- Understanding the Warburg effect: the metabolic requirements of cell proliferation
Matthew G Vander Heiden
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Science 324:1029-33. 2009
..A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer...
- Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes
Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA
Science 306:457-61. 2004
..Pharmacologic manipulation of this pathway may offer novel opportunities for treating these common diseases...
- PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
Vamsi K Mootha
Whitehead Institute MIT Center for Genome Research, Cambridge, Massachusetts, USA
Nat Genet 34:267-73. 2003
..Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity...
- Insulin signalling and the regulation of glucose and lipid metabolism
A R Saltiel
Life Sciences Institute, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
Nature 414:799-806. 2001
The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin...
- TLR4 links innate immunity and fatty acid-induced insulin resistance
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 116:3015-25. 2006
..lipid infusion to (a) suppress insulin signaling in muscle and (b) reduce insulin-mediated changes in systemic glucose metabolism...
- Role of AMP-activated protein kinase in mechanism of metformin action
Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
J Clin Invest 108:1167-74. 2001
Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization...
- Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes
Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA
Science 313:1137-40. 2006
..Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes...
- MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity
Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
J Clin Invest 116:1494-505. 2006
..These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice...
- The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes
Arnold J Levine
Institute for Advanced Study, Princeton, NJ 08540, USA
Science 330:1340-4. 2010
..Tumor cells take up much more glucose and mainly process it through aerobic glycolysis, producing large quantities of secreted lactate with a lower use ..
- TSC2 mediates cellular energy response to control cell growth and survival
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Cell 115:577-90. 2003
..These observations demonstrate a model where TSC2 functions as a key player in regulation of the common mTOR pathway of protein synthesis, cell growth, and viability in response to cellular energy levels...
- Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance
Justin I Odegaard
Division of Endocrinology, Metabolism and Gerontology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305 5103, USA
Nature 447:1116-20. 2007
..activation, and predisposes these animals to development of diet-induced obesity, insulin resistance, and glucose intolerance...
- The Lin28/let-7 axis regulates glucose metabolism
Stem Cell Transplantation Program, Division of Pediatric Hematology Oncology, Children s Hospital Boston and Dana Farber Cancer Institute, Boston, MA, USA
Cell 147:81-94. 2011
..Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance...
- Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans
Kimber L Stanhope
Department of Molecular Biosciences, UCD, Davis, California 95616, USA
J Clin Invest 119:1322-34. 2009
Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance...
- Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state
Institut Cochin, Universite Paris Descartes, CNRS UMR 8104, Paris, France
J Clin Invest 120:2355-69. 2010
..Surprisingly, here we have found that in mice lacking AMPK in the liver, blood glucose levels were comparable to those in wild-type mice, and the hypoglycemic effect of metformin was maintained...
- The effects of alternate optimal solutions in constraint-based genome-scale metabolic models
Genomatica, Inc, Bioprocessing Division, 5405 Morehouse Drive, Suite 210, San Diego, CA 92121, USA
Metab Eng 5:264-76. 2003
..Sample results are provided for growth predictions of E. coli using glucose, acetate, and lactate as carbon substrates...
- Mitochondrial dysfunction and type 2 diabetes
Bradford B Lowell
Department of Medicine, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Harvard Medical School, Boston, MA 02215, USA
Science 307:384-7. 2005
Maintenance of normal blood glucose levels depends on a complex interplay between the insulin responsiveness of skeletal muscle and liver and glucose-stimulated insulin secretion by pancreatic beta cells...
- The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin
Reuben J Shaw
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
Science 310:1642-6. 2005
..Adenoviral small hairpin RNA (shRNA) for TORC2 reduced PGC-1alpha expression and normalized blood glucose levels in mice with deleted liver LKB1, indicating that TORC2 is a critical target of LKB1/AMPK signals in the ..
- Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction
David R Wise
Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
Proc Natl Acad Sci U S A 105:18782-7. 2008
Mammalian cells fuel their growth and proliferation through the catabolism of two main substrates: glucose and glutamine...
- Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo
Novocell, Inc, 3550 General Atomics Ct, San Diego, California 92121, USA
Nat Biotechnol 26:443-52. 2008
..Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice...
- Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice
Unit of Pharmacology and Therapeutics, Universite Catholique de Louvain, Brussels, Belgium
J Clin Invest 118:3930-42. 2008
..Hypoxic tumor cells primarily use glucose for glycolytic energy production and release lactic acid, creating a lactate gradient that mirrors the oxygen ..
- Adipocytes as regulators of energy balance and glucose homeostasis
Evan D Rosen
Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Centre, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Nature 444:847-53. 2006
..Adipose tissue also serves as a crucial integrator of glucose homeostasis...
- HIF-1: upstream and downstream of cancer metabolism
Gregg L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, United States
Curr Opin Genet Dev 20:51-6. 2010
..HIF-1) plays a key role in the reprogramming of cancer metabolism by activating transcription of genes encoding glucose transporters and glycolytic enzymes, which take up glucose and convert it to lactate; pyruvate dehydrogenase ..
- Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1
Joseph T Rodgers
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 434:113-8. 2005
Homeostatic mechanisms in mammals respond to hormones and nutrients to maintain blood glucose levels within a narrow range...
- Crystal structure of a bacterial homologue of glucose transporters GLUT1-4
State Key Laboratory of Bio membrane and Membrane Biotechnology, Center for Structural Biology, Tsinghua University, Beijing 100084, China
Nature 490:361-6. 2012
b>Glucose transporters are essential for metabolism of glucose in cells of diverse organisms from microbes to humans, exemplified by the disease-related human proteins GLUT1, 2, 3 and 4...
- Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA
Cell Metab 8:301-9. 2008
..Together, these results indicate that these CD11c+ cells are a potential therapeutic target for treatment of obesity-related insulin resistance and type II diabetes...
- AMP-activated protein kinase induces a p53-dependent metabolic checkpoint
Russell G Jones
Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Mol Cell 18:283-93. 2005
..Here we show that proliferating mammalian cells have a cell-cycle checkpoint that responds to glucose availability...
- Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis
Ralph J DeBerardinis
Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Room 450, BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104 6160, USA
Proc Natl Acad Sci U S A 104:19345-50. 2007
..Many tumor cells exhibit rapid glucose consumption, with most of the glucose-derived carbon being secreted as lactate despite abundant oxygen ..
- The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism
Seung Hoi Koo
Peptide Biology Laboratories, Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, California 92037 1002, USA
Nature 437:1109-11. 2005
b>Glucose homeostasis is regulated systemically by hormones such as insulin and glucagon, and at the cellular level by energy status...
- ATP-citrate lyase links cellular metabolism to histone acetylation
Kathryn E Wellen
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Science 324:1076-80. 2009
..Metazoans, however, use glucose as their main carbon source and have exposure only to low concentrations of extracellular acetate...
- Akt stimulates aerobic glycolysis in cancer cells
Rebecca L Elstrom
Department of Cancer Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Cancer Res 64:3892-9. 2004
..However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation...
- Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis
Center for Autophagy Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
Nature 481:511-5. 2012
..BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-..
- Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming
Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2 1 Seiryo machi, Aoba ku, Sendai, Miyagi, 980 8575, Japan
Cancer Cell 22:66-79. 2012
..Here, we show that Nrf2 redirects glucose and glutamine into anabolic pathways, especially under the sustained activation of PI3K-Akt signaling...
- Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity
Division of Endocrinology and Metabolic Diseases, University of Verona Medical School, Italy
Diabetes Care 23:57-63. 2000
..To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin sensitivity in humans...
- Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function
K T Uysal
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
Nature 389:610-4. 1997
..These results indicate that TNF-alpha is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action...
- Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy
Tineke W H Meijer
Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Clin Cancer Res 18:5585-94. 2012
..studies and the first clinical phase I/II trials, it can be concluded that targeting HIF-1 and tumor glucose metabolism at several levels reduces the antioxidant capacity of tumors, affects the tumor microenvironment, and ..
