Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 1 August 2006
Vol. 2006, Issue 346, p. re7
[DOI: 10.1126/stke.3462006re7]

REVIEWS

Role of Insulin, Adipocyte Hormones, and Nutrient-Sensing Pathways in Regulating Fuel Metabolism and Energy Homeostasis: A Nutritional Perspective of Diabetes, Obesity, and Cancer

Stephen Marshall*

Hexos Inc., 18304 NE 153rd Street, Woodinville, WA 98072, USA.

Abstract: Traditionally, nutrients such as glucose and amino acids have been viewed as substrates for the generation of high-energy molecules and as precursors for the biosynthesis of macromolecules. However, it is now apparent that nutrients also function as signaling molecules in functionally diverse signal transduction pathways. Glucose and amino acids trigger signaling cascades that regulate various aspects of fuel and energy metabolism and control the growth, proliferation, and survival of cells. Here, we provide a functional and regulatory overview of three well-established nutrient signaling pathways—the hexosamine signaling pathway, the mTOR (mammalian target of rapamycin) signaling pathway, and the adenosine monophosphate–activated protein kinase (AMPK) signaling pathway. Nutrient signaling pathways are interconnected, coupled to insulin signaling, and linked to the release of metabolic hormones from adipose tissue. Thus, nutrient signaling pathways do not function in isolation. Rather, they appear to serve as components of a larger "metabolic regulatory network" that controls fuel and energy metabolism (at the cell, tissue, and whole-body levels) and links nutrient availability with cell growth and proliferation. Understanding the diverse roles of nutrients and delineating nutrient signaling pathways should facilitate drug discovery research and the search for novel therapeutic compounds to prevent and treat various human diseases such as diabetes, obesity, and cancer.

