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Journal of Cachexia, Sarcopenia and Muscle
Published in: Journal of Cachexia, Sarcopenia and Muscle 1/2012

Open Access 01-03-2012 | Review

The role of insulin resistance in the development of muscle wasting during cancer cachexia

Authors: Mary A. Honors, Kimberly P. Kinzig

Published in: Journal of Cachexia, Sarcopenia and Muscle | Issue 1/2012

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Abstract

Background

Cancer cachexia is a complex syndrome associated with multiple metabolic abnormalities. Insulin resistance is present in many cancer patients and may be one mechanism through which muscle wasting occurs.

Methods and results

The present review examines evidence in support of a role for insulin resistance in the development of muscle wasting during cancer cachexia and identifies areas for future research. Patients suffering from cancer cachexia tend to exhibit insulin resistance and improvements in insulin resistance have the potential to improve cachexia symptoms. In addition, evidence suggests that insulin resistance may occur prior to the onset of cachexia symptoms.

Conclusions

Further investigation of the role of insulin resistance in cancer cachexia is needed. The use of translational research in this area is strongly encouraged, and has important implications for clinical research and the treatment and prevention of cancer cachexia.
Literature
1.
2.
Kolter DP. Cachexia. Ann Intern Med. 2000;133:622–34.
3.
Argiles JM, Alvarez B, Lopez-Soriano FJ. The metabolic basis of cancer cachexia. Med Res Rev. 1997;17:477–98.PubMedCrossRef
4.
5.
Baracos VE. Hypercatabolism and hypermetabolism in wasting states. Curr Opin Clin Nutr Metab Care. 2002;5:237–9.PubMedCrossRef
6.
Gordon JN, Green SR, Goggin PM. Cancer cachexia. Q J Med. 2005;98:779–88.CrossRef
7.
Coats AJS. Treatment goals. In: Hofbauer KG, Anker SD, Inui A, Nicholson JR, editors. Pharmacotherapy of cachexia. Boca Raton, FL: CRC Press; 2006. p. 261–6.
8.
9.
Inui A. Cancer anorexia-cachexia syndrome: current issues in research and management. CA Cancer J Clin. 2002;52:72–91.PubMedCrossRef
10.
Winkler MF. Body composition changes in cancer cachexia: are they reversible? Top Clin Nutr. 2004;19:85–94.
11.
Mantovani G, Maccios A, Massa E, Madeddu C. Managing cancer-related anorexia/cachexia. Drugs. 2001;61:499–514.PubMedCrossRef
12.
Cahill GF, Aoki EE, Brennan MF, Muller WA. Insulin and muscle amino acid balance. Proc Nutr Soc. 1972;31:233–8.PubMedCrossRef
13.
Louard RJ, Fryburg DA, Gelfand RA, Barrett EJ. Insulin sensitivity of protein and glucose metabolism in human forearm skeletal muscle. J Clin Invest. 1992;90:2348–54.PubMedCrossRef
14.
Gelfand RA, Barrett EJ. Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. J Clin Invest. 1987;80:1–6.PubMedCrossRef
15.
Biolo G, Wolfe RR. Insulin action on protein metabolism. Baillieres Clin Endocrinol Metab. 1993;7:989–1005.PubMedCrossRef
16.
Wing SS, The UPS. In diabetes and obesity. BMC Biochem. 2003;9:56.
17.
Wang A, Hu Z, Hu J, Du J, Mitch WE. Insulin resistance accelerates muscle protein degradation: activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinol. 2006;147:4160–8.CrossRef
18.
Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, Phillips LS. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent ubiquitin-proteasome proteolytic pathway by a mechanism involving gene transcription. J Clin Invest. 1996;98:1703–8.PubMedCrossRef
19.
Mitch WE, Bailey JL, Wang X, Jurkovitz C, Newby D, Price SR. Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. Am J Physiol Cell Physiol. 1999;276:C1132–8.
20.
Hu J, Klein JD, Du J, Wang XH. Cardiac muscle protein catabolism in diabetes mellitus: activation of the ubiquitin-proteasome system by insulin deficiency. Endocrinol. 2008;149:5384–90.CrossRef
