GLUT2, glucose sensing and glucose homeostasis
Reads0
Chats0
TLDR
Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion.Abstract:
The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi–Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.read more
Citations
More filters
Journal ArticleDOI
Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection.
Christoph A. Thaiss,Maayan Levy,Inna Grosheva,Danping Zheng,Eliran Soffer,Eran Blacher,Sofia Braverman,Anouk C. Tengeler,Oren Barak,Oren Barak,Maya Elazar,Rotem Ben-Zeev,Dana Lehavi-Regev,Meirav Katz,Meirav Pevsner-Fischer,Arieh Gertler,Zamir Halpern,Alon Harmelin,Suhail Aamar,Patricia Serradas,Alexandra Grosfeld,Hagit Shapiro,Benjamin Geiger,Eran Elinav +23 more
TL;DR: It is shown in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity, which leads to systemic influx of microbial products and enhanced dissemination of enteric infection.
Journal ArticleDOI
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
TL;DR: Recent advances in understanding of the β-cell transcriptome, electrical activity, and insulin exocytosis are reviewed and models of how the different ion channels contribute to their electrical activity and insulin secretion are provided, and how these processes become perturbed in T2DM are discussed.
Journal ArticleDOI
The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus.
Philipp A. Gerber,Guy A. Rutter +1 more
TL;DR: Better understanding of the role of oxidative changes, its modulation by genes involved in disease risk, and effects on beta-cell identity may facilitate the development of new therapeutic strategies to this disease.
Journal ArticleDOI
Human islets contain four distinct subtypes of β cells.
Craig Dorrell,Jonathan Schug,Pamela S. Canaday,Holger A. Russ,Branden D. Tarlow,Maria T. Grompe,Tamara Horton,Matthias Hebrok,Philip R. Streeter,Klaus H. Kaestner,Markus Grompe +10 more
TL;DR: Four antigenically distinct subtypes of human β cells are identified, which are referred to as β1–4, and which are distinguished by differential expression of ST8SIA1 and CD9, and suggest that this antigenically defined β cell heterogeneity is functionally and likely medically relevant.
Journal ArticleDOI
Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease
Alexandra Chadt,Hadi Al-Hasani +1 more
TL;DR: An array of circulating metabolites and hormone-like molecules and potential supplementary glucose transporters play roles in fine-tuning glucose flux between the different organs in response to an altered energy demand.
References
More filters
Journal ArticleDOI
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
Josée Dupuis,Josée Dupuis,Claudia Langenberg,Inga Prokopenko,Richa Saxena,Richa Saxena,Nicole Soranzo,Nicole Soranzo,Anne U. Jackson,Eleanor Wheeler,Nicole L. Glazer,Nabila Bouatia-Naji,Anna L. Gloyn,Cecilia M. Lindgren,Reedik Mägi,Andrew P. Morris,Joshua C. Randall,Toby Johnson,Toby Johnson,Paul Elliott,Paul Elliott,Denis Rybin,Gudmar Thorleifsson,Valgerdur Steinthorsdottir,Peter Henneman,Harald Grallert,Abbas Dehghan,Jouke JanHottenga,Christopher S. Franklin,Pau Navarro,Kijoung Song,Anuj Goel,John R. B. Perry,Josephine M. Egan,Taina K. Lajunen,Niels Grarup,Thomas Sparsø,Alex S. F. Doney,Benjamin F. Voight,Benjamin F. Voight,Heather M. Stringham,Man Li,Stavroula Kanoni,Peter Shrader,Christine