*Corresponding author. E-mail, hexos06{at}comcast.net

Citation: S. Marshall, Role of Insulin, Adipocyte Hormones, and Nutrient-Sensing Pathways in Regulating Fuel Metabolism and Energy Homeostasis: A Nutritional Perspective of Diabetes, Obesity, and Cancer. Sci. STKE 2006, re7 (2006).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
TRIB3 Mediates Glucose-Induced Insulin Resistance via a Mechanism That Requires the Hexosamine Biosynthetic Pathway.
W. Zhang, J. Liu, L. Tian, Q. Liu, Y. Fu, and W. T. Garvey (2013)
Diabetes 62, 4192-4200
   Abstract »    Full Text »    PDF »
Cranberry Interacts With Dietary Macronutrients to Promote Healthy Aging in Drosophila.
C. Wang, J. Yolitz, T. Alberico, M. Laslo, Y. Sun, C. T. Wheeler, X. Sun, and S. Zou (2013)
J Gerontol A Biol Sci Med Sci
   Abstract »    Full Text »    PDF »
Altered lipid homeostasis in Drosophila InsP3 receptor mutants leads to obesity and hyperphagia.
M. Subramanian, S. K. Metya, S. Sadaf, S. Kumar, D. Schwudke, and G. Hasan (2013)
Dis. Model. Mech. 6, 734-744
   Abstract »    Full Text »    PDF »
Fat Body dSir2 Regulates Muscle Mitochondrial Physiology and Energy Homeostasis Nonautonomously and Mimics the Autonomous Functions of dSir2 in Muscles.
K. K. Banerjee, C. Ayyub, S. Sengupta, and U. Kolthur-Seetharam (2013)
Mol. Cell. Biol. 33, 252-264
   Abstract »    Full Text »    PDF »
Critical Role of O-Linked {beta}-N-Acetylglucosamine Transferase in Prostate Cancer Invasion, Angiogenesis, and Metastasis.
T. P. Lynch, C. M. Ferrer, S. R. Jackson, K. S. Shahriari, K. Vosseller, and M. J. Reginato (2012)
J. Biol. Chem. 287, 11070-11081
   Abstract »    Full Text »    PDF »
Cell signaling pathways associated with a reduction in mammary cancer burden by dietary common bean (Phaseolus vulgaris L.).
M. D. Thompson, M. M. Mensack, W. Jiang, Z. Zhu, M. R. Lewis, J. N. McGinley, M. A. Brick, and H. J. Thompson (2012)
Carcinogenesis 33, 226-232
   Abstract »    Full Text »    PDF »
A lipid-droplet-targeted O-GlcNAcase isoform is a key regulator of the proteasome.
C. N. Keembiyehetty, A. Krzeslak, D. C. Love, and J. A. Hanover (2011)
J. Cell Sci. 124, 2851-2860
   Abstract »    Full Text »    PDF »
Structural Bases of PAS Domain-regulated Kinase (PASK) Activation in the Absence of Activation Loop Phosphorylation.
C. K. Kikani, S. A. Antonysamy, J. B. Bonanno, R. Romero, F. F. Zhang, M. Russell, T. Gheyi, M. Iizuka, S. Emtage, J. M. Sauder, et al. (2010)
J. Biol. Chem. 285, 41034-41043
   Abstract »    Full Text »    PDF »
Parenteral Amino Acid Intakes in Critically Ill Children: A Matter of Convenience.
S. Verbruggen, J. Sy, A. Arrivillaga, K. Joosten, J. van Goudoever, and L. Castillo (2010)
JPEN J Parenter Enteral Nutr 34, 329-340
   Abstract »    Full Text »    PDF »
Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity.
D. C. Love, S. Ghosh, M. A. Mondoux, T. Fukushige, P. Wang, M. A. Wilson, W. B. Iser, C. A. Wolkow, M. W. Krause, and J. A. Hanover (2010)
PNAS 107, 7413-7418
   Abstract »    Full Text »    PDF »
Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance.
J. Liu, X. Wu, J. L. Franklin, J. L. Messina, H. S. Hill, D. R. Moellering, R. G. Walton, M. Martin, and W. T. Garvey (2010)
Am J Physiol Endocrinol Metab 298, E565-E576
   Abstract »    Full Text »    PDF »
Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5'-aminoimidazole-4-carboxamide-1-{beta}-D-ribofuranoside.
D. A Rivas, B. B Yaspelkis III, J. A Hawley, and S. J Lessard (2009)
J. Endocrinol. 202, 441-451
   Abstract »    Full Text »    PDF »
Mechanism and Management of AKT Inhibitor-Induced Hyperglycemia.
M.-C. Crouthamel, J. A. Kahana, S. Korenchuk, S.-Y. Zhang, G. Sundaresan, D. J. Eberwein, K. K. Brown, and R. Kumar (2009)
Clin. Cancer Res. 15, 217-225
   Abstract »    Full Text »    PDF »
ATP Citrate Lyase: Activation and Therapeutic Implications in Non-Small Cell Lung Cancer.
T. Migita, T. Narita, K. Nomura, E. Miyagi, F. Inazuka, M. Matsuura, M. Ushijima, T. Mashima, H. Seimiya, Y. Satoh, et al. (2008)
Cancer Res. 68, 8547-8554
   Abstract »    Full Text »    PDF »
Neural Systems Controlling the Drive to Eat: Mind Versus Metabolism.
H. Zheng and H.-R. Berthoud (2008)
Physiology 23, 75-83
   Abstract »    Full Text »    PDF »
SIGNAL TRANSDUCTION: Sweet Conundrum.
M. J. Birnbaum (2008)
Science 319, 1348-1349
   Abstract »    Full Text »    PDF »
Hepatic Glucose Sensing via the CREB Coactivator CRTC2.
R. Dentin, S. Hedrick, J. Xie, J. Yates III, and M. Montminy (2008)
Science 319, 1402-1405
   Abstract »    Full Text »    PDF »
PAS kinase is required for normal cellular energy balance.
H.-X. Hao, C. M. Cardon, W. Swiatek, R. C. Cooksey, T. L. Smith, J. Wilde, S. Boudina, E. D. Abel, D. A. McClain, and J. Rutter (2007)
PNAS 104, 15466-15471
   Abstract »    Full Text »    PDF »
Proteomics Analysis of Insulin Secretory Granules.
Y. Brunner, Y. Coute, M. Iezzi, M. Foti, M. Fukuda, D. F. Hochstrasser, C. B. Wollheim, and J.-C. Sanchez (2007)
Mol. Cell. Proteomics 6, 1007-1017
   Abstract »    Full Text »    PDF »
Non-human primate fetal kidney transcriptome analysis indicates mammalian target of rapamycin (mTOR) is a central nutrient-responsive pathway.
M. J. Nijland, N. E. Schlabritz-Loutsevitch, G. B. Hubbard, P. W. Nathanielsz, and L. A. Cox (2007)
J. Physiol. 579, 643-656
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882