Tissue-specific insulin signaling in the regulation of metabolism and aging

IUBMB Life

Volumn 66, Issue 7, 2014, Pages 485-495

  Zhang, Jingjing ^a   Liu, Feng ^a,b  

^a CENTRAL SOUTH UNIVERSITY   (China)

^b UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

Author keywords

aging; insulin signaling; metabolism; tissue specific

Indexed keywords

GLUCOSE; INSULIN; INSULIN RECEPTOR; SOMATOMEDIN C;

AGING; CELL SURVIVAL; FATTY ACID TRANSPORT; GLUCONEOGENESIS; GLUCOSE HOMEOSTASIS; GLUCOSE TRANSPORT; HOMEOSTASIS; HUMAN; INSULIN RELEASE; LIFESPAN; LIPOGENESIS; METABOLIC REGULATION; NERVE CELL; NONHUMAN; PANCREAS ISLET BETA CELL; REVIEW; SIGNAL TRANSDUCTION; TISSUE SPECIFICITY; ADIPOSE TISSUE; ANIMAL; ANTIBODY SPECIFICITY; CARBOHYDRATE METABOLISM; ENERGY METABOLISM; LIPID METABOLISM; LIVER; METABOLISM; PHYSIOLOGY; SKELETAL MUSCLE;

ANIMALIA; MAMMALIA; MUS; NEMATODA;

ADIPOSE TISSUE; AGING; ANIMALS; CARBOHYDRATE METABOLISM; ENERGY METABOLISM; HUMANS; INSULIN; LIPID METABOLISM; LIVER; MUSCLE, SKELETAL; ORGAN SPECIFICITY; SIGNAL TRANSDUCTION;

EID: 84906338070     PISSN: 15216543     EISSN: 15216551     Source Type: Journal    
DOI: 10.1002/iub.1293     Document Type: Review

References (156)

