Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony.

Recent data underscore the importance of intertissue communication in the maintenance of normal glucose homeostasis. Important signals are conveyed by hormones, cytokines, and fuel substrates and are sensed through a variety of cellular mechanisms. The ability of tissues to sense and adapt to changes in metabolic status and fuel availability is altered in insulin-resistant states including type 2 diabetes. Here we review the roles of glucose and its metabolites as signaling molecules and the diverse physiologic mechanisms for glucose sensing.

[1]  P. Felig.  The glucose-alanine cycle. , 1973, Metabolism: clinical and experimental.

[2]  M. Prentki,et al.  Metabolic Fate of Glucose in Purified Islet Cells , 1997, The Journal of Biological Chemistry.

[3]  M. Birnbaum,et al.  AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus , 2004, Nature.

[4]  K-U. Lee,et al.  Hypothalamic AMP-activated protein kinase mediates counter-regulatory responses to hypoglycaemia in rats , 2005, Diabetologia.

[5]  A. Mokdad,et al.  Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. , 2003, JAMA.

[6]  Rena R Wing,et al.  Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. , 1999, American journal of physiology. Endocrinology and metabolism.

[7]  A. Pocai,et al.  Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism , 2005, Science.

[8]  Jochen Roeper,et al.  ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis , 2001, Nature Neuroscience.

[9]  J. Flier,et al.  Regulation of glucose transporter-specific mRNA levels in rat adipose cells with fasting and refeeding. Implications for in vivo control of glucose transporter number. , 1989, The Journal of clinical investigation.

[10]  R. DeFronzo.  PATHOGENESIS OF TYPE 2 DIABETES: METABOLIC AND MOLECULAR IMPLICATIONS FOR IDENTIFYING DIABETES GENES , 1997 .

[11]  F. Natt,et al.  Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D. McClain,et al.  Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance. , 1996, The Journal of clinical investigation.

[13]  J. Halaas,et al.  Leptin and the regulation of body weight in mammals , 1998, Nature.

[14]  R. Shulman,et al.  In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  G. Shulman,et al.  Effect of glucose, independent of changes in insulin and glucagon secretion, on alanine metabolism in the conscious dog. , 1980, The Journal of clinical investigation.

[16]  N. Barzilai,et al.  Mechanism by which hyperglycemia inhibits hepatic glucose production in conscious rats. Implications for the pathophysiology of fasting hyperglycemia in diabetes. , 1993, The Journal of clinical investigation.

[17]  M. Mueckler,et al.  Differential Effects of GLUT1 or GLUT4 Overexpression on Hexosamine Biosynthesis by Muscles of Transgenic Mice* , 1996, The Journal of Biological Chemistry.

[18]  S. Fujita,et al.  Celiac-superior mesenteric ganglionectomy, but not vagotomy, suppresses the sympathoadrenal response to insulin-induced hypoglycemia. , 2005, Diabetes.

[19]  R. Gougeon,et al.  Whole-body protein anabolic response is resistant to the action of insulin in obese women , 2005 .

[20]  P. O'Hara,et al.  Molecular cloning, cDNA sequence, and bacterial expression of human glutamine:fructose-6-phosphate amidotransferase. , 1992, The Journal of biological chemistry.

[21]  R. Bergman,et al.  Novel Glucosensor for Hypoglycemic Detection Localized to the Portal Vein , 1997, Diabetes.

[22]  R. Burcelin,et al.  Enhanced Insulin Action Due to Targeted GLUT4 Overexpression Exclusively in Muscle , 1996, Diabetes.

[23]  L. Rossetti,et al.  Type 2 diabetes — who is conducting the orchestra? , 1998, Nature Genetics.

[24]  L. Rossetti,et al.  Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. , 2003, The Journal of clinical investigation.

[25]  C. Mantzoros,et al.  Role of leptin in the neuroendocrine response to fasting , 1996, Nature.

[26]  J. García-Ruíz,et al.  Effect of short‐term exercise on the content of gluconeogenic metabolites in rat liver and kidney , 1979, FEBS letters.

[27]  T. Ono,et al.  Glucose and Osmosensitive Neurones of the Rat Hypothalamus , 1969, Nature.

[28]  D. Edgerton,et al.  Effect of vagal cooling on the counterregulatory response to hypoglycemia induced by a low dose of insulin in the conscious dog. , 2001, Diabetes.