- Lack of interleukin-1 receptor I (IL-1RI) protects mice from high-fat diet-induced adipose tissue inflammation coincident with improved glucose homeostasis
Fiona C McGillicuddy
Nutrigenomics Research Group, University College Dublin Conway Institute, School of Public Health and Population Science, University College Dublin, Dublin, Ireland
Diabetes 60:1688-98. 2011
..We hypothesized that lack of IL-1RI may ameliorate HFD-induced IR by attenuating adipose tissue inflammation...
- Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress
Tim J Schulz
Department of Human Nutrition, Institute of Nutrition, University of Jena, D 07743 Jena, Germany
Cell Metab 6:280-93. 2007
Increasing cellular glucose uptake is a fundamental concept in treatment of type 2 diabetes, whereas nutritive calorie restriction increases life expectancy...
- AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 428:569-74. 2004
..hypothalamus (PVH) by the anorexigenic hormone leptin, and in multiple hypothalamic regions by insulin, high glucose and refeeding...
- Translational control is required for the unfolded protein response and in vivo glucose homeostasis
Howard Hughes Medical Institute, University of Michigan Medical Center, 48109, Ann Arbor, MI, USA
Mol Cell 7:1165-76. 2001
..Subsequently, transcription of genes encoding adaptive functions including the glucose-regulated proteins is induced...
- Cancer's molecular sweet tooth and the Warburg effect
Jung whan Kim
Division of Hematology, Department of Medicine, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cancer Res 66:8927-30. 2006
More than 80 years ago, the renowned biochemist Otto Warburg described how cancer cells avidly consume glucose and produce lactic acid under aerobic conditions...
- Hypoxia, HIF1 and glucose metabolism in the solid tumour
Nicholas C Denko
Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, USA
Nat Rev Cancer 8:705-13. 2008
..As discussed in this Perspective, new data suggests that this metabolic switch may provide a benefit to the tumour not by increasing glycolysis but by decreasing mitochondrial activity...
- Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Nat Genet 42:142-8. 2010
b>Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes...
- Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance
Valeria R Fantin
Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
Cancer Cell 9:425-34. 2006
..These results demonstrate that LDH-A plays a key role in tumor maintenance...
- Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver
E D Abel
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 409:729-33. 2001
The earliest defect in developing type 2 diabetes is insulin resistance, characterized by decreased glucose transport and metabolism in muscle and adipocytes...
- Regulation of glucose transporter translocation in health and diabetes
Jonathan S Bogan
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
Annu Rev Biochem 81:507-32. 2012
To enhance glucose uptake into muscle and fat cells, insulin stimulates the translocation of GLUT4 glucose transporters from intracellular membranes to the cell surface...
- Lipid-induced insulin resistance: unravelling the mechanism
Varman T Samuel
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536 8012, USA
Lancet 375:2267-77. 2010
..More than 40 years ago, Randle and colleagues postulated that lipids impaired insulin-stimulated glucose use by muscles through inhibition of glycolysis at key points...
- A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information
Adam M Feist
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA
Mol Syst Biol 3:121. 2007
..The increased scope and computational capability using this new reconstruction is expected to broaden the spectrum of both basic biology and applied systems biology studies of E. coli metabolism...
- Regulation of glucose transport by insulin: traffic control of GLUT4
Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48105, USA
Nat Rev Mol Cell Biol 13:383-96. 2012
Despite daily fasting and feeding, plasma glucose levels are normally maintained within a narrow range owing to the hormones insulin and glucagon...
- Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets
Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland
J Clin Invest 110:851-60. 2002
..Recently, we have shown that increased glucose concentrations also induce Fas expression and beta cell apoptosis in human islets...
- Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells
Division of Gastrointestinal and Liver Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Cell Metab 15:110-21. 2012
..of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using stable isotope-resolved metabolomics...
- A pancreatic islet-specific microRNA regulates insulin secretion
Matthew N Poy
Laboratory of Metabolic Diseases and Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
Nature 432:226-30. 2004
..Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion...
- Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta)
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
Science 292:1728-31. 2001
b>Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver...
- Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 106:15430-5. 2009
..Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues...
- Toward homosuccinate fermentation: metabolic engineering of Corynebacterium glutamicum for anaerobic production of succinate from glucose and formate
Institut für Bio und Geowissenschaften, IBG 1 Biotechnologie, Forschungszentrum Julich, Julich, Germany
Appl Environ Microbiol 78:3325-37. 2012
..studies have demonstrated the capability of Corynebacterium glutamicum for anaerobic succinate production from glucose under nongrowing conditions...
- Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis
Institute for Research in Biomedicine IRB Barcelona, 08028 Barcelona, Spain
Proc Natl Acad Sci U S A 109:5523-8. 2012
..Liver-specific ablation of Mfn2 in mice led to numerous metabolic abnormalities, characterized by glucose intolerance and enhanced hepatic gluconeogenesis. Mfn2 deficiency impaired insulin signaling in liver and muscle...
- The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
A H Berg
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA
Nat Med 7:947-53. 2001
..Acrp30 leads to a 2-3-fold elevation in circulating Acrp30 levels, which triggers a transient decrease in basal glucose levels...
- How Saccharomyces responds to nutrients
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
Annu Rev Genet 42:27-81. 2008
- Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism
Sabine D Jordan
Department of Mouse Genetics and Metabolism, Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases CECAD, University of Cologne, University Hospital Cologne, Max Planck Institute for Neurological Research, Zulpicher Strasse 47, D 50674 Cologne, Germany
Nat Cell Biol 13:434-46. 2011
..Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis...
- Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
J Biol Chem 274:305-15. 1999
..GK only in the liver are only mildly hyperglycemic but display pronounced defects in both glycogen synthesis and glucose turnover rates during a hyperglycemic clamp...
- Crosstalk between components of circadian and metabolic cycles in mammals
Department of Molecular Biology and National Centre of Competence in Research Frontiers in Genetics, Sciences III, University of Geneva, 30, Quai Ernest Ansermet, CH 1211 Geneva 4, Switzerland
Cell Metab 13:125-37. 2011
..The intertwining between these acute regulators and circadian clock components is so tight that the discrimination between metabolic and circadian oscillations may be somewhat arbitrary...
- Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1
Sung Hee Um
Department of Genome Science, Genome Research Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, Ohio 45237, USA
Cell Metab 3:393-402. 2006
..Thus, S6K1 may mediate deleterious effects, like insulin resistance, and potentially type 2 diabetes in the face of nutrient excess...
- Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice
William L Holland
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
J Clin Invest 121:1858-70. 2011
..These findings suggest that sphingolipids such as ceramide might be key components of the signaling networks that link lipid-induced inflammatory pathways to the antagonism of insulin action that contributes to diabetes...
- Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men
Department of Medicine, Division of Diabetes, University of Helsinki, FIN 00029 HUCH, Helsinki, Finland
J Clin Endocrinol Metab 87:3023-8. 2002
..sc, and total (determined by magnetic resonance imaging) fat; and insulin sensitivity of endogenous glucose rate of production (R(a)) and suppression of serum FFA [euglycemic insulin clamp combined with [3-(3)H]glucose (0-..
- Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Jason W Locasale
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
Nat Genet 43:869-74. 2011
Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood...
- The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha
The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
Cell 140:280-93. 2010
..Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration...
- Physiological significance of a peripheral tissue circadian clock
Katja A Lamia
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 105:15172-7. 2008
..The liver plays a well known role in glucose homeostasis, and we report here that mice with a liver-specific deletion of Bmal1, an essential clock component, ..
- Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs
Robert J A Frost
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 108:21075-80. 2011
..Here we show that the Let-7 family of microRNAs regulates glucose metabolism in multiple organs...
- T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1
Robert F Margolskee
Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA
Proc Natl Acad Sci U S A 104:15075-80. 2007
Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1)...
