Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression

JCI Insight
James T ThackerayDenise Hilfiker-Kleiner

Abstract

Advanced cancer induces fundamental changes in metabolism and promotes cardiac atrophy and heart failure. We discovered systemic insulin deficiency in cachectic cancer patients. Similarly, mice with advanced B16F10 melanoma (B16F10-TM) or colon 26 carcinoma (C26-TM) displayed decreased systemic insulin associated with marked cardiac atrophy, metabolic impairment, and function. B16F10 and C26 tumors decrease systemic insulin via high glucose consumption, lowering pancreatic insulin production and producing insulin-degrading enzyme. As tumor cells consume glucose in an insulin-independent manner, they shift glucose away from cardiomyocytes. Since cardiomyocytes in both tumor models remained insulin responsive, low-dose insulin supplementation by subcutaneous implantation of insulin-releasing pellets improved cardiac glucose uptake, atrophy, and function, with no adverse side effects. In addition, by redirecting glucose to the heart in addition to other organs, the systemic insulin treatment lowered glucose usage by the tumor and thereby decreased tumor growth and volume. Insulin corrected the cancer-induced reduction in cardiac Akt activation and the subsequent overactivation of the proteasome and autophagy. Thus, cancer-induced ...Continue Reading

References

Dec 6, 2000·European Journal of Nuclear Medicine·F M BengelM Schwaiger
Apr 26, 2005·BMJ : British Medical Journal·Josie M M EvansAndrew D Morris
Aug 1, 1997·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·I De BlaauwM F Von Meyenfeldt
Jul 18, 2006·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·I De BlaauwM F Von Meyenfeldt
Feb 10, 2007·Cell·Denise Hilfiker-KleinerHelmut Drexler
May 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kent LundholmIngvar Bosaeus
Mar 28, 2008·The New England Journal of Medicine·Joseph A Hill, Eric N Olson
May 12, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Tamás RadovitsGábor Szabó
Feb 8, 2011·The Lancet Oncology·Kenneth FearonVickie E Baracos
Apr 9, 2011·Journal of Cachexia, Sarcopenia and Muscle·Stephan von Haehling, Stefan D Anker
Mar 28, 2012·Journal of Cachexia, Sarcopenia and Muscle·Mary A Honors, Kimberly P Kinzig
Dec 5, 2012·Endocrine-related Cancer·Sefirin DjioguePaul Faustin Seke Etet
Mar 19, 2013·Trends in Molecular Medicine·Suman K Das, Gerald Hoefler
Apr 27, 2013·The Journal of Clinical Investigation·Julie HalkeinIngrid Struman
Aug 31, 2013·European Heart Journal·Jochen SpringerStefan D Anker
Oct 5, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Andrew M HernandezGrant T Gullberg
Feb 12, 2014·Journal of Molecular and Cellular Cardiology·Changhan OuyangZhonglin Xie
Feb 25, 2014·Vitamins and Hormones·Marcia HiriartCarlos Manlio Diaz-Garcia
Nov 13, 2014·European Journal of Nuclear Medicine and Molecular Imaging·James T ThackerayFrank M Bengel
Jul 2, 2015·Metabolism: Clinical and Experimental·Kazuhiro NakataniShizuya Yamashita
Aug 15, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·James T ThackerayFrank M Bengel
Jan 1, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Kate T Murphy
Apr 2, 2016·Circulation Research·Christian Riehle, E Dale Abel

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Citations

Jul 7, 2019·ESC Heart Failure·Markus B HeckmannLorenz H Lehmann
Jun 28, 2019·Cardiovascular Research·Christian Riehle, Johann Bauersachs
Jul 7, 2019·The Journal of Physiology·Mara BrancaccioAlessandra Ghigo
Feb 8, 2019·Aging·Valentina SalaAlessandra Ghigo
Jun 17, 2020·Herz·Tobias J PfefferDenise Hilfiker-Kleiner
Aug 3, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Stefan PietzschDenise Hilfiker-Kleiner
Feb 7, 2021·Current Treatment Options in Oncology·Michele RussoAlessandra Ghigo
Jun 25, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Mingchuan LiAlessandra Ghigo
Mar 10, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·James T Thackeray
Aug 3, 2021·Biochemical Society Transactions·Ana Sayuri Yamagata, Paula Paccielli Freire
Aug 28, 2021·Antioxidants·Priyanka KarekarShubha Gururaja Rao
Aug 28, 2021·Life·Julia Windi GunadiRonny Lesmana
Aug 31, 2021·European Heart Journal·Gilda VarricchiCarlo G Tocchetti

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Methods Mentioned

BETA
ELISA
FCS
PCR

Software Mentioned

Living Image
Image Lab
VisualSonics
Visual Sonics Vevo 770

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