[29]  D. Kelley,et al.  Metabolic flexibility , 2004, The Proceedings of the Nutrition Society.

[30]  H. Lodish,et al.  Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators. , 2002, American journal of physiology. Endocrinology and metabolism.

[31]  W. Soeller,et al.  Germline manipulation of glucose homeostasis via alteration of glucose transporter levels in skeletal muscle. , 1993, The Journal of biological chemistry.

[32]  N. Fujii,et al.  AMP-activated Protein Kinase α2 Activity Is Not Essential for Contraction- and Hyperosmolarity-induced Glucose Transport in Skeletal Muscle* , 2005, Journal of Biological Chemistry.

[33]  O. Wieland.  The mammalian pyruvate dehydrogenase complex: structure and regulation. , 1983, Reviews of physiology, biochemistry and pharmacology.

[34]  U. Smith,et al.  Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. , 2006, The New England journal of medicine.

[35]  M. J. MacDonald,et al.  Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion. , 2005, American journal of physiology. Endocrinology and metabolism.

[36]  J. McGarry,et al.  What if Minkowski had been ageusic? An alternative angle on diabetes. , 1992, Science.

[37]  D. Pipeleers,et al.  Glucose sensing in pancreatic beta-cells: a model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus. , 2001, Diabetes.

[38]  G. Alleyne,et al.  Renal Ammoniagenesis in Rats Made Acutely Acidotic by Swimming , 1984, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[39]  A. Jaeschke,et al.  Mammalian TOR: A Homeostatic ATP Sensor , 2001, Science.

[40]  C. Long,et al.  Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat. , 1983, The Biochemical journal.

[41]  R. McPherson,et al.  Transgenic mice expressing the human GLUT4/muscle-fat facilitative glucose transporter protein exhibit efficient glycemic control. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[42]  K. Kotani,et al.  Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle. , 2005, American journal of physiology. Endocrinology and metabolism.

[43]  D. Hardie,et al.  AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. , 2005, Cell metabolism.

[44]  P. Cryer,et al.  Hypoglycemia in diabetes. , 2003, Diabetes care.

[45]  G. Shulman,et al.  Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver , 2001, Nature.

[46]  J. Flier,et al.  Adipose Tissue as an Endocrine Organ , 2014 .

[47]  Demetrios Vavvas,et al.  Malonyl-CoA, fuel sensing, and insulin resistance. , 1999, American journal of physiology. Endocrinology and metabolism.

[48]  R. T. Hoffman,et al.  Overexpression of glutamine: fructose-6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance. , 2000, Diabetes.

[49]  Nimesh Mody,et al.  Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes , 2005, Nature.

[50]  Y. Deshaies,et al.  Regulation of leptin secretion from white adipocytes by insulin, glycolytic substrates, and amino acids. , 2005, American journal of physiology. Endocrinology and metabolism.

[51]  S. Uchida,et al.  Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase , 2002, Nature Medicine.

[52]  M. Lazar,et al.  The hormone resistin links obesity to diabetes , 2001, Nature.

[53]  M. Salminen,et al.  Improvement of Insulin Action in Diabetic Transgenic Mice Selectively Overexpressing GLUT4 in Skeletal Muscle , 1996, Diabetes.

[54]  Young-Bum Kim,et al.  Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase , 2002, Nature.

[55]  C. Chapron,et al.  Rosiglitazone Controls Fatty Acid Cycling in Human Adipose Tissue by Means of Glyceroneogenesis and Glycerol Phosphorylation* , 2006, Journal of Biological Chemistry.

[56]  B. Kahn,et al.  Transgenic GLUT-4 overexpression in fat enhances glucose metabolism: preferential effect on fatty acid synthesis. , 1995, The American journal of physiology.

[57]  C. Warden,et al.  Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. , 1998, Endocrinology.

[58]  P. J. Randle.  Fuel selection in animals. , 1986, Biochemical Society transactions.

[59]  B. Glaser,et al.  Pancreatic beta-cell glucokinase: closing the gap between theoretical concepts and experimental realities. , 1998, Diabetes.

[60]  C. Kahn,et al.  Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. , 2001, The Journal of clinical investigation.

[61]  L. Rossetti,et al.  Molecular disruption of hypothalamic nutrient sensing induces obesity , 2006, Nature Neuroscience.

