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

Expert Opinion on Investigational Drugs

Volumn 23, Issue 9, 2014, Pages 1253-1265

  Lin, Jiun Tsai ^a   Chen, Han Min ^b   Chiu, Chih Hsien ^c   Liang, Yao Jen ^b  

^a ENERGENESIS BIOMEDICAL CO LTD   (Taiwan)

^b FU JEN CATHOLIC UNIVERSITY   (Taiwan)

^c NATIONAL TAIWAN UNIVERSITY   (Taiwan)

Author keywords

AMP activated protein kinase; Diabetes mellitus; Diabetic ulcer; Metformin; Wound healing

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE ACTIVATOR; INSULIN; METFORMIN; ANTIDIABETIC AGENT;

DIABETIC FOOT; DIABETIC PATIENT; EPITHELIZATION; FEASIBILITY STUDY; HUMAN; INFLAMMATION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); REVIEW; UNSPECIFIED SIDE EFFECT; WOUND HEALING; ANIMAL; DRUG DESIGN; DRUG EFFECTS; ENZYMOLOGY; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOLOGY;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; CLINICAL TRIALS, PHASE II AS TOPIC; DIABETIC FOOT; DRUG DESIGN; HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; MOLECULAR TARGETED THERAPY; WOUND HEALING;

EID: 84906043314     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2014.922951     Document Type: Review

References (80)

