Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer.
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.
Marshall
Stephen
S
Hexos Inc., 18304 NE 153rd Street, Woodinville, WA 98072, USA. hexos06@comcast.net
D000091162:AMP-Activated Protein Kinase Kinases; D052242:Adiponectin / Q000502:physiology; D000596:Amino Acids / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000502:physiology; D020738:Leptin / Q000502:physiology; D008660:Metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology; D009765:Obesity / Q000188:drug therapy / Q000209:etiology; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D052242:Adiponectin; D000596:Amino Acids; D006595:Hexosamines; D007328:Insulin; D020738:Leptin; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D005947:Glucose