1. Sharma, M. D., Garber, A. J., and, Farmer, J. A., (2008) Role of insulin signaling in maintaining energy homeostasis. Endocr. Pract. 14, 373-380.
2. Kadowaki, T., (2000) Insights into insulin resistance and type 2 diabetes from knockout mouse models. J. Clin. Invest. 106, 459-465.
3. Katic, M., and, Kahn, C. R., (2005) The role of insulin and IGF-1 signaling in longevity. Cell. Mol. Life Sci. 62, 320-343.
4. Porte, D. Jr,., Baskin, D. G., and, Schwartz, M. W., (2005) Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. Elegans to humans. Diabetes 54, 1264-1276.
5. Saltiel, A. R., and, Kahn, C. R., (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414, 799-806.
6. Ryu J, Galan AK, Xin X, Dong F, Abdul-Ghani MA, Zhou L, Wang C, Li C, Holmes BM, Sloane LB, Austad SN, Guo S, Musi N, DeFronzo RA, Deng C, White MF, Liu F, Dong LQ,. (2014) APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor. Cell Report, 7 (4); 1227-1238.
7. Kim, E. K., and, Choi, E. J., (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802, 396-405.
8. Lim, M. A., Riedel, H., and, Liu, F., (2004) Grb10: more than a simple adaptor protein. Front. Biosci. 9, 387-403.
9. Holt, L. J., and, Siddle, K., (2005) Grb10 and Grb14: enigmatic regulators of insulin action-and more? Biochem. J. 388, 393-406.
10. Copps, K. D., and, White, M. F., (2012) Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia 55, 2565-2582.
11. Guo, S., (2014) Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms. J. Endocrinol. 220, T1-T23.
12. Tiganis, T., (2013) PTP1B and TCPTP-nonredundant phosphatases in insulin signaling and glucose homeostasis. FEBS J. 280, 445-458.
13. Lewis, G. F., Vranic, M., and, Giacca, A., (1997) Glucagon enhances the direct suppressive effect of insulin on hepatic glucose production in humans. Am. J. Physiol. 272, E371-E378.
14. Liljenquist, J. E., Mueller, G. L., Cherrington, A. D., Keller, U., Chiasson, J.-L., et al. (1977) Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man. J. Clin. Invest. 59, 369-374.
15. Hendrick, G. K., Frizzell, R. T., Williams, P. E., and, Cherrington, A. D., (1990) Effect of hyperglucagonemia on hepatic glycogenolysis and gluconeogenesis after a prolonged fast. Am. J. Physiol. 258, E841-E849.
16. Mittelman, S. D., and, Bergman, R. N., (2000) Inhibition of lipolysis causes suppression of endogenous glucose production independent of changes in insulin. Am. J. Physiol. Endocrinol. Metab. 279, E630-E637.
17. Rebrin, K., Steil, G. M., Mittelman, S. D., and, Bergman, R. N., (1996) Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J. Clin. Invest. 98, 741-749.
18. Sindelar, D. K., Chu, C. A., Rohlie, M., Neal, D. W., Swift, L. L., et al., (1997) The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog. Diabetes 46, 187-196.
19. Inoue, H., Ogawa, W., Asakawa, A., Okamoto, Y., Nishizawa, A., et al. (2006) Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. Cell Metab. 3, 267-275.
20. Konner, A. C., Janoschek, R., Plum, L., Jordan, S. D., Rother, E., et al. (2007) Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. Cell Metab. 5, 438-449.
21. Michael, M. D., Kulkarni, R. N., Postic, C., Previs, S. F., Shulman, G. I., et al. (2000) Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol. Cell 6, 87-97.
22. Kubota, N., Kubota, T., Itoh, S., Kumagai, H., Kozono, H., et al. (2008) Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding. Cell. Metab. 8, 49-64.
23. Guo, S., Copps, K. D., Dong, X., Park, S., Cheng, Z., et al. (2009) The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic nutrient homeostasis. Mol. Cell. Biol. 29, 5070-5083.
24. Cheng, Z., Guo, S., Copps, K., Dong, X., Kollipara, R., et al. (2009) Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat. Med. 15, 1307-1311.
25. DeFronzo, R. A., Jacot, E., Jequier, E., Maeder, E., Wahren, J., et al. (1981) The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 30, 1000-1007.
26. Kristiansen, S., Hargreaves, M., and, Richter, E. A., (1996) Exercise-induced increase in glucose transport, GLUT-4, and VAMP-2 in plasma membrane from human muscle. Am. J. Physiol. 270, E197-E201.
27. Blaak, E. E., (2005) Metabolic fluxes in skeletal muscle in relation to obesity and insulin resistance. Best Pract. Res. Clin. Endocrinol. Metab. 19, 391-403.
