A J OURNAL OF THE AMERICAN D IABETE S A SS OCIATION March 2016 Volume 65, Number 3 IN THIS ISSUE 537 598 Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation C. Salomon, K. Scholz-Romero, S. Sarker, E. Sweeney, M. Kobayashi, P. Correa, S. Longo, G. Duncombe, M.D. Mitchell, G.E. Rice, and S.E. Illanes 610 A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents R. Kursawe, V.D. Dixit, P.E. Scherer, N. Santoro, D. Narayan, R. Gordillo, C. Giannini, X. Lopez, B. Pierpont, J. Nouws, G.I. Shulman, and S. Caprio In This Issue of Diabetes COMMENTARIES 539 How Is Proteinuric Diabetic Nephropathy Caused by Disturbed Proteostasis and Autophagy in Podocytes? P.-L. Tharaux and T.B. Huber 542 Emptying the Pool: Modular Insulin Secretion From the Pancreas M.A. Rizzo 545 Insulitis Revisited B.O. Roep 548 The Hypothalamic Melanocortin Pathway and the Regulation of Glucose Handling in the Kidney: A Sympathetic Look at Brain-Kidney Connection S. Obici 551 SIGNAL TRANSDUCTION 619 High Glucose Stimulates Tumorigenesis in Hepatocellular Carcinoma Cells Through AGER-Dependent O-GlcNAcylation of c-Jun Y. Qiao, X. Zhang, Y. Zhang, Y. Wang, Y. Xu, X. Liu, F. Sun, and J. Wang 633 Restoration of Nrf2 Signaling Normalizes the Regenerative Niche M.A. Soares, O.D. Cohen, Y.C. Low, R.A. Sartor, T. Ellison, U. Anil, L. Anzai, J.B. Chang, P.B. Saadeh, P.S. Rabbani, and D.J. Ceradini Hypothalamic Injury: Fish Oil to the Rescue! C. García-Cáceres and M.H. Tschöp METABOLISM 554 Apelin Controls Fetal and Neonatal Glucose Homeostasis and Is Altered by Maternal Undernutrition S. Mayeur, J.-S. Wattez, M.-A. Lukaszewski, S. Lecoutre, L. Butruille, A. Drougard, D. Eberlé, B. Bastide, C. Laborie, L. Storme, C. Knauf, D. Vieau, C. Breton, and J. Lesage 561 Altered Skeletal Muscle Mitochondrial Proteome As the Basis of Disruption of Mitochondrial Function in Diabetic Mice P. Zabielski, I.R. Lanza, S. Gopala, C.J. Holtz Heppelmann, H.R. Bergen III, S. Dasari, and K.S. Nair 574 High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring M. Kruse, F. Keyhani-Nejad, F. Isken, B. Nitz, A. Kretschmer, E. Reischl, T. de las Heras Gala, M.A. Osterhoff, H. Grallert, and A.F.H. Pfeiffer 585 Evidence of Extrapancreatic Glucagon Secretion in Man A. Lund, J.I. Bagger, N.J. Wewer Albrechtsen, M. Christensen, M. Grøndahl, B. Hartmann, E.R. Mathiesen, C.P. Hansen, J.H. Storkholm, G. van Hall, J.F. Rehfeld, D. Hornburg, F. Meissner, M. Mann, S. Larsen, J.J. Holst, T. Vilsbøll, and F.K. Knop Keep up with the latest information for Diabetes and other ADA titles via Facebook (/ADAJournals) and Twitter (@ADA_Journals). All articles in Diabetes are available online at diabetes.org/diabetes, are available free to print subscribers, or can be purchase as e-prints or reprints. ADA’s Diabetes Core Update podcast is available at diabetesjournals .org and through iTunes. OBESITY STUDIES 647 Mesenchymal Stem Cells From Infants Born to Obese Mothers Exhibit Greater Potential for Adipogenesis: The Healthy Start BabyBUMP Project K.E. Boyle, Z.W. Patinkin, A.L.B. Shapiro, P.R. Baker II, D. Dabelea, and J.E. Friedman 660 Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria K.H. Chhabra, J.M. Adams, B. Fagel, D.D. Lam, N. Qi, M. Rubinstein, and M.J. Low 673 n-3 Fatty Acids Induce Neurogenesis of Predominantly POMC-Expressing Cells in the Hypothalamus L.F.R. Nascimento, G.F.P. Souza, J. Morari, G.O. Barbosa, C. Solon, R.F. Moura, S.C. Victório, L.M. Ignácio-Souza, D.S. Razolli, H.F. Carvalho, and L.A. Velloso Icons shown below appear on the first page of an article if more information is available online. ISLET STUDIES 687 Lack of Prox1 Downregulation Disrupts the Expansion and Maturation of Postnatal Murine b-Cells L. Paul, E.M. Walker, Y. Drosos, H.A. Cyphert, G. Neale, R. Stein, J. South, G. Grosveld, P.L. Herrera, and B. Sosa-Pineda 699 Monitoring C-Peptide Storage and Secretion in Islet b-Cells In Vitro and In Vivo S. Zhu, D. Larkin, S. Lu, C. Inouye, L. Haataja, A. Anjum, R. Kennedy, D. Castle, and P. Arvan 803 IMMUNOLOGY AND TRANSPLANTATION 710 Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes L.P. Zhao, S. Alshiekh, M. Zhao, A. Carlsson, H. Elding Larsson, G. Forsander, S.A. Ivarsson, J. Ludvigsson, I. Kockum, C. Marcus, M. Persson, U. Samuelsson, E. Örtqvist, C.-W. Pyo, W.C. Nelson, D.E. Geraghty, and Å. Lernmark, for the Better Diabetes Diagnosis (BDD) Study Group 719 Insulitis and b-Cell Mass in the Natural History of Type 1 Diabetes M. Campbell-Thompson, A. Fu, J.S. Kaddis, C. Wasserfall, D.A. Schatz, A. Pugliese, and M.A. Atkinson 732 Discovery of a Selective Islet Peptidome Presented by the Highest-Risk HLA-DQ8trans Molecule M. van Lummel, P.A. van Veelen, A.H. de Ru, J. Pool, T. Nikolic, S. Laban, A. Joosten, J.W. Drijfhout, I. Gómez-Touriño, S. Arif, H.J. Aanstoot, M. Peakman, and B.O. Roep PATHOPHYSIOLOGY 742 Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat–Fed Diabetic Mice E.E. Mulvihill, E.M. Varin, J.R. Ussher, J.E. Campbell, K.W.A. Bang, T. Abdullah, L.L. Baggio, and D.J. Drucker Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes A. Teumer, A. Tin, R. Sorice, M. Gorski, N.C. Yeo, A.Y. Chu, M. Li, Y. Li, V. Mijatovic, Y.-A. Ko, D. Taliun, A. Luciani, M.-H. Chen, Q. Yang, M.C. Foster, M. Olden, L.T. Hiraki, B.O. Tayo, C. Fuchsberger, A.K. Dieffenbach, A.R. Shuldiner, A.V. Smith, A.M. Zappa, A. Lupo, B. Kollerits, B. Ponte, B. Stengel, B.K. Krämer, B. Paulweber, B.D. Mitchell, C. Hayward, C. Helmer, C. Meisinger, C. Gieger, C.M. Shaffer, C. Müller, C. Langenberg, D. Ackermann, D. Siscovick, DCCT/EDIC, E. Boerwinkle, F. Kronenberg, G.B. Ehret, G. Homuth, G. Waeber, G. Navis, G. Gambaro, G. Malerba, G. Eiriksdottir, G. Li, H.E. Wichmann, H. Grallert, H. Wallaschofski, H. Völzke, H. Brenner, H. Kramer, I.M. Leach, I. Rudan, H.L. Hillege, J.S. Beckmann, J.C. Lambert, J. Luan, J.H. Zhao, J. Chalmers, J. Coresh, J.C. Denny, K. Butterbach, L.J. Launer, L. Ferrucci, L. Kedenko, M. Haun, M. Metzger, M. Woodward, M.J. Hoffman, M. Nauck, M. Waldenberger, M. Pruijm, M. Bochud, M. Rheinberger, N. Verweij, N.J. Wareham, N. Endlich, N. Soranzo, O. Polasek, P. van der Harst, P.P. Pramstaller, P. Vollenweider, P.S. Wild, R.T. Gansevoort, R. Rettig, R. Biffar, R.J. Carroll, R. Katz, R.J.F. Loos, S.