[62]  K. M. Popov,et al.  Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. , 1998, The Biochemical journal.

[63]  B. Witherbee,et al.  Activation of the hexosamine signaling pathway in adipose tissue results in decreased serum adiponectin and skeletal muscle insulin resistance. , 2004, Endocrinology.

[64]  J. Katz,et al.  Gluconeogenesis and the Cori cycle in 12-, 20-, and 40-h-fasted humans. , 1998, American journal of physiology. Endocrinology and metabolism.

[65]  B. Wadzinski,et al.  Xylulose 5-phosphate mediates glucose-induced lipogenesis by xylulose 5-phosphate-activated protein phosphatase in rat liver , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[66]  F. Sistare,et al.  The interaction between the cytosolic pyridine nucleotide redox potential and gluconeogenesis from lactate/pyruvate in isolated rat hepatocytes. Implications for investigations of hormone action. , 1985, The Journal of biological chemistry.

[67]  G. Shulman,et al.  Glucose disposal during insulinopenia in somatostatin-treated dogs. The roles of glucose and glucagon. , 1978, The Journal of clinical investigation.

[68]  D. Hardie,et al.  AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. , 1997, American journal of physiology. Endocrinology and metabolism.

[69]  G. Taborsky,et al.  The contribution of the autonomic nervous system to changes of glucagon and insulin secretion during hypoglycemic stress. , 1989, Endocrine reviews.

[70]  Wilhelm Haas,et al.  Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1 , 2005, Nature.

[71]  K. M. Popov,et al.  Isoenzymes of Pyruvate Dehydrogenase Phosphatase , 1998, The Journal of Biological Chemistry.

[72]  R. Hanson,et al.  A possible physiological role for glyceroneogenesis in rat adipose tissue. , 1970, The Journal of biological chemistry.

[73]  D. Wasserman.  Regulation of glucose fluxes during exercise in the postabsorptive state. , 1995, Annual review of physiology.

[74]  J. McGarry,et al.  A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. , 1977, The Journal of clinical investigation.

[75]  M. Mueckler,et al.  Differential effects of GLUT-1 or GLUT-4 overexpression on insulin responsiveness in transgenic mice. , 1994, The American journal of physiology.

[76]  M. Stumvoll,et al.  Estimation of glucose-alanine-lactate-glutamine cycles in postabsorptive humans: role of skeletal muscle. , 1995, The American journal of physiology.

[77]  R. Burcelin,et al.  Portal glucose infusion in the mouse induces hypoglycemia: evidence that the hepatoportal glucose sensor stimulates glucose utilization. , 2000, Diabetes.

[78]  R. Henry,et al.  Glutamine:fructose-6-phosphate amidotransferase activity in cultured human skeletal muscle cells: relationship to glucose disposal rate in control and non-insulin-dependent diabetes mellitus subjects and regulation by glucose and insulin. , 1996, The Journal of clinical investigation.

[79]  B. Kahn,et al.  Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus. , 1999, The New England journal of medicine.

[80]  M. Sakurai,et al.  A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[81]  A. Cherrington,et al.  Autoregulation of hepatic glucose production. , 1998, European journal of endocrinology.

[82]  S. Kalhan,et al.  The Key Role of Anaplerosis and Cataplerosis for Citric Acid Cycle Function* , 2002, The Journal of Biological Chemistry.

[83]  M. Prentki,et al.  A Role for Hypothalamic Malonyl-CoA in the Control of Food Intake* , 2005, Journal of Biological Chemistry.

[84]  Y. Terauchi,et al.  The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity , 2001, Nature Medicine.

[85]  L. Pénicaud,et al.  A new ATP-sensitive K+ channel-independent mechanism is involved in glucose-excited neurons of mouse arcuate nucleus. , 2004, Diabetes.

[86]  D. James,et al.  Dose-response curves for in vivo insulin sensitivity in individual tissues in rats. , 1985, The American journal of physiology.

[87]  C. Kahn,et al.  Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance , 2000, Nature Medicine.

[88]  K. M. Popov,et al.  Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart. , 1998, The Biochemical journal.

[89]  S. Turner,et al.  Physiologic and Pharmacologic Factors Influencing Glyceroneogenic Contribution to Triacylglyceride Glycerol Measured by Mass Isotopomer Distribution Analysis* , 2005, Journal of Biological Chemistry.