1. Beg ZH, Allmann DW, Gibson DM. Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and wth protein fractions of rat liver cytosol. Biochem Biophys Res Commun 1973;54:1362-9
2. Carlson CA, Kim KH. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem 1973;248:378-80
3. Carling D, Zammit VA, Hardie DG. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett 1987;223:217-22
4. Sim AT, Hardie DG. The low activity of acetyl-CoA carboxylase in basal and glucagon-stimulated hepatocytes is due to phosphorylation by the AMP-Activated protein kinase and not cyclic AMPdependent protein kinase. FEBS Lett 1988;233:294-8
5. Oakhill JS, Steel R, Chen ZP, et al. AMPK is a direct adenylate charge-regulated protein kinase. Science 2011;332:1433-5
6. Hardie DG. AMP-Activated protein kinase: The guardian of cardiac energy status. J Clin Invest 2004;114:465-8
7. Hardie DG, Hawley SA, Scott JW. AMP-Activated protein kinase-development of the energy sensor concept. J Physiol 2006;574:7-15
8. Shaw RJ, Kosmatka M, Bardeesy N, et al. The tumor suppressor LKB1 kinase directly activates AMP-Activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA 2004;101:3329-35
9. Jensen TE, Rose AJ, Jorgensen SB, et al. Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. Am J Physiol Endocrinol Metab 2007;292:E1308-17
10. Steinberg GR, Kemp BE. AMPK in health and disease. Physiol Rev 2009;89:1025-78
11. Li Y, Xu S, Mihaylova MM, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in dietinduced insulin-resistant mice. Cell Metab 2011;13:376-88
12. Uyeda K, Repa JJ. Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis. Cell Metab 2006;4:107-10
13. Kawaguchi T, Osatomi K, Yamashita H, et al. Mechanism for fatty acid "sparing" effect on glucose-induced transcription: Regulation of carbohydrate-responsive element-binding protein by AMPactivated protein kinase. J Biol Chem 2002;277:3829-35
14. Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, et al. 5 AMP-Activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 1999;48:1667-71
15. Chavez JA, Roach WG, Keller SR, et al. Inhibition of GLUT4 translocation by Tbc1d1, a Rab GTPase-Activating protein abundant in skeletal muscle, is partially relieved by AMP-Activated protein kinase activation. J Biol Chem 2008;283:9187-95
16. Thong FS, Bilan PJ, Klip A. The Rab GTPase-Activating protein AS160 integrates Akt, protein kinase C, and AMP-Activated protein kinase signals regulating GLUT4 traffic. Diabetes 2007;56:414-23
17. Ojuka EO, Jones TE, Nolte LA, et al. Regulation of GLUT4 biogenesis in muscle: Evidence for involvement of AMPK and Ca(2+). Am J Physiol Endocrinol Metab 2002;282:E1008-13
18. Andreelli F, Foretz M, Knauf C, et al. Liver adenosine monophosphate-Activated kinase-Alpha2 catalytic subunit is a key target for the control of hepatic glucose production by adiponectin and leptin but not insulin. Endocrinology 2006;147:2432-41
19. Bergeron R, Previs SF, Cline GW, et al. Effect of 5-Aminoimidazole-4- carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 2001;50:1076-82
20. Johnson AB, Webster JM, Sum CF, et al. The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients. Metabolism 1993;42:1217-22
21. Natali A, Ferrannini E. Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: A systematic review. Diabetologia 2006;49:434-41
22. Koo SH, Flechner L, Qi L, et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 2005;437:1109-11
23. Inoue E, Yamauchi J. AMP-Activated protein kinase regulates PEPCK gene expression by direct phosphorylation of a novel zinc finger transcription factor. Biochem Biophys Res Commun 2006;351:793-9
24. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193-203
25. Singer AJ, Clark RAF. Cutaneous wound healing. N Engl J Med 1999;341:738-46
26. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest 2007;117:1219-22
27. Lamers ML, Almeida ME, Vicente-Manzanares M, et al. High glucose-mediated oxidative stress impairs cell migration. PLoS One 2011;6:e22865
28. Gurtner GC, Werner S, Barrandon Y, et al. Wound repair and regeneration. Nature 2008;453:314-21
29. Huijberts MS, Schaper NC, Schalkwijk CG. Advanced glycation end products and diabetic foot disease. Diabetes Metab Res Rev 2008;24(Suppl 1):S19-24
30. Lee SJ, Lee KW. Protective effect of (-)-epigallocatechin gallate against advanced glycation endproducts-induced injury in neuronal cells. Biol Pharm Bull 2007;30:1369-73
31. Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression. Horm Metab Res 2012;44:891-5
32. Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Metformin inhibits advanced glycation end products (AGEs)-induced growth and VEGF expression in MCF-7 breast cancer cells by suppressing AGEs receptor expression via AMP-Activated protein kinase. Horm Metab Res 2013;45:387-90
33. Sharman D. Moist wound healing: A review of evidence, application and outcome. Diabet Foot 2003;6:112-20
34. Marrotte EJ, Chen DD, Hakim JS, Chen AF. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice. J Clin Invest 2010;120:4207-19
35. Sosiak T, Evans W. Hyperbaric Medicine in Ontario: Clinical Overview, Resource Challenges. Ont Med Rev 2005;72:51-4
36. Li FY, Lam KS, Tse HF, et al. Endothelium-selective activation of AMP-Activated protein kinase prevents diabetes mellitus-induced impairment in vascular function and reendothelialization via induction of heme oxygenase-1 in mice. Circulation 2012;126:1267-77
37. Ni YX. Therapeutic effect of berberine on 60 patients with type II diabetes mellitus and experimental research. Zhong Xi Yi Jie He Za Zhi 1988;8:711-13.07
38. Srinivasan M. Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 1972;26:269-70
39. Nuraliev Iu N, Avezov GA. The efficacy of quercetin in alloxan diabetes. Eksp Klin Farmakol 1992;55:42-4
40. Yokozawa T, Oura H, Kawashima Y. Effect of serial administration of ginsenoside-Rb2 in diabetic rats: In terms of carbohydrate and lipid metabolites. Chem Pharm Bull (Tokyo) 1987;35:4872-7
41. Waltner-Law ME, Wang XL, Law BK, et al. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem 2002;277:34933-40
42. Lamers ML, Almeida ME, Vicente-Manzanares M, et al. High glucose-mediated oxidative stress impairs cell migration. PLoS One 2011;6:e22865
43. Goransson O, McBride A, Hawley SA, et al. Mechanism of action of A-769662, a valuable tool for activation of AMP-Activated protein kinase. J Biol Chem 2007;282:32549-60
44. Pang T, Zhang ZS, Gu M, et al. Small molecule antagonizes autoinhibition and activates AMP-Activated protein kinase in cells. J Biol Chem 2008;283:16051-60
45. Li YY, Yu LF, Zhang LN, et al. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice. Toxicol Appl Pharmacol 2013;273:325-34
46. Chen SA, Chen HM, Yao YD, et al Eur J Pharm Sci 2012;47:875-83
47. Leu JG, Chen SA, Chen HM, et al Nanomedicine 2012;8:767-75
48. Loughlin DT, Artlett CM. Precursor of advanced glycation end products mediates ER-stress-induced caspase-3 activation of human dermal fibroblasts through NAD(P)H oxidase 4. PLoS One 2010;5:e11093
49. Goova MT, Li J, Kislinger T, et al. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol 2001;159:513-25
50. Salminen A, Hyttinen JM, Kaarniranta K. AMP-Activated protein kinase inhibits NF-kappaB signaling and inflammation: Impact on healthspan and lifespan. J Mol Med 2011;89:667-76
51. Mechanisms of Improved Wound Healing and Protein Synthesis of Insulin and Metformin. Available from: Http://clinicaltrials.gov/show/NCT01666665 [Last accessed 12 December 2013]
52. Assessment of Mechanisms of Improved Wound Healing. Available from: Http://clinicaltrials.gov/show/NCT00673309 [Last accessed 4 May 2012]
53. DPP IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Type 2 Diabetes. Available from: Http://clinicaltrials.gov/show/NCT01472432 [Last accessed 4 December 2011]
54. Suzuki K, Uchida K, Nakanishi N, et al. Cilostazol activates AMP-Activated protein kinase and restores endothelial function in diabetes. Am J Hypertens 2008;21:451-7
55. Zhang L, He H, Balschi JA. Metformin and phenformin activate AMP-Activated protein kinase in the heart by increasing cytosolic AMP concentration. Am J Physiol Heart Circ Physiol 2007;293:H457-66
56. Rothbart SB, Racanelli AC, Moran RG. Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomas. Cancer Res 2010;70:10299-309
57. Coletta DK, Sriwijitkamol A, Wajcberg E, et al. Pioglitazone stimulates AMP-Activated protein kinase signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo: A randomised trial. Diabetologia 2009;52:723-32
58. Hwang JT, Park IJ, Shin JI, et al. Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-Activated protein kinase. Biochem Biophys Res Commun 2005;338:694-9
59. Kola B, Hubina E, Tucci SA, et al. Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-Activated protein kinase. J Biol Chem 2005;280:25196-201
60. Park KG, Min AK, Koh EH, et al. Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-Activated protein kinase (AMPK)-dependent and AMPKindependent pathways. Hepatology 2008;48:1477-86
61. Shen QW, Zhu MJ, Tong J, et al. Ca2+/calmodulin-dependent protein kinase kinase is involved in AMPactivated protein kinase activation by alpha-lipoic acid in C2C12 myotubes. Am J Physiol Cell Physiol 2007;293:C1395-403
62. Turner N, Li JY, Gosby A, et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-Activated protein kinase and improve insulin action. Diabetes 2008;57:1414-18
63. Kim T, Davis J, Zhang AJ, et al. Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells. Biochem Biophys Res Commun 2009;388:377-82
64. Lim HW, Lim HY, Wong KP. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action. Biochem Biophys Res Commun 2009;389:187-92
65. Ahn J, Lee H, Kim S, et al. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun 2008;373:545-9
66. Park MW, Ha J, Chung SH. 20 (S)-ginsenoside Rg3 enhances glucosestimulated insulin secretion and activates AMPK. Biol Pharm Bull 2008;31:748-51
67. Corton JM, Gillespie JG, Hawley SA, et al. 5-Aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-Activated protein kinase in intact cells? Eur J Biochem 1995;229:558-65
68. Wang YQ, Dong Y, Yao MH. Chromium picolinate inhibits resistin secretion in insulin-resistant 3T3-L1 adipocytes via activation of amp-Activated protein kinase. Clin Exp Pharmacol Physiol 2009;36:843-9
69. Zhang F, Sun C, Wu J, et al. Combretastatin A-4 activates AMP-Activated protein kinase and improves glucose metabolism in db/db mice. Pharmacol Res 2008;57:318-23
70. Park SJ, Ahmad F, Philp A, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 2012;148:421-33
71. Yoon H, Oh YT, Lee JY, et al. Activation of AMP-Activated protein kinase by kainic acid mediates brainderived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells. Biochem Biophys Res Commun 2008;371:495-500
72. Gruzman A, Shamni O, Ben Yakir M, et al. Novel D-xylose derivatives stimulate muscle glucose uptake by activating AMP-Activated protein kinase alpha. J Med Chem 2008;51:8096-108
73. Chen XB, Zhuang JJ, Liu JH, et al. Potential AMPK activators of cucurbitane triterpenoids from Siraitia grosvenorii Swingle. Bioorg Med Chem 2011;19:5776-81
74. Kosaka T, Okuyama R, Sun W, et al. Identification of molecular target of AMP-Activated protein kinase activator by affinity purification and mass spectrometry. Anal Chem 2005;77:2050-5
75. Liu G, Grifman M, Macdonald J, et al. Isoginkgetin enhances adiponectin secretion from differentiated adiposarcoma cells via a novel pathway involving AMP-Activated protein kinase. J Endocrinol 2007;194:569-78
76. Vingtdeux V, Chandakkar P, Zhao H, et al. Novel synthetic small-molecule activators of AMPK as enhancers of autophagy and amyloid-beta peptide degradation. FASEB J 2011;25:219-31
77. Hwang SL, Yang BK, Lee JY, et al. Isodihydrocapsiate stimulates plasma glucose uptake by activation of AMP-Activated protein kinase. Biochem Biophys Res Commun 2008;371:289-93
78. Lian Z, Li Y, Gao J, et al. A novel AMPK activator, WS070117, improves lipid metabolism discords in hamsters and HepG2 cells. Lipids Health Dis 2011;10:67
79. Tan MJ, Ye JM, Turner N, et al. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol 2008;15:263-73
80. Li HB, Ge YK, Zheng XX, et al. Salidroside stimulated glucose uptake in skeletal muscle cells by activating AMP-Activated protein kinase. Eur J Pharmacol 2008;588:165-9.