Cavalcanti-Proença,Meena Kumari,Lu Qi,Nicholas J. Timpson,Christian Gieger,Carina Zabena,Ghislain Rocheleau,Erik Ingelsson,Erik Ingelsson,Ping An,Jeffrey R. O'Connell,Jian'an Luan,Amanda F. Elliott,Amanda F. Elliott,Steven A. McCarroll,Steven A. McCarroll,Felicity Payne,Rosa Maria Roccasecca,François Pattou,Praveen Sethupathy,Kristin Ardlie,Yavuz Ariyurek,Beverley Balkau,Philip J. Barter,John Beilby,Yoav Ben-Shlomo,Rafn Benediktsson,Amanda J. Bennett,Sven Bergmann,Sven Bergmann,Murielle Bochud,Eric Boerwinkle,Amélie Bonnefond,Lori L. Bonnycastle,Knut Borch-Johnsen,Knut Borch-Johnsen,Yvonne Böttcher,Eric J. Brunner,Suzannah Bumpstead,Guillaume Charpentier,Yii Der IdaChen,Peter S. Chines,Robert Clarke,Lachlan J. McOin,Mark E. Cooper,Marilyn C. Cornelis,Gabe Crawford,Laura Crisponi,Ian N. M. Day,Eco J. C. de Geus,Jérôme Delplanque,Christian Dina,Michael R. Erdos,A C Fedson,Antje Fischer-Rosinsky,Nita G. Forouhi,Caroline S. Fox,Caroline S. Fox,Rune R. Frants,Maria GraziaFranzosi,Pilar Galan,Mark O. Goodarzi,J. Graessler,Christopher J. Groves,Scott M. Grundy,Rhian Gwilliam,Ulf Gyllensten,Samy Hadjadj,Göran Hallmans,Naomi Hammond,Xijing Han,Anna LiisaHartikainen,Neelam Hassanali,Caroline Hayward,Simon Heath,Serge Hercberg,Christian Herder,Andrew A. Hicks,David R. Hillman,Aroon D. Hingorani,Albert Hofman,Jennie Hui,Joseph Hung,Joseph Hung,Bo Isomaa,Paul Johnson,Torben Jørgensen,Antti Jula,Marika Kaakinen,Jaakko Kaprio,Jaakko Kaprio,Y. AnteroKesaniemi,Mika Kivimäki,Beatrice Knight,Seppo Koskinen,Peter Kovacs,Kirsten Ohm Kyvik,G. Mark Lathrop,Debbie A Lawlor,Olivier Le Bacquer,Cécile Lecoeur,Yun Li,Valeriya Lyssenko,Robert W. Mahley,Massimo Mangino,Alisa K. Manning,María TeresaMartínez-Larrad,Jarred B. McAteer,Jarred B. McAteer,Laura J. McCulloch,Ruth McPherson,Christa Meisinger,David Melzer,David Meyre,Braxton D. Mitchell,Mario A. Morken,Sutapa Mukherjee,Silvia Naitza,Narisu Narisu,Matt Neville,Ben A. Oostra,Marco Orrù,Ruth E. Pakyz,Colin N. Apalmer,Giuseppe Paolisso,Cristian Pattaro,Daniel S. Pearson,John F. Peden,Nancy L. Pedersen,Markus Perola,Markus Perola,Andreas Pfeiffer,Irene Pichler,Ozren Polasek,Danielle Posthuma,Simon C. Potter,Anneli Pouta,Michael A. Province,Bruce M. Psaty,Bruce M. Psaty,Wolfgang Rathmann,Nigel W. Rayner,Kenneth Rice,Samuli Ripatti,Samuli Ripatti,Fernando Rivadeneira,Michael Roden,Olov Rolandsson,Annelli Sandbæk,Manjinder S. Sandhu,Serena Sanna,Avan Aihie Sayer,Paul Scheet,Laura J. Scott,Udo Seedorf,Stephen J. Sharp,Beverley M. Shields,Gunnar Sigursson,Eric J.G. Sijbrands,Angela Silveira,Laila Simpson,Andrew B. Singleton,Nicholas L. Smith,Nicholas L. Smith,Ulla Sovio,Amy J. Swift,Holly E. Syddall,Ann ChristineSyvänen,Toshiko Tanaka,Toshiko Tanaka,Barbara Thorand,Jean Tichet,Anke Tönjes,Tiinamaija Tuomi,André G. Uitterlinden,Ko Willems van Dijk,Mandy van Hoek,Dhiraj Varma,Sophie Visvikis-Siest,Veronique Vitart,Nicole Vogelzangs,Gerard Waeber,Peter Wagner,Peter Wagner,Andrew Walley,G. BragiWalters,Kim L. Ward,Hugh Watkins,Michael N. Weedon,Sarah H. Wild,Gonneke Willemsen,Jaqueline C. MWitteman,John W. GYarnell,Eleftheria Zeggini,Eleftheria Zeggini,Diana Zelenika,Björn Zethelius,Björn Zethelius,Guangju Zhai,Jing Hua Zhao,M. Carola Zillikens,Ingrid B. Borecki,Ruth J. F. Loos,Pierre Meneton,Patrik K. E. Magnusson,David M. Nathan,Gordon H. Williams,Andrew T. Hattersley,Kaisa Silander,Kaisa Silander,Veikko Salomaa,George Davey Smith,Stefan R. Bornstein,Peter Schwarz,Joachim Spranger,Fredrik Karpe,Alan R. Shuldiner,Cyrus Cooper,George Dedoussis,Manuel Serrano-Ríos,Andrew D. Morris,Lars Lind,Lyle J. Palmer,Lyle J. Palmer,Frank B. Hu,Paul W. Franks,Shah Ebrahim,Michael Marmot,W. H. Linda Kao,James S. Pankow,Mike Sampson,Johanna Kuusisto,Markku Laakso,Torben Hansen,Torben Hansen,Oluf Pedersen,Oluf Pedersen,Oluf Pedersen,Peter P. Pramstaller,H.