28. Bruning, J. C., Michael, M. D., Winnay, J. N., Hayashi, T., Hörsch, D., et al. (1998) A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol. Cell. 2, 559-569.
29. DeFronzo, R. A., Gunnarsson, R., Björkman, O., Olsson, M., and, Wahren, J., (1985) Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J. Clin. Invest. 76, 149-155.
30. Rabol, R., Petersen, K. F., Dufour, S., Flannery, C., Shulman, G. I., (2011) Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc. Natl. Acad. Sci. USA. 108, 13705-13709.
31. Krook, A., Björnholm, M., Galuska, D., Jiang, X. J., Fahlman, R., et al. (2000) Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients. Diabetes 49, 284-292.
32. Zierath, J. R., He, L., Gumà, A., Odegoard Wahlström, E., Klip, A., et al. (1996) Insulin action on glucose transport and plasma membrane GLUT4 content in skeletal muscle from patients with NIDDM. Diabetologia 39, 1180-1189.
33. Kim, J. K., Michael, M. D., Previs, S. F., Peroni, O. D., Mauvais-Jarvis, F., et al. (2000) Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. J. Clin. Invest. 105, 1791-1797.
34. Long, Y. C., Cheng, Z., Copps, K. D., and, White, M. F., (2011) Insulin receptor substrates Irs1 and Irs2 coordinate skeletal muscle growth and metabolism via the Akt and AMPK pathways. Mol. Cell. Biol. 31, 430-441.
35. Powell, D. J., Turban, S., Gray, A., Hajduch, E., and, Hundal, H. S., (2004) Intracellular ceramide synthesis and protein kinase Czeta activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells. Biochem. J. 382, 619-629.
36. Turcotte, L. P., and, Fisher, J. S., (2008) Skeletal muscle insulin resistance: roles of fatty acid metabolism and exercise. Phys. Ther. 88, 1279-1296.
37. Pedersen, B. K., and, Febbraio, M. A., (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat. Rev. Endocrinol. 8, 457-465.
38. Pedersen, B. K., (2009) The diseasome of physical inactivity-and the role of myokines in muscle-fat cross talk. J. Physiol. 587, 5559-5568.
39. Park, K. H., Zaichenko, L., Brinkoetter, M., Thakkar, B., Sahin-Efe, A., et al. (2013) Circulating irisin in relation to insulin resistance and the metabolic syndrome. J. Clin. Endocrinol. Metab. 98, 4899-4907.
40. Bostrom, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., et al. (2012) A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463-468.
41. Guo, T., Bond, N. D., Jou, W., Gavrilova, O., Portas, J., et al. (2012) Myostatin inhibition prevents diabetes and hyperphagia in a mouse model of lipodystrophy. Diabetes 61, 2414-2423.
42. Rosen, E. D., and, Spiegelman, B. M., (2014) What we talk about when we talk about fat. Cell 156, 20-44.
43. Yki-Jarvinen, H., (2005) Fat in the liver and insulin resistance. Ann. Med. 37, 347-356.
44. Chao, L., Marcus-Samuels, B., Mason, M. M., Moitra, J., Vinson, C., et al. (2000) Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones. J. Clin. Invest. 106, 1221-1228.
45. Penkov, D. N., Egorov, A. D., Mozgovaya, M. N., and, Tkachuk, V. A., (2013) Insulin resistance and adipogenesis: role of transcription and secreted factors. Biochemistry 78, 8-18.
46. DeFronzo, R. A., Bonadonna, R. C., and, Ferrannini, E., (1992) Pathogenesis of NIDDM. A balanced overview. Diabetes Care 15, 318-368.
47. Frayn, K. N., (2002) Adipose tissue as a buffer for daily lipid flux. Diabetologia 45, 1201-1210.
48. Coppack, S. W., Patel, J. N., and, Lawrence, V. J., (2001) Nutritional regulation of lipid metabolism in human adipose tissue. Exp. Clin. Endocrinol. Diabetes 109, S202-S214.
49. Czech, M. P., Tencerova, M., Pedersen, D. J., and, Aouadi, M., (2013) Insulin signalling mechanisms for triacylglycerol storage. Diabetologia 56. 949-964.
50. Bluher, M., Michael, M. D., Peroni, O. D., Ueki, K., Carter, N., et al. (2002) Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev. Cell 3, 25-38.
51. Dimitriadis, G., Mitrou, P., Lambadiari, V., Maratou, E., and, Raptis, S. A., (2011) Insulin effects in muscle and adipose tissue. Diab. Res. Clin. Pract. 93, S52-S59.
52. Dimitriadis, G., Mitrou, P., Lambadiari, V., Boutati, E., Maratou, E., et al. (2006) Glucose and lipid fluxes in the adipose tissue after meal ingestion in hyperthyroidism. J. Clin. Endocrinol. Metab. 91, 1112-1118.
53. Newsholme, E. A., and, Dimitriadis, G., (2001) Integration of biochemical and physiologic effects of insulin on glucose metabolism. Exp. Clin. Endocrinol. Diabetes 109, S122-S134.
54. Shepherd, P. R., and, Kahn, B. B., (1999) Glucose transporters and insulin action-implications for insulin resistance and diabetes mellitus. N. Engl. J. Med. 341, 248-257.
55. Pause, A., Belsham, G. J., Gingras, A. C., Donzé, O., Lin, T. A., et al. (1994) Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5′-cap function. Nature 371, 762-767.
56. Duvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., et al. (2010) Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell 39, 171-183.
57. Kim, J. B., Sarraf, P., Wright, M., Yao, K. M., Mueller, E., et al. (1998) Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J. Clin. Invest. 101, 1-9.
58. Lu, M., Wan, M., Leavens, K. F., Chu, Q., Monks, B. R., et al. (2012) Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. Nat. Med. 18, 388-395.
59. Foretz, M., Pacot, C., Dugail, I., Lemarchand, P., Guichard, C., et al. (1999) ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. Mol. Cell. Biol. 19, 3760-3768.
60. Shimomura, I., Bashmakov, Y., Ikemoto, S., Horton, J. D., Brown, M. S., et al. (1999) Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Proc. Natl. Acad. Sci. USA 96, 13656-13661.
61. Herman, M. A., Peroni, O. D., Villoria, J., Schön, M. R., Abumrad, N. A., et al. (2012) A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature 484, 333-338.
62. Bae, E. J., Xu, J., Oh, D. Y., Bandyopadhyay, G., Lagakos, W. S., et al. (2012) Liver-specific p70 S6 kinase depletion protects against hepatic steatosis and systemic insulin resistance. J. Biol. Chem. 287, 18769-18780.
63. Li, S., Ogawa, W., Emi, A., Hayashi, K., Senga, Y., et al. (2011) Role of S6K1 in regulation of SREBP1c expression in the liver. Biochem. Biophys. Res. Commun. 412, 197-202.
64. Ahmad, F., Lindh, R., Tang, Y., Ruishalme, I., Ost, A., et al. (2009) Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the beta3-adrenergic receptor agonist CL316243: effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes. Biochem. J. 424, 399-410.
65. Choi, S. M., Tucker, D. F., Gross, D. N., Easton, R. M., DiPilato, L. M., et al. (2010) Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway. Mol. Cell. Biol. 30, 5009-5020.
66. Duncan, R. E., Sarkadi-Nagy, E., Jaworski, K., Ahmadian, M., and, Sul, H. S., (2008) Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA). J. Biol. Chem. 283, 25428-25436.
67. Jaworski, K., Ahmadian, M., Duncan, R. E., Sarkadi-Nagy, E., Varady, K. A., et al. (2009) AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency. Nat. Med. 15, 159-168.
68. Chakrabarti, P., and, Kandror, K. V., (2009) FoxO1 controls insulin-dependent adipose triglyceride lipase (ATGL) expression and lipolysis in adipocytes. J. Biol. Chem. 284, 13296-13300.
69. Eguchi, J., Wang, X., Yu, S., Kershaw, E. E., Chiu, P. C., et al. (2011) Transcriptional control of adipose lipid handling by IRF4. Cell. Metab. 13, 249-259.
70. Armoni, M., Harel, C., Karni, S., Chen, H., Bar-Yoseph, F., et al. (2006) FOXO1 represses peroxisome proliferator-activated receptor-gamma1 and -gamma2 gene promoters in primary adipocytes. A novel paradigm to increase insulin sensitivity. J. Biol. Chem. 281, 19881-19891.
71. Puri, V., Konda, S., Ranjit, S., Aouadi, M., Chawla, A., et al. (2007) Fat-specific protein 27, a novel lipid droplet protein that enhances triglyceride storage. J. Biol. Chem. 282, 34213-34218.
72. Kim, J. Y., Liu, K., Zhou, S., Tillison, K., Wu, Y., et al. (2008) Assessment of fat-specific protein 27 in the adipocyte lineage suggests a dual role for FSP27 in adipocyte metabolism and cell death. Am. J. Physiol. Endocrinol. Metab. 294, E654-E667.
73. Kopelman, P. G., (2000) Obesity as a medical problem. Nature 404, 635-643.
74. Nishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., et al. (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med. 15, 914-20.
75. Minamino, T., Orimo, M., Shimizu, I., Kunieda, T., Yokoyama, M., et al. (2009) A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat. Med. 15, 1082-1087.
76. Smith, U., (2002) Impaired ('diabetic') insulin signaling and action occur in fat cells long before glucose intolerance-is insulin resistance initiated in the adipose tissue? Int. J. Obes. Relat. Metab. Disord. 26, 897-904.
77. Bluher, M., Kahn, B. B., and, Kahn, C. R., (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299, 572-574.
