy balance, 5' adenosine monophosphate-activated protein kinase (AMPK) has been suggested as a drug target for DM, including such drugs as metformin. Areas covered: This review summarizes the current research and clinical trials of AMPK activators on diabetic wound healing and diabetic ulcers. Furthermore, it discusses the feasibility of AMPK activators in the treatment of diabetic wounds. Expert opinion: Animal studies have demonstrated that AMPK activators are a potential treatment for diabetic ulcers. AMPK activators alleviate tissue inflammation and promote re-epithelialization in diabetic wounds. However, due to the complicated pathological mechanism of diabetic foot ulcers, AMPK activators should be combined with other approaches. The new strategies for combination therapy with AMPK activator may provide a therapeutic advantage for patients with diabetic ulcers.
引用
收藏
页码:1253 / 1265
页数:13
相关论文
共 76 条
  • [1] The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways
    Ahn, Jiyun
    Lee, Hyunjung
    Kim, Suna
    Park, Jaeho
    Ha, Taleyoul
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 373 (04) : 545 - 549
  • [2] Liver adenosine monophosphate-activated kinase-α2 catalytic subunit is a key target for the control of hepatic glucose production by adiponectin and leptin but not insulin
    Andreelli, F
    Foretz, M
    Knauf, C
    Cani, PD
    Perrin, C
    Iglesias, MA
    Pillot, B
    Bado, A
    Tronche, F
    Mithieux, G
    Vaulont, S
    Burcelin, R
    Viollet, B
    [J]. ENDOCRINOLOGY, 2006, 147 (05) : 2432 - 2441
  • [3] MODULATION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE-ACTIVITY WITH CAMP AND WITH PROTEIN FRACTIONS OF RAT-LIVER CYTOSOL
    BEG, ZH
    ALLMANN, DW
    GIBSON, DM
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1973, 54 (04) : 1362 - 1369
  • [4] Effect of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats
    Bergeron, R
    Previs, SF
    Cline, GW
    Perret, P
    Russell, RR
    Young, LH
    Shulman, GI
    [J]. DIABETES, 2001, 50 (05) : 1076 - 1082
  • [5] Cellular and molecular basis of wound healing in diabetes
    Brem, Harold
    Tomic-Canic, Marjana
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (05) : 1219 - 1222
  • [6] A COMMON BICYCLIC PROTEIN-KINASE CASCADE INACTIVATES THE REGULATORY ENZYMES OF FATTY-ACID AND CHOLESTEROL-BIOSYNTHESIS
    CARLING, D
    ZAMMIT, VA
    HARDIE, DG
    [J]. FEBS LETTERS, 1987, 223 (02) : 217 - 222
  • [7] CARLSON CA, 1973, J BIOL CHEM, V248, P378
  • [8] Inhibition of GLUT4 translocation by Tbc1d1, a Rab GTPase-activating protein abundant in skeletal muscle, is partially relieved by AMP-activated protein kinase activation
    Chavez, Jose A.
    Roach, William G.
    Keller, Susanna R.
    Lane, William S.
    Lienhard, Gustav E.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (14) : 9187 - 9195
  • [9] Topical treatment with anti-oxidants and Au nanoparticles promote healing of diabetic wound through receptor for advance glycation end-products
    Chen, Siang-An
    Chen, Han-Min
    Yao, Yeong-Der
    Hung, Chi-Feng
    Tu, Chi-Shun
    Liang, Yao-Jen
    [J]. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2012, 47 (05) : 875 - 883
  • [10] Potential AMPK activators of cucurbitane triterpenoids from Siraitia grosvenorii Swingle
    Chen, Xu-bing
    Zhuang, Jing-jing
    Liu, Jun-hua
    Lei, Min
    Ma, Lei
    Chen, Jing
    Shen, Xu
    Hu, Li-hong
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (19) : 5776 - 5781