ALAN SALTIEL

Summary

Affiliation: University of Michigan
Country: USA

Publications

  1. ncbi request reprint Staying in SHIP shape
    Stuart J Decker
    Nat Med 11:123-4. 2005
  2. ncbi request reprint Cloning and functional characterization of related TC10 isoforms, a subfamily of Rho proteins involved in insulin-stimulated glucose transport
    Shian Huey Chiang
    Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, MI 48109 0650, USA
    J Biol Chem 277:13067-73. 2002
  3. pmc An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice
    Shannon M Reilly
    Life Sciences Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Nat Med 19:313-21. 2013
  4. ncbi request reprint 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
  5. ncbi request reprint Insulin signaling in microdomains of the plasma membrane
    Alan R Saltiel
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 0650, USA
    Traffic 4:711-6. 2003
  6. ncbi request reprint Insulin signaling pathways in time and space
    Alan R Saltiel
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 0650, USA
    Trends Cell Biol 12:65-71. 2002
  7. ncbi request reprint The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport
    Jun Liu
    Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    J Biol Chem 278:36754-62. 2003
  8. ncbi request reprint Insulin htts on autophagy
    Carey N Lumeng
    Life Sciences Institute, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109, USA
    Autophagy 2:250-3. 2006
  9. pmc APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes
    Jun Liu
    Department of Internal Medicine and Physiology, Life Science Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Mol Cell Biol 22:3599-609. 2002
  10. ncbi request reprint The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin
    Mayumi Inoue
    Life Sciences Institute, Departments of Internal Medicine and Physiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Nature 422:629-33. 2003

Research Grants

  1. The role of the Exocyst complex in insulin regulated glucose transport
    ALAN SALTIEL; Fiscal Year: 2007
  2. The Role of G Proteins in Insulin Action
    ALAN SALTIEL; Fiscal Year: 2009
  3. Hormonal Regulation of Glycogen Synthesis
    Alan R Saltiel; Fiscal Year: 2010
  4. Signaling Pathways in Insulin Action
    Alan R Saltiel; Fiscal Year: 2010
  5. The Role of G Proteins in Insulin Action
    Alan R Saltiel; Fiscal Year: 2010
  6. The role of the Exocyst complex in insulin regulated glucose transport
    Alan R Saltiel; Fiscal Year: 2010
  7. The Role of G Proteins in Insulin Action
    ALAN SALTIEL; Fiscal Year: 2007
  8. Hormonal Regulation of Glycogen Synthesis
    ALAN SALTIEL; Fiscal Year: 2007
  9. The Role of G Protein in Insulin Action
    ALAN SALTIEL; Fiscal Year: 2006
  10. Hormonal Regulation of Glycogen Synthesis
    ALAN SALTIEL; Fiscal Year: 2006

Collaborators

  • MARK A STAMNES
  • Jun O Liu
  • Mayumi Inoue
  • Jeffrey E Pessin
  • Makoto Kanzaki
  • Dan F Lazar
  • Stevan R Hubbard
  • Shian Huey Chiang
  • Louise Chang
  • Carey N Lumeng
  • Irfan J Lodhi
  • Alan Cheng
  • Xiao Wei Chen
  • Stuart J Decker
  • Shannon M Reilly
  • Robert T Watson
  • Jonathan Mowers
  • Sean M Crosson
  • Nicole M White
  • Lynn M Geletka
  • Akiko Kimura
  • Kazuho Kawase
  • Xiong Su
  • Mei Zhang
  • Pierre Voisine
  • Junjie Hu
  • Joseph Hwang
  • Ruth T Yu
  • Irit Hochberg
  • Dayoung Oh
  • Pingping Li
  • Jerrold M Olefsky
  • Christopher Liddle
  • Martha J Larsen
  • Michael Downes
  • Maeran Uhm
  • Ronald M Evans
  • John R Rubin
  • Dan Westcott
  • Fiona E Yull
  • Timothy S Blackwell
  • Nathan Qi
  • Jennifer B Delproposto
  • Jie Zhou
  • Jing Tyan Ma
  • Merlijn Bazuine
  • Yanling Zhang
  • Dave Bridges
  • Lois S Weisman
  • Jennifer L Bodzin
  • Stephanie M Deyoung
  • Dara Leto
  • Qian Wang
  • Daniel Vollenweider
  • Takeshi Nakamura
  • Hiroshi Kiyama
  • Hiroshi Takemoto
  • Michiyuki Matsuda
  • Kazuhiko Namikawa
  • Shuichiro Inagaki
  • Akiyuki Takaya
  • Philip D Stahl
  • Kazuhiro Aoki
  • Zhao Q Bao
  • Cesario Bianchi
  • Towia A Libermann
  • Frank W Sellke
  • Hasan Otu
  • Shu Hua Xu
  • Tanveer A Khan
  • Isaac Kohane
  • Marc Ruel
  • Rodolfo Ghirlando
  • Megumi Furukawa
  • Ahmir Khan
  • John Printen
  • Diana Boeglin
  • Marie Legendre
  • Silvia Mora
  • June Chunqiu Hou
  • Satoshi Shigematsu
  • Rachael D Adams

Detail Information

Publications40

  1. ncbi request reprint Staying in SHIP shape
    Stuart J Decker
    Nat Med 11:123-4. 2005
  2. ncbi request reprint Cloning and functional characterization of related TC10 isoforms, a subfamily of Rho proteins involved in insulin-stimulated glucose transport
    Shian Huey Chiang
    Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, MI 48109 0650, USA
    J Biol Chem 277:13067-73. 2002
    ..Thus, there are two isoforms of this key signaling intermediate, both of which are activated by insulin, but they may play different roles in initiating downstream effectors that influence glucose transport...
  3. pmc An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice
    Shannon M Reilly
    Life Sciences Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Nat Med 19:313-21. 2013
    ..Because of its record of safety in patients, amlexanox may be an interesting candidate for clinical evaluation in the treatment of obesity and related disorders...
  4. ncbi request reprint 