78. Lowell, B. B., S-Susulic, V., Hamann, A., Lawitts, J. A., Himms-Hagen, J., et al. (1993) Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366, 740-742.
79. Guerra, C., Navarro, P., Valverde, A. M., Arribas, M., Brüning, J., et al. (2001) Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance. J. Clin. Invest. 108, 1205-1213.
80. Abel, E. D., Peroni, O., Kim, J. K., Kim, Y. B., Boss, O., et al. (2001) Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 409, 729-733.
81. Wang, Q., and, Jin, T., (2009) The role of insulin signaling in the development of beta-cell dysfunction and diabetes. Islets 1, 95-101.
82. Best, C. H., and, Haist, R. E., (1941) The effect of insulin administration on the insulin content of the pancreas. J. Physiol. 100, 142-146.
83. Leibiger, I. B., Leibiger, B., and, Berggren, P. O., (2002) Insulin feedback action on pancreatic beta-cell function. FEBS Lett. 532m 1-6.
84. Leibiger, I. B., Leibiger, B., Berggren, P. O., (2008) Insulin signaling in the pancreatic beta-cell. Annu. Rev. Nutr. 28, 233-251.
85. Xu, G. G., and, Rothenberg, P. L., (1998) Insulin receptor signaling in the beta-cell influences insulin gene expression and insulin content: evidence for autocrine beta-cell regulation. Diabetes 47, 1243-1252.
86. Kubota, N., Terauchi, Y., Tobe, K., Yano, W., Suzuki, R., et al. (2004) Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus. J. Clin. Invest. 114, 917-927.
87. Kulkarni, R. N., Brüning, J. C., Winnay, J. N., Postic, C., Magnuson, M. A., et al. (1999) Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96, 329-339.
88. Kulkarni, R. N., Winnay, J. N., Daniels, M., Brüning, J. C., Flier, S. N., et al. (1999) Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines. J. Clin. Invest. 104, R69-R75.
89. Withers, D. J., Gutierrez, J. S., Towery, H., Burks, D. J., Ren, J. M., et al. (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391, 900-904.
90. Otani, K., Kulkarni, R. N., Baldwin, A. C., Krutzfeldt, J., Ueki, K., et al. (2004) Reduced beta-cell mass and altered glucose sensing impair insulin-secretory function in betaIRKO mice. Am. J. Physiol. Endocrinol. Metab. 286, E41-E49.
91. Cantley, J., Choudhury, A. I., Asare-Anane, H., Selman, C., Lingard, S., et al. (2007) Pancreatic deletion of insulin receptor substrate 2 reduces beta and alpha cell mass and impairs glucose homeostasis in mice. Diabetologia 50, 1248-1256.
92. Tuttle, R. L., Gill, N. S., Pugh, W., Lee, J. P., Koeberlein, B., et al. (2001) Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha. Nat. Med. 7, 1133-1137.
93. Rhodes, C. J., White, M. F., Leahy, J. L., and, Kahn, S. E., (2013) Direct autocrine action of insulin on beta-cells: does it make physiological sense? Diabetes 62, 2157-2163.
94. Zick, Y., (2005) Ser/Thr phosphorylation of IRS proteins: a molecular basis for insulin resistance. Sci STKE 2005, pe4.
95. Miller, R. E., (1981) Pancreatic neuroendocrinology: peripheral neural mechanisms in the regulation of the Islets of Langerhans. Endocr. Rev. 2, 471-494.
96. Porte, D. Jr,. (1969) Sympathetic regulation of insulin secretion. Its relation to diabetes mellitus. Arch. Intern. Med. 123, 252-260.
97. Kulkarni, R. N., Holzenberger, M., Shih, D. Q., Ozcan, U., Stoffel, M., et al. (2002) Beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. Nat. Genet. 31, 111-115.
98. Ueki, K., Okada, T., Hu, J., Liew, C. W., Assmann, A., et al. (2006) Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes. Nat. Genet. 38, 583-588.
99. Wicksteed, B., Brissova, M., Yan, W., Opland, D. M., Plank, J. L., et al. (2010) Conditional gene targeting in mouse pancreatic ss-Cells: analysis of ectopic Cre transgene expression in the brain. Diabetes 59, 3090-3098.
100. Song, J., Xu, Y., Hu, X., Choi, B., and, Tong, Q., (2010) Brain expression of Cre recombinase driven by pancreas-specific promoters. Genesis 48, 628-634.
101. Lee, J. Y., Ristow, M., Lin, X., White, M. F., Magnuson, M. A., et al. (2006) RIP-Cre revisited, evidence for impairments of pancreatic beta-cell function. J. Biol. Chem. 281, 2649-2653.
102. Gerozissis, K., (2003) Brain insulin: regulation, mechanisms of action and functions. Cell. Mol. Neurobiol. 23, 1-25.
103. Plum, L., Schubert, M., and, Bruning, J. C., (2005) The role of insulin receptor signaling in the brain. Trends Endocrinol. Metab. 16, 59-65.
104. Duarte, A. I., Moreira, P. I., and, Oliveira, C. R., (2012) Insulin in central nervous system: more than just a peripheral hormone. J. Aging Res. 2012, 384017.
105. van der Heide, L. P., Ramakers, G. M., and, Smidt, M. P., (2006) Insulin signaling in the central nervous system: learning to survive. Prog. Neurobiol. 79, 205-221.
106. Woods, S. C., Lotter, E. C., McKay, L. D., Porte, D. Jr,. (1979) Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 282, 503-505.
107. Kim, Y. I., Bandyopadhyay, J., Cho, I., Lee, J., Park, D. H., et al. (2014) Nucleolar GTPase NOG-1 Regulates Development, Fat Storage, and Longevity through Insulin/IGF Signaling in C. Elegans. Mol. Cells 37, 51-58.
108. Tatar, M., Kopelman, A., Epstein, D., Tu, M. P., Yin, C. M., et al. (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292, 107-110.
109. Bruning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., et al. (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289, 2122-2125.
110. Taguchi, A., Wartschow, L. M., and, White, M. F., (2007) Brain IRS2 signaling coordinates life span and nutrient homeostasis. Science 317, 369-372.
111. Zemva, J., Udelhoven, M., Moll, L., Freude, S., Stöhr, O., et al. (2013) Neuronal overexpression of insulin receptor substrate 2 leads to increased fat mass, insulin resistance, and glucose intolerance during aging. Age 35, 1881-1897.
112. Milanski, M., Arruda, A. P., Coope, A., Ignacio-Souza, L. M., Nunez, C. E., et al. (2012) Inhibition of hypothalamic inflammation reverses diet-induced insulin resistance in the liver. Diabetes 61, 1455-1462.
113. Barbieri, M., Bonafè, M., Franceschi, C., and, Paolisso, G., (2003) Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am. J. Physiol. Endocrinol. Metab. 285, E1064-E1071.
114. Kenyon, C., Chang, J., Gensch, E., Rudner, A., and, Tabtiang, R., (1993) A C. Elegans mutant that lives twice as long as wild type. Nature 366, 461-464.
115. Hwangbo, D. S., Gershman, B., Tu, M. P., Palmer, M., and, Tatar, M., (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429, 562-566.
116. Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., et al. (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421, 182-187.
117. Roth, G. S., Lane MA, Ingram DK, Mattison JA, Elahi D, et al. (2002) Biomarkers of caloric restriction may predict longevity in humans. Science 297, 811.
118. Suh, Y., Atzmon, G., Cho, M.-O., Hwang, D., Liu, B., et al. (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc. Natl. Acad. Sci. USA 105, 3438-3442.
119. Ayyadevara, S., Alla, R., Thaden, J. J., and, Shmookler Reis, R. J., (2008) Remarkable longevity and stress resistance of nematode PI3K-null mutants. Aging Cell 7, 13-22.
120. Murakami, S., and, Johnson, T. E., (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143, 1207-1218.
121. Taub, J., Lau, J. F., Ma, C., Hahn, J. H., Hoque, R., et al. (1999) A cytosolic catalase is needed to extend adult lifespan in C. Elegans daf-C and clk-1 mutants. Nature 399, 162-166.
122. Fabrizio, P., Liou, L. L., Moy, V. N., Diaspro, A., Valentine, J. S., et al. (2003) SOD2 functions downstream of Sch9 to extend longevity in yeast. Genetics 163, 35-46.
123. Clancy, D. J., Gems, D., Harshman, L. G., Oldham, S., Stocker, H., et al. (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292, 104-106.
124. Cohen, E., Bieschke, J., Perciavalle, R. M., Kelly, J. W., and, Dillin, A., (2006) Opposing activities protect against age-onset proteotoxicity. Science 313, 1604-1610.
125. Wanagat, J., Allison, D. B., and, Weindruch, R., (1999) Caloric intake and aging: mechanisms in rodents and a study in nonhuman primates. Toxicol. Sci. 52, 35-40.
126. Dunn, S. E., Kari, F. W., French, J., Leininger, J. R., Travlos, G., et al. (1997) Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. Cancer Res. 57, 4667-4672.
127. Brussee, V., Cunningham, F. A., and, Zochodne, D. W., (2004) Direct insulin signaling of neurons reverses diabetic neuropathy. Diabetes 53, 1824-1830.
128. Zhao, W. Q., Chen, H., Quon, M. J., and, Alkon, D. L., (2004) Insulin and the insulin receptor in experimental models of learning and memory. Eur. J. Pharmacol., 490, 71-81.