-Erich Wichmann,Thomas Illig,Igor Rudan,Igor Rudan,Alan F. Wright,Michael Stumvoll,Harry Campbell,James F. Wilson,Richard N. Bergman,Thomas A. Buchanan,Francis S. Collins,Karen L. Mohlke,Jaakko Tuomilehto,Jaakko Tuomilehto,Timo T. Valle,David Altshuler,David Altshuler,Jerome I. Rotter,David S. Siscovick,Brenda W.J.H. Penninx,Dorret I. Boomsma,Panos Deloukas,Tim D. Spector,Tim D. Spector,Timothy M. Frayling,Luigi Ferrucci,Augustine Kong,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Kari Stefansson,Kari Stefansson,Cornelia M. van Duijn,Yurii S. Aulchenko,Antonio Cao,Angelo Scuteri,David Schlessinger,Manuela Uda,Aimo Ruokonen,Marjo Riitta-Järvelin,Marjo Riitta-Järvelin,Dawn M. Waterworth,Peter Vollenweider,Leena Peltonen,Vincent Mooser,Gonçalo R. Abecasis,Nicholas J. Wareham,Robert Sladek,Philippe Froguel,Philippe Froguel,Richard M. Watanabe,James B. Meigs,Leif Groop,Michael Boehnke,Mark I. McCarthy,Jose C. Florez,Jose C. Florez,Inês Barroso +339 more
TL;DR: It is demonstrated that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Journal Article
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (vol 42, pg 105, 2010)
Josée Dupuis,Claudia Langenberg,Inga Prokopenko,Richa Saxena,Nicole Soranzo,Anne U. Jackson,Eleanor Wheeler,Nicole L. Glazer,Nabila Bouatia-Naji,Anna L. Gloyn,C M Lindgren,Reedik Mägi,Andrew P. Morris,Joshua C. Randall,Toby Johnson,Peter J. Elliott,D Rybin,Gudmar Thorleifsson,Steinthorsdottir,Peter Henneman,H Grallert,Abbas Dehghan,J-J Hottenga,Christopher S. Franklin,Pau Navarro,KJ Song,Anuj Goel,Jrb Perry,Josephine M. Egan,Taina K. Lajunen,Niels Grarup,Thomas Sparsø,Alex S. F. Doney,B F Voight,Heather M. Stringham,Man Li,Stavroula Kanoni,Peter Shrader,Christine Cavalcanti-Proença,Meena Kumari,Lu Qi,N J Timpson,Christian Gieger,Carina Zabena,Ghislain Rocheleau,Erik Ingelsson,Ping An,Jeffery R. O'Connell,Jian'an Luan,Amanda F. Elliott,Steve McCarroll,Felicity Payne,Rosa Maria Roccasecca,François Pattou,Praveen Sethupathy,Kristin G. Ardlie,Yavuz Ariyurek,B. Balkau,Philip J. Barter,John Beilby,Yoav Ben-Shlomo,Rafn Benediktsson,Amanda J. Bennett,Sven Bergmann,Murielle Bochud,Eric Boerwinkle,Amélie Bonnefond,Lori L. Bonnycastle,Knut Borch-Johnsen,Yvonne Böttcher,Eric J. Brunner,Suzannah Bumpstead,Guillaume Charpentier,Ydi Chen,Peter S. Chines,Robert Clarke,Ljm Coin,Mark E. Cooper,Marilyn C. Cornelis,Gabriel Crawford,Laura Crisponi,Inm Day,Ejc de Geus,Jérôme Delplanque,Christian Dina,Erdos,A C Fedson,Antje Fischer-Rosinsky,Nita G. Forouhi,Caroline S. Fox,Rune R. Frants,MariaGrazia Franzosi,Pilar Galan,Mark O. Goodarzi,J. Graessler,C J Groves,Scott M. Grundy,R. Gwilliam,Ulf Gyllensten,Samy Hadjadj,Göran Hallmans,Naomi Hammond,Xijing Han,A.-L. Hartikainen,N Hassanali,Caroline Hayward,Simon C. Heath,Serge Hercberg,Christian Herder,Andrew A. Hicks,Hillman,Aroon D. Hingorani,A. Hofman,Jennie Hui,Joseph Hung,Bo Isomaa,Prv Johnson,Torben Jørgensen,A. Jula,Marika Kaakinen,J Kaprio,Y A Kesaniemi,Mika Kivimäki,Beatrice Knight,Seppo Koskinen,Peter Kovacs,Kirsten Ohm Kyvik,G. M. Lathrop,Debbie A Lawlor,O Le Bacquer,C. Lecoeur,Yun Li,Lyssenko,Robert W. Mahley,Massimo Mangino,Alisa K. Manning,María Teresa Martínez-Larrad,Jarred B. McAteer,Laura J. McCulloch,Ruth McPherson,Christine Meisinger,David Melzer,David Meyre,Braxton D. Mitchell,M. A. Morken,Sutapa Mukherjee,Silvia Naitza,Narisu Narisu,Matt J. Neville,Ben A. Oostra,Marco Orrù,Ruth E. Pakyz,Cna Palmer,Giuseppe Paolisso,Cristian Pattaro,Daniel S. Pearson,J F Peden,Nancy L. Pedersen,M. Perola,Afh Pfeiffer,Irene Pichler,Ozren Polasek,Danielle Posthuma,Simon C. Potter,A Pouta,M. A. Province,Bruce M. Psaty,Wolfgang Rathmann,N W Rayner,Kenneth Rice,S. Ripatti,Fernando Rivadeneira,Michael Roden,Olov Rolandsson,A. Sandbaek,M. S. Sandhu,Serena Sanna,Avan Aihie Sayer,Paul Scheet,Laura J. Scott,Udo Seedorf,Stephen J. Sharp,B M Shields,G Sigurosson,Ejg Sijbrands,Angela Silveira,Laila Simpson,AB Singleton,Nicholas L. Smith,Ulla Sovio,Amy J. Swift,Holly E. Syddall,Ann-Christine Syvänen,Toshiko Tanaka,Barbara Thorand,Jean Tichet,A Tönjes,Tiinamaija Tuomi,A.G. Uitterlinden,K W van Dijk,M. van Hoek,Dhiraj Varma,Sophie Visvikis-Siest,Vitart,Nicole Vogelzangs,G. Waeber,P J Wagner,Andrew Walley,G B Walters,Kim L. Ward,Hugh Watkins,Michael N. Weedon,Sarah H. Wild,Gonneke Willemsen,Jcm Witteman,Jwg Yarnell,E Zeggini,Diana Zelenika,Björn Zethelius,Guangju Zhai,Jing Hua Zhao,M. C. Zillikens,Ingrid B. Borecki,Rjf Loos,Pierre Meneton,Pke Magnusson,David M. Nathan,Gordon H. Williams,Andrew T. Hattersley,Kaisa Silander,Salomaa,George Davey Smith,Bornstein,Peter Schwarz,Jochen Spranger,F Karpe,A. R. Shuldiner,Cyrus Cooper,George Dedoussis,Manuel Serrano-Ríos,Andrew D. Morris,Lars Lind,Lyle J. Palmer,Frank B. Hu,Paul W. Franks,S Ebrahim,Michael Marmot,Whl Kao,James S. Pankow,Mike Sampson,Johanna Kuusisto,Markku Laakso,T. Hansen,Oluf Pedersen,Peter P. Pramstaller,Heinz Erich Wichmann,Thomas Illig,Igor Rudan,Alan F. Wright,Michael Stumvoll,Harry Campbell,James F. Wilson,Anders Hamsten,Richard N. Bergman,Thomas A. Buchanan,F. S. Collins,Karen L. Mohlke,J. Tuomilehto,Valle Tt,David Altshuler,Jerome I. Rotter,David S. Siscovick,Bwjh Penninx,D.I. Boomsma,Panagiotis Deloukas,Tim D. Spector,Timothy M. Frayling,L Ferrucci,Augustine Kong,Unnur Thorsteinsdottir,Kari Stefansson,C M van Duijn,Y S Aulchenko,Anyuan Cao,Angelo Scuteri,David Schlessinger,Manuela Uda,Aimo Ruokonen,Jarvelin,Dawn M. Waterworth,Peter Vollenweider,Leena Peltonen,Mooser,Gonçalo R. Abecasis,Nicholas J. Wareham,Robert Sladek,Philippe Froguel,Richard M. Watanabe,James B. Meigs,Leif Groop,Michael Boehnke,Mark I. McCarthy,Jose C. Florez,Ines Barroso Magic Investigators +303 more
Journal ArticleDOI
The Development and Application of Optogenetics
TL;DR: The development of currently available single-component optogenetic tools is outlined and the application of various optogenetics tools in diverse model organisms is summarized.
Journal ArticleDOI
Hemorrhages into peripheral nerves in association with leukemia.
Journal ArticleDOI
The receptors and cells for mammalian taste
TL;DR: The emerging picture of taste coding at the periphery is one of elegant simplicity, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes.