Akt/PKB activation and insulin signaling: A novel insulin signaling pathway in the treatment of type 2 diabetes

Diabetes, Metabolic Syndrome and Obesity

Volumn 7, Issue , 2014, Pages 55-64

  Mackenzie, Richard W A ^a   Elliott, Bradley T ^a  

^a UNIVERSITY OF WESTMINSTER   (United Kingdom)

Author keywords

5 monophosphate activated protein kinase; Akt PKB; Insulin resistance; Type 2 diabetes

Indexed keywords

ADENYLATE KINASE; DIPHOSPHOINOSITOL PENTAKISPHOSPHATE; INOSITOL HEXAKISPHOSPHATE KINASE 1; INOSITOL PYROPHOSPHATE; INSULIN; ISOENZYME; PROTEIN KINASE; PROTEIN KINASE B; PYROPHOSPHATE; UNCLASSIFIED DRUG;

CELL FUNCTION; CELL GROWTH; DISEASE ASSOCIATION; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SYNTHESIS; GLUCOSE TRANSPORT; HUMAN; INSULIN RESISTANCE; INSULIN SENSITIVITY; METABOLIC DISORDER; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION;

EID: 84894829780     PISSN: None     EISSN: 11787007     Source Type: Journal    
DOI: 10.2147/DMSO.S48260     Document Type: Review

References (83)

1. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365:1333-1346.
2. Basu A, Caumo A, Bettini F, et al. Impaired basal glucose effectiveness in NIDDM: contribution of defects in glucose disappearance and production, measured using an optimized minimal model independent protocol. Diabetes. 1997;46:421-432.
3. Hardie DG, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem. 1998;67:821-855.
4. Hardie DG, Sakamoto K. AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda). 2006;21:48-60.
5. Steinberg GR, Kemp BE. AMPK in health and disease. Physiol Rev. 2009;89:1025-1078.
6. Scott J, Norman D, Hawley S, Kontogiannis L, Hardie D. Protein kinase substrate recognition studied using the recombinant catalytic domain of AMP-activated protein kinase and a model substrate. J Mol Biol. 2002;317:309-323.
7. Sakamoto K, McCarthy A, Smith D, et al. Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J. 2005;24:1810-1820.
8. Xiao B, Sanders MJ, Underwood E, et al. Structure of mammalian AMPK and its regulation by ADP. Nature. 2011;472:230-233.
9. Kramer HF, Witczak CA, Taylor EB, Fujii N, Hirshman MF, Goodyear LJ. AS160 regulates insulin-and contraction-stimulated glucose uptake in mouse skeletal muscle. J Biol Chem. 2006;281:31478-31485.
10. Cartee GD, Wojtaszewski JF. Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated glucose transport. Appl Physiol Nutr Metab. 2007;32:557-566.
11. Chen S, Wasserman DH, MacKintosh C, Sakamoto K. Mice with AS160/TBC1D4-Thr649Ala knockin mutation are glucose intolerant with reduced insulin sensitivity and altered GLUT4 trafficking. Cell Metab. 2011;13:68-79.
12. Ramm G, Larance M, Guilhaus M, James DE. A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160. J Biol Chem. 2006;281:29174-29180.
13. Sano H, Kane S, Sano E, et al. Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation. J Biol Chem. 2003;278:14599-14602.
14. Sakamoto K, Holman GD. Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic. Am J Physiol Endocrinol Metab. 2008;295:E29-E37.
15. Kramer HF, Witczak CA, Fujii N, et al. Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle. Diabetes. 2006;55:2067-2076.
16. Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108:1167-1174.
17. Foretz M, Hébrard S, Leclerc J, et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest. 2010;120: 2355-2369.
18. Musi N, Hirshman MF, Nygren J, et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002;51:2074-2081.
19. DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care. 1992;15:318-368.
20. Turner N, Kowalski GM, Leslie SJ, et al. Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. Diabetologia. 2013;56:1638-1648.
21. Kim YB, Ciaraldi TP, Kong A, et al. Troglitazone but not metformin restores insulin-stimulated phosphoinositide 3-kinase activity and increases p110beta protein levels in skeletal muscle of type 2 diabetic subjects. Diabetes. 2002;51:443-448.
22. Sriwijitkamol A, Coletta DK, Wajcberg E, et al. Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study. Diabetes. 2007;56:836-848.
23. Jing M, Cheruvu VK, Ismail-Beigi F. Stimulation of glucose transport in response to activation of distinct AMPK signaling pathways. Am J Physiol Cell Physiol. 2008;295:C1071-C1082.
24. Goodyear LJ, Giorgino F, Balon TW, Condorelli G, Smith RJ. Effects of contractile activity on tyrosine phosphoproteins and PI 3-kinase activity in rat skeletal muscle. Am J Physiol. 1995;268:E987-E995.
25. Lee AD, Hansen PA, Holloszy JO. Wortmannin inhibits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle. FEBS Lett. 1995;361:51-54.
26. Lund S, Holman GD, Schmitz O, Pedersen, O. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Proc Natl Acad Sci U S A. 1995;92:5817-5821.
27. Yeh JI, Gulve EA, Rameh L, Birnbaum MJ. The effects of wortmannin on rat skeletal muscle. J Biol Chem. 1995;270:2107-2111.
28. Sakamoto K, Arnolds DE, Fujii N, Kramer HF, Hirshman MF, Goodyear LJ. Role of Akt2 in contraction-stimulated cell signaling and glucose uptake in skeletal muscle. Am J Physiol Endocrinol Metab. 2006;291:E1031-E1037.
29. Cartee GD, Douen AG, Ramlal T, Klip A, Holloszy JO. Stimulation of glucose transport in skeletal muscle by hypoxia. J Appl Physiol. 1991;70:1593-1600.
30. Azevedo JL Jr, Carey JO, Pories WJ, Morris PG, Dohm GL. Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscle. Diabetes. 1995;44:695-698.
31. Bergeron R, Russell RR 3rd, Young LH, et al. Effect of AMPK activation on muscle glucose metabolism in conscious rats. Am J Physiol. 1999;276:E938-E944.
32. Hayashi T, Hirshman MF, Kurth EJ, Winder WW, Goodyear LJ. Evidence for 5′ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes. 1998;47:1369-1373.
33. Chakraborty A, Koldobskiy MA, Bello NT, et al. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell. 2010;143:897-910.
34. Musi N, Fujii N, Hirshman MF, et al. AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise. Diabetes. 2001;50:921-927.
35. DeFronzo RA. Pathogenesis of type 2 (non-insulin dependent) diabetes mellitus: a balanced overview. Diabetologia. 1992;35:389-397.
36. Højlund K, Mustard KJ, Staehr P, et al. AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes. Am J Physiol Endocrinol Metab. 2004;286: E239-E244.
37. McBride A, Ghilagabe S, Nikolaev A, Hardie DG. The glycogen-binding domain on the AMPK # subunit allows the kinase to act as a glycogen sensor. Cell Metab. 2009;9:23-34.
38. McBride A, Ghilagaber S, Nikolaev A, Hardie DG. Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. Biochem Soc Trans. 2003;31:216-219.
39. Mu J, Brozinick JT Jr, Valladares O, Bucan M, Birnbaum MJ. A role for AMP-activated protein kinase in contraction-and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell. 2001;7:1085-1094.
40. Fujii N, Ho RC, Manabe Y, et al. Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice. Diabetes. 2008;57:2958-2966.
41. Jensen TE, Wojtaszewski JFP, Richter EA. AMP-activated protein kinase in contraction regulation of skeletal muscle metabolism: necessary and/or sufficient? Acta Physiol (Oxf). 2009;196:155-174.
42. Hunter RW, Treebak JT, Wojtaszewski JF, Sakamoto, K. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Diabetes. 2011;60:766-774.
43. Kennedy JW, Hirshman MF, Gervino EV, et al. Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes. 1999;48:1192-1197.
44. Gonzalez E, McGraw TE. Insulin-modulated Akt subcellular localization determines Akt isoform-specific signaling. Proc Natl Sci Acad U S A. 2009;106:7004-7009.
45. Manning BD. Insulin signaling: inositol phosphates get into the Akt. Cell. 2010;143(6):861-863.
46. Stein SC, Woods A, Jone NA, Davison MD, Carling D. The regulation of AMP-activated protein kinase by phosphorylation. Biochem J. 2000;345:437-443.
47. Hawley SA, Pan DA, Mustard KJ, et al. Calmodulin-dependent protein kinase kinase-[beta] is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2005;2:9-19.
48. Faissner A, Heck N, Dobbertin A, Garwood J. DSD-1-proteoglycan/phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of neural tissues. Adv Exp Med Biol. 2006;557:25-53.
49. Lai KM, Gonzalez M, Poueymirou WT, et al. Conditional activation of AKT in adult skeletal muscle induces rapid hypertrophy. Mol Cell Biol. 2004;24:9295-9304.
50. Garofalo RS, Orena SJ, Rafidi K, et al. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J Clin Invest. 2003;112:197-208.
51. Easton RM, Cho H, Roovers K, et al. Role for Akt3/protein kinase Bgamma in attainment of normal brain size. Mol Cell Biol. 2005;25: 1869-1878.
52. Mora A, Komander D, van Aalten DM, Alessi DR. PDK1, the master regulator of AGC kinase signal transduction. Semin Cell Dev Biol. 2004;15:161-170.
53. Howlett KF, Sakamoto K, Garnham A, Cameron-Smith D, Hargreave M. Resistance exercise and insulin regulate AS160 and interaction with 14-3-3 in human skeletal muscle. Diabetes. 2007;56:1608-1614.
54. Kohn AD, Summers SA, Birnbaum MJ, Roth RA. Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J Biol Chem. 1996;271:31372-31378.
55. Lu M, Wan M, Leavens KF, et al. Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. Nat Med. 2012;18: 388-395.
56. Zick Y. Insulin resistance: a phosphorylation-based uncoupling of insulin signaling. Trends Cell Biol. 2001;11:437-441.
57. Tremblay F, Lavigne C, Jacques H, Marette A. Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat-fed rats is associated with alterations in both Akt/protein kinase B and atypical protein kinase C activities. Diabetes. 2001;50:1901-1910.
58. Karlsson HK, Zierath JR, Kane S, Krook A, Lienhard GE, Wallberg-Henriksson H. Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects. Diabetes. 2005;54:1692-1697.
59. Cho H, Mu J, Kim JK, et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science. 2001;292:1728-1731.
60. George S, Rochford JJ, Wolfrum C, et al. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science. 2004;304:1325-1328.
61. Harrington LS, Findlay GM, Lamb RF. Restraining PI3K: mTOR signalling goes back to the membrane. Trends Biochem Sci. 2005;30:35-42.
62. Calleja V, Alcor D, Laguerre M, et al. Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo. PLoS Biol. 2007;5:e95.
63. Werner JK Jr, Speed T, Bhandari R. Protein pyrophosphorylation by diphosphoinositol pentakisphosphate (InsP7). Methods Mol Biol. 2009;645:87-102.
64. Barker CJ, Illies C, Gaboardi GC, Berggren PO. Inositol pyrophosphates: structure, enzymology and function. Cell Mol Life Sci. 2009;66: 3851-3871.
65. Nagata E, Luo HR, Saiardi A, Bae BI, Suzuki N, Snyder SH. Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death. J Biol Chem. 2005;280:1634-1640.
66. Saiardi A, Nagata E, Luo HR, Snowman AM, Snyder SH. Identification and characterization of a novel inositol hexakisphosphate kinase. J Biol Chem. 2001;276:39179-39185.
67. Weiss EP, Racette SB, Villareal DT, et al. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am J Clin Nutr. 2006;84:1033-1042.
68. Padmanabhan U, Dollins DE, Fridy PC, York JD, Downes CP. Characterization of a selective inhibitor of inositol hexakisphosphate kinases: use in defining biological roles and metabolic relationships of inositol pyrophosphates. J Biol Chem. 2009;284:10571-10582.
69. Bhandari R, Juluri KR, Resnick AC, Snyder SH. Gene deletion of inositol hexakisphosphate kinase 1 reveals inositol pyrophosphate regulation of insulin secretion, growth, and spermiogenesis. Proc Natl Acad Sci U S A. 2008;105:2349-2353.
70. Reynolds T 4th, Brozinick JT, Rogers MA, Cushman SW. Mechanism of hypoxia-stimulated glucose transport in rat skeletal muscle: potential role of glycogen. Am J Physiol. 1998;274:E773-E778.
71. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378:785-789.
72. Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9:367-377.
73. Kaidanovich O, Eldar-Finkelman H. The role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes. Expert Opin Ther Targets. 2002;6:555-561.
74. Peng XD, Xu PZ, Chen ML, et al. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 2003;17: 1352-1365.
75. Elchebly M, Payette P, Michaliszyn E, et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science. 1999;283:1544-1548.
76. Illies C, Gromada J, Fiume R, et al. Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic beta cells. Science. 2007;318:1299-1302.
77. Utzschneider KM, Prigeon RL, Carr DB, et al. Impact of differences in fasting glucose and glucose tolerance on the hyperbolic relationship between insulin sensitivity and insulin responses. Diabetes Care. 2006;29:356-362.
78. Ross SE, Hemati N, Longo KA, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000;289:950-953.
79. Izumiya Y, Hopkins T, Morris C, et al. Fast/glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab. 2008;7:159-172.
80. Stål O, Pérez-Tenorio G, Akerberg L, et al. Akt kinases in breast cancer and the results of adjuvant therapy. Breast Cancer Res. 2003;5: R37-R44.
81. Stahl JM, Sharma A, Cheung M, et al. Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 2004;64: 7002-7010.
82. Park HU, Suy S, Danner M, et al. AMP-activated protein kinase promotes human prostate cancer cell growth and survival. Mol Cancer Ther. 2009;8:733-741.
83. Decensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010;3:1451-1461.