129. Schubert, M., Gautam, D., Surjo, D., Ueki, K., Baudler, S., et al. (2004) Role for neuronal insulin resistance in neurodegenerative diseases. Proc. Natl. Acad. Sci. USA 101, 3100-3105.
130. Liu, Y., Liu, F., Grundke-Iqbal, I., Iqbal, K., and, Gong, C. X., (2011) Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes. J. Pathol. 225, 54-62.
131. Bomfim, T. R., Forny-Germano, L., Sathler, L. B., Brito-Moreira, J., Houzel, J. C., et al. (2012) An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated Abeta oligomers. J. Clin. Invest. 122, 1339-1353.
132. Carvalho, C., Cardoso, S., Correia, S. C., Santos, R. X., Santos, M. S., et al. (2012) Metabolic alterations induced by sucrose intake and Alzheimer's disease promote similar brain mitochondrial abnormalities. Diabetes 61, 1234-1242.
133. Huang, T. J., Price, S. A., Chilton, L., Calcutt, N. A., Tomlinson, D. R., et al. (2003) Insulin prevents depolarization of the mitochondrial inner membrane in sensory neurons of type 1 diabetic rats in the presence of sustained hyperglycemia. Diabetes 52, 2129-2136.
134. Freude, S., Hettich, M. M., Schumann, C., Stöhr, O., Koch, L., et al. (2009) Neuronal IGF-1 resistance reduces Abeta accumulation and protects against premature death in a model of Alzheimer's disease. FASEB J. 23, 3315-3324.
135. Heilbronn, L. K., and, Ravussin, E., (2003) Calorie restriction and aging: review of the literature and implications for studies in humans. Am. J. Clin. Nutr. 78, 361-369.
136. Harrison, D. E., Archer, J. R., and, Astle, C. M., (1984) Effects of food restriction on aging: separation of food intake and adiposity. Proc. Natl. Acad. Sci. USA 81, 1835-1838.
137. Wolkow, C. A., Kimura, K. D., Lee, M. S., and, Ruvkun, G., (2000) Regulation of C. Elegans life-span by insulin like signaling in the nervous system. Science 290, 147-50.
138. Kimura, K. D., Tissenbaum, H. A., Liu, Y., and, Ruvkun, G., (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942-946.
139. Blagosklonny, M. V., and, Hall, M. N., (2009) Growth and aging: a common molecular mechanism. Aging 1, 357-362.
140. Wang, X., and, Proud, C. G., (2006) The mTOR pathway in the control of protein synthesis. Physiology 21, 362-369.
141. Mizushima, N., Levine, B., Cuervo, A. M., and, Klionsky, D. J., (2008) Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075.
142. Gingras, A. C., Raught, B., and, Sonenberg, N., (1999) eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu. Rev. Biochem. 68, 913-963.
143. Kaeberlein, M., and, Kennedy, B. K., (2011) Hot topics in aging research: protein translation and TOR signaling, 2010. Aging Cell 10, 185-190.
144. Kaeberlein, M., and, Kennedy, B. K., (2007) Protein translation, 2007. Aging Cell 6, 731-734.
145. Laplante, M., and, Sabatini, D. M., (2012) mTOR signaling in growth control and disease. Cell 149, 274-293.
146. Magnuson, B., Ekim, B., and, Fingar, D. C., (2012) Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem. J. 441, 1-21.
147. Bonawitz, N. D., Chatenay-Lapointe, M., Pan, Y., and, Shadel, G. S., (2007) Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression. Cell Metab. 5, 265-277.
148. Kaeberlein, M., Powers, R. W., 3rd, Steffen, K. K., Westman, E. A., Hu, D., et al. (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193-1196.
149. Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L., et al. (2003) Genetics: influence of TOR kinase on lifespan in C. Elegans. Nature 426, 620.
150. Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., et al. (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14, 885-890.
151. Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392-395.
152. Blagosklonny, M. V., (2012) Prospective treatment of age-related diseases by slowing down aging. Am. J. Pathol. 181, 1142-1146.
153. Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J. H., Hsu, P. P., et al. (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell 22, 159-168.
154. Kaeberlein, M., (2013) mTOR inhibition: from aging to autism and beyond. Scientifica 2013, 849186.
155. Liu M, Bai J, He S, Villarreal R, Hu D, Zhang C, Yang X, Liang H, Slaga TJ, Yu Y, Zhou Z, Blenis J, Scherer PE, Dong LQ, Liu F,. (2014) Grb10 Promotes Lipolysis and Thermogenesis by Phosphorylationdependent Feedback Inhibition of mTORC1. Cell Metab, 19 (6); 967-980.
156. Polak, P., et al. (2008) Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab. 8, 399-410.