- High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushyu University, Fukuoka, Japan
Diabetes 49:1939-45. 2000
..In this study, we examined the effect of high glucose level and free fatty acid (FFA) (palmitate) on ROS production in cultured aortic smooth muscle cells (SMCs) and ..
- Leptin and the central nervous system control of glucose metabolism
Gregory J Morton
Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, Washington 98195, USA
Physiol Rev 91:389-411. 2011
The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes...
- p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, China
Nat Cell Biol 13:310-6. 2011
Cancer cells consume large quantities of glucose and primarily use glycolysis for ATP production, even in the presence of adequate oxygen...
- A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility
Mark P Keller
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53076, USA
Genome Res 18:706-16. 2008
- Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice
L D Klaman
Cancer Biology Program, Division of Hematology Oncology, Boston, Massachusetts 02215, USA
Mol Cell Biol 20:5479-89. 2000
..In addition, insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP-1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp ..
- Evidence for an alternative glycolytic pathway in rapidly proliferating cells
Matthew G Vander Heiden
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Science 329:1492-9. 2010
..cells, including cancer cells, require altered metabolism to efficiently incorporate nutrients such as glucose into biomass...
- Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice
Department of Biology, University of Pennsylvania, Philadelphia 19104, USA
J Biol Chem 276:38349-52. 2001
..However, in striking contrast to Akt2/PKBbeta null mice, Akt1/PKBalpha-deficient mice are normal with regard to glucose tolerance and insulin-stimulated disposal of blood glucose...
- SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase
Vascular Biology Unit and Molecular Cardiology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, and Section of Endocrinology, Boston University, Boston, MA 02118, USA
J Biol Chem 283:20015-26. 2008
..in expression of FAS (fatty acid synthase), and lipid accumulation in human HepG2 hepatocytes exposed to high glucose. These effects of polyphenols are largely abolished by pharmacological and genetic inhibition of SIRT1, ..
- Initiation and execution of lipotoxic ER stress in pancreatic beta-cells
Daniel A Cunha
Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
J Cell Sci 121:2308-18. 2008
..The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary beta-cells is primarily lipotoxic, and not glucolipotoxic...
- Alterations in TCF7L2 expression define its role as a key regulator of glucose metabolism
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA
Genome Res 21:1417-25. 2011
..of the spatial-temporal expression patterns of TCF7L2, including expression in tissues involved in the control of glucose homeostasis...
- Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis
Maria M Mihaylova
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Road, La Jolla, CA 92037, USA
Cell 145:607-21. 2011
..Loss of class IIa HDACs in murine liver results in inhibition of FOXO target genes and lowers blood glucose, resulting in increased glycogen storage...
- Glucose signaling in Saccharomyces cerevisiae
George M Santangelo
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406 5018, USA
Microbiol Mol Biol Rev 70:253-82. 2006
..of signal transduction mechanisms with which to sense and respond to the ubiquitous fermentable carbon source glucose. The budding yeast Saccharomyces cerevisiae has proven to be a fertile model system with which to identify ..
- Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress
Anabela P Rolo
Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, 3004 517 Coimbra, Portugal
Toxicol Appl Pharmacol 212:167-78. 2006
Hyperglycemia resulting from uncontrolled glucose regulation is widely recognized as the causal link between diabetes and diabetic complications...
- Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha
Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA
EMBO J 26:1913-23. 2007
..Consistent with a switch from glucose to fatty acid oxidation that occurs in nutrient deprivation states, SIRT1 is required for induction and ..
- Snowdrift game dynamics and facultative cheating in yeast
Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Nature 459:253-6. 2009
..We are able to alter the outcome of the competition by varying either the cost of cooperation or the glucose concentration in the media...
- TGR5-mediated bile acid sensing controls glucose homeostasis
Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS INSERM ULP, 67404 Illkirch, France
Cell Metab 10:167-77. 2009
..glucagon-like peptide-1 (GLP-1) release, leading to improved liver and pancreatic function and enhanced glucose tolerance in obese mice...
- Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113 8655, Japan
Nature 423:762-9. 2003
..Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice...
- Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies
Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of Arizona, Tucson, AZ 85721 0106, USA
Science 310:486-9. 2005
..Moreover, the presence of related proteins in P-bodies and maternal mRNA storage granules suggests this mechanism is widely adapted for mRNA storage...
- Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells
Institute of Molecular Biology, University of Oregon, Eugene, Oregon, USA
Cancer Res 64:985-93. 2004
..We compared our finding on HeLa cells with those for nontransformed fibroblasts to help distinguish the regulatory pathways...
- Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation
Department of Infectious Diseases, Rigshopitalet University of Copenhagen, Denmark
Diabetes 54:2939-45. 2005
..TNF-alpha infusion in healthy humans induces insulin resistance in skeletal muscle, without effect on endogenous glucose production, as estimated by a combined euglycemic insulin clamp and stable isotope tracer method...
- Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes
R Paul Robertson
Pacific Northwest Research Institute, Seattle, Washington 98122, USA
J Biol Chem 279:42351-4. 2004
- Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113 0033, Japan
Nature 464:1313-9. 2010
..Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes...
- Exercise, glucose transport, and insulin sensitivity
L J Goodyear
Research Division, Joslin Diabetes Center, Brigham and Women s Hospital, Boston, Massachusetts, USA
Annu Rev Med 49:235-61. 1998
..Similarly to insulin, a single bout of exercise increases the rate of glucose uptake into the contracting skeletal muscles, a process that is regulated by the translocation of GLUT4 glucose ..
- Targeting glucose metabolism for cancer therapy
Robert B Hamanaka
Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
J Exp Med 209:211-5. 2012
..Among the metabolic changes exhibited by tumor cells is an increase in glucose metabolism and glucose dependence...
- Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha
Samar I Itani
Diabetes Unit, Section of Endocrinology, Department of Medicine, Boston University Medical Center, Boston, MA, USA
Diabetes 51:2005-11. 2002
..In keeping with previous reports, rates of insulin-stimulated glucose disappearance (G(Rd)) were normal after 2 h but were reduced by 43% (from 52.7 +/- 8.2 to 30.0 +/- 5.3 micromol...
- Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells
Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
Science 325:1555-9. 2009
..cell lines that differed only in the mutational status of their KRAS or BRAF genes, we found that GLUT1, encoding glucose transporter-1, was one of three genes consistently up-regulated in cells with KRAS or BRAF mutations...
- Gone with the Wnts: beta-catenin, T-cell factor, forkhead box O, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism
Stavros C Manolagas
Division of Endocrinology and Metabolism, Department of Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Health Care System, Little Rock, Arkansas 72205 7199, USA
Mol Endocrinol 21:2605-14. 2007
- Brain glucose metabolism in hypothyroidism: a positron emission tomography study before and after thyroid hormone replacement therapy
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus Dresden, Technische Universitat Dresden, Fetscherstrasse 74, Dresden, Germany
J Clin Endocrinol Metab 94:2922-9. 2009
..Hypothyroidism is frequently associated with subtle behavioral and psychiatric symptoms. The consequences of inadequate thyroid hormone availability to brain metabolism are poorly understood...
- Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4092, USA
Science 292:1389-94. 2001
..b>Glucose triggers insulin release from these cell clusters by mechanisms similar to those employed in vivo...
- Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes
J P Silva
Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden
Nat Genet 26:336-40. 2000
..of the mitochondrial membrane potential, impaired Ca(2+)-signalling and lowered insulin release in response to glucose stimulation. We observed reduced beta-cell mass in older mutants...
- Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth
Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
Sci Signal 2:ra73. 2009
The Warburg effect describes a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose even in the presence of oxygen...
- Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA
Dev Cell 14:661-73. 2008
..Here, we have investigated how nutrients (glucose) affect skeletal myogenesis...
- Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1
L F Michael
Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 98:3820-5. 2001
Muscle tissue is the major site for insulin-stimulated glucose uptake in vivo, due primarily to the recruitment of the insulin-sensitive glucose transporter (GLUT4) to the plasma membrane...