21.
Kino T, Mirani M, Alesci S, Chrousos GP. AIDS-related lipodystrophy/insulin resistance syndrome. Horm Metab Res. 2003;35:129–36.PubMedCrossRef
22.
Coats AJS, Anker S. Insulin resistance in chronic heart failure. J Cardiovasc Pharmacol. 2000;35:S9–S14.PubMedCrossRef
23.
Lecker SH, Solomon V, Mitch WE, Goldberg AL. Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. J Nutr. 1999;129:227S–37S.PubMed
24.
Lecker SH, Goldberg AL, Mitch WE. Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J Am Soc Nephrol. 2006;17:1807–19.PubMedCrossRef
25.
Rohdenburg GL, Bernard A, Krehbiel O. Sugar tolerance in cancer. JAMA. 1919;72:1528–30.CrossRef
26.
Glickman AS, Rawson RW. Diabetes and altered carbohydrate metabolism in patients with cancer. Cancer. 1956;9:1127–34.CrossRef
27.
Holroyde CP, Gabuzda TG, Putnam RC, Paul P, Reichard GA. Altered glucose metabolism in metastatic cancer. Cancer Res. 1975;35:3710–4.PubMed
28.
Jasani B, Donaldson LJ, Ratcliffe JG, Sokhi GS. Mechanism of impaired glucose tolerance in patients with neoplasia. Br J Cancer. 1978;38:287–92.PubMedCrossRef
29.
Lundholm K, Holm G, Schersten T. Insulin resistance in patients with cancer. Cancer Res. 1978;38:4665–70.PubMed
30.
Heber D, Chiebowski RT, Ishibashi DE, Herrold JN, Black JB. Abnormalities in glucose and protein metabolism in noncachectic lung cancer patients. Cancer Res. 1982;42:4815–9.PubMed
31.
Norton JA, Maher M, Wesley R, White D, Brennan MF. Glucose intolerance in sarcoma patients. Cancer. 1984;54:3022–7.PubMedCrossRef
32.
Tayek JA. A review of cancer cachexia and abnormal glucose metabolism in humans with cancer. J Am Coll Nutr. 1992;11:445–56.PubMed
33.
Yoshikawa T, Noguchi Y, Doi C, Makino T, Okamoto T, Matsumoto A. Insulin resistance was connected with the alterations of substrate utilization in patients with cancer. Cancer Lett. 1999;141:93–8.PubMedCrossRef
34.
Parekh N, Lin Y, Hayes RB, Albu JB, Lu-Yao GL. Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey. Cancer Cause Control. 2010;21:631–42.CrossRef
35.
Guaitani A, Recchia M, Carli M, Rocchetti M, Bartosek I, Garattini S. Walker carcinoma 256: a model for studies on tumor-induced anorexia and cachexia. Oncol. 1982;39:173–8.CrossRef
36.
Fernandes LC, Machado UF, Nogueira CR, Carpinelli AR, Curi R. Insulin secretion in Walker 256 tumor cachexia. Am J Physiol Endocrinol Metab. 1990;258:E1033–6.
37.
el Razi Neto SER, Zorn TMT, Curi R, Carpinelli AR. Impairment of insulin secretion in pancreatic islets isolated from Walker 256 tumor-bearing rats. Am J Physiol Cell Physiol. 1996;271:C804–9.
38.
Tanaka Y, Eda H, Tanaka T, Udagawa T, Ishikawa T, Horii I, Ishitsuka H, Kataoka T, et al. Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice. Cancer Res. 1990;50:2290–5.PubMed
39.
Asp ML, Tian M, Wendel AA, Belury MA. Evidence for the contribution of insulin resistance to the development of cachexia in tumor-bearing mice. Int J Cancer. 2009;126:756–63.CrossRef
40.
Lazarus DD, Destree AT, Mazzola LM, McCormack TA, Dick LR, Xu B, Huang JQ, Pierce JW, et al. A new model of cancer cachexia: contribution of the ubiquitin-proteasome pathway. Am J Physiol Endocrinol Metab. 1999;277:E332–41.
41.
Lundholm K, Korner U, Gunnebo L, Sixt-Ammilon P, Pouladiun M, Daneryd P, Bosaeus I. Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning. Clin Cancer Res. 2007;13:2699–706.PubMedCrossRef
42.
Fernandes LC, Carpinelli AR, Hell NS, Curi R. Improvement of cancer cachexia and decrease of Walker 256 tumor growth by insulin administration in rats. Cancer Ther Control. 1991;1:259–68.
43.
Fernandes LC, Curi R. Reversion of Walker 256 tumor cachexia by insulin treatment: possible mechanisms involved and perspectives for future research. Endocr Relat Cancer. 1997;4:465–74.CrossRef