-J. Hwang, S. Coassin, S. Bergmann, S.E. Rosas, S. Stracke, T.B. Harris, T. Corre, T. Zeller, T. Illig, T. Aspelund, T. Tanaka, U. Lendeckel, U. Völker, V. Gudnason, V. Chouraki, W. Koenig, Z. Kutalik, J.R. O’Connell, A. Parsa, I.M. Heid, A.D. Paterson, I.H. de Boer, O. Devuyst, J. Lazar, K. Endlich, K. Susztak, J. Tremblay, P. Hamet, H.J. Jacob, C.A. Böger, C.S. Fox, C. Pattaro, and A. Köttgen ERRATUM 818 Erratum. Small Interfering RNA—Mediated Suppression of Proislet Amyloid Polypeptide Expression Inhibits Islet Amyloid Formation and Enhances Survival of Human Islets in Culture. Diabetes 2008;57:3045—3055 L. Marzban, A. Tomas, T.C. Becker, L. Rosenberg, J. Oberholzer, P.E. Fraser, P.A. Halban, and C.B. Verchere ISSUES AND EVENTS COMPLICATIONS 819 755 e-LETTERS – COMMENTS AND RESPONSES 768 Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy A. Tagawa, M. Yasuda, S. Kume, K. Yamahara, J. Nakazawa, M. Chin-Kanasaki, H. Araki, S.-i. Araki, D. Koya, K. Asanuma, E.-H. Kim, M. Haneda, N. Kajiwara, K. Hayashi, H. Ohashi, S. Ugi, H. Maegawa, and T. Uzu miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy B. Feng, Y. Cao, S. Chen, X. Chu, Y. Chu, and S. Chakrabarti e11 Comment on Prior et al. Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining. Diabetes 2015;64:3386–3395 D. Montero e13 Response to Comment on Prior et al. Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining. Diabetes 2015;64:3386–3395 S.J. Prior, A.P. Goldberg, H.K. Ortmeyer, E.R. Chin, D. Chen, J.B. Blumenthal, and A.S. Ryan e15 Comment on Lee et al. Diabetes 2015;64:2836–2846. Comment on Roberts et al. Diabetes 2015;64:471–484 O. Kruszelnicka and A. Surdacki e16 Response to Comment on Lee et al. Diabetes 2015;64:2836– 2846. Comment on Roberts et al. Diabetes 2015;64:471–484 L.D. Roberts, T. Ashmore, A.J. Murray, and J.L. Griffin e17 Response to Comment on Lee et al. Diabetes 2015;64:2836– 2846. Comment on Roberts et al. Diabetes 2015;64:471–484 W.J. Lee and F. Kim PHARMACOLOGY AND THERAPEUTICS 780 An Essential Role of NRF2 in Diabetic Wound Healing M. Long, M. Rojo de la Vega, Q. Wen, M. Bharara, T. Jiang, R. Zhang, S. Zhou, P.K. Wong, G.T. Wondrak, H. Zheng, and D.D. Zhang GENETICS/GENOMES/PROTEOMICS/METABOLOMICS 794 Targeted Deep Sequencing in Multiple-Affected Sibships of European Ancestry Identifies Rare Deleterious Variants in PTPN22 That Confer Risk for Type 1 Diabetes Y. Ge, S. Onengut-Gumuscu, A.R. Quinlan, A.J. Mackey, J.A. Wright, J.H. Buckner, T. Habib, S.S. Rich, and P. Concannon Issues and Events On the cover: Insulitis in a 13-year-old organ donor with type 1 diabetes for 5 years (nPOD 6243). Immune cell phenotypes in insulitic islets were determined by multi-immunofluoresence. An insulitic islet is shown with a lymphocytic infiltrate consisting of both CD31 T cells (pink) and CD201 B cells (green). a-Cells are detected with antiglucagon antibodies (yellow). Photograph courtesy of Martha Campbell-Thompson and Ann Fu of the University of Florida. Their article, “Insulitis and b-Cell Mass in the Natural History of Type 1 Diabetes” (p. 719) and an accompanying article, “Insulitis Revisited” (p. 545), are featured in this issue of Diabetes.