44.
Piffar PM, Fernandez R, Tchaikovski O, Hirabara SM, Folador A, Pinto GJ, Jakobi S, Gobbo-Bordon D, et al. Naproxen, clenbuterol, and insulin administration ameliorates cancer cachexia and reduce tumor growth in Walker 256 tumor-bearing rats. Cancer Lett. 2003;201:139–48.PubMedCrossRef
45.
Moley JF, Morrison SD, Norton JA. Insulin reversal of cancer cachexia in rats. Cancer Res. 1985;45:4925–31.PubMed
46.
Moley JF, Morrison SD, Gorschboth CM, Norton JA. Body composition changes in rats with experimental cancer cachexia: improvement with exogenous insulin. Cancer Res. 1988;48:2784–7.PubMed
47.
Lazarus DD, Kambayashi T, Lowry SF, Strassmann G. The lack of an effect by insulin or insulin-like growth factor-1 in attenuating colon-26 mediated cancer cachexia. Cancer Lett. 1996;103:71–7.PubMedCrossRef
48.
Komer R, Vrana A. Thiazolidinediones: tools for the research of metabolic syndrome X. Physiol Res. 1998;47:215–25.
49.
Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Willimason JM, et al. Metformin increased AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002;51:2074–81.PubMedCrossRef
50.
Diamanti-Kandarakis E, Christakou CD, Kandaraki E, Economou FN. Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome. Eu J Endocrinol. 2010;162:193–212.CrossRef
51.
Wong AKF, al Zadjali MA, Choy AJ, Lang CC. Insulin resistance: a potential new target for therapy in patients with heart failure. Cardiovasc Ther. 2008;26:203–13.PubMedCrossRef
52.
Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007;100:328–41.PubMedCrossRef
53.
Diamanti-Kandarakis E, Economou F, Palimeri S, Christakou C. Metformin in polycystic ovary syndrome. Ann N Y Acad Sci. 2010;1205:192–8.PubMedCrossRef
54.
55.
Miyazaki Y, He H, Mandarino LJ, DeFronzo RA. Rosiglitazone improves downstream insulin receptor signaling in type 2 diabetic patients. Diabetes. 2003;52:1943–50.PubMedCrossRef
56.
Kintscher U, Law RE. PPARγ-mediated insulin sensitization: the importance of fat versus muscle. Am J Physiol Endocrinol Metab. 2005;288:E287–91.PubMedCrossRef
57.
Gagnon B, Bruera E. A review of the drug treatment of cachexia associated with cancer. Drugs. 1998;55:675–88.PubMedCrossRef
58.
Lambert CP, Uc EY, Evans WJ. β2-adrenergic agonists in the treatment of muscle atrophy. In: Hofbauer KG, Anker SD, Inui A, Nicholson JR, editors. Pharmacotherapy of cachexia. Boca Raton, FL: CRC Press; 2006. p. 3311–24.
59.
Castle A, Yaspelkis BB, Kuo C, Ivy JL. Attenuation of insulin resistance by chronic β2-adrenergic agonist treatment: possible muscle specific contributions. Life Sci. 2001;69:599–611.PubMedCrossRef
60.
Busquet S, Figueras MT, Fuster G, Almendro V, Moore-Carraso R, Ametller E, Argiles JM, Lopez-Soriano FJ. Anticachectic effects of formoterol: a drug for potential treatment of muscle wasting. Cancer Res. 2004;64:6725–31.CrossRef
61.
Nevzorova J, Evans BA, Bengtsson T, Summers RJ. Multiple signaling pathways involved in β2-adrenoceptor-mediated glucose uptake in rat skeletal muscle cells. Br J Pharmacol. 2006;147:446–54.PubMedCrossRef
62.
Matthael S, Stumvoli M, Kellerer M, Haring H. Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev. 2000;21:585–618.CrossRef
63.
von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle. J Cachex Sarcopenia Muscle. 2010;1:7–8.CrossRef
Metadata
Title
The role of insulin resistance in the development of muscle wasting during cancer cachexia
Authors
Mary A. Honors
Kimberly P. Kinzig
Publication date
01-03-2012
Publisher
Springer-Verlag
Published in
Journal of Cachexia, Sarcopenia and Muscle / Issue 1/2012
Print ISSN: 2190-5991
Electronic ISSN: 2190-6009
DOI
https://doi.org/10.1007/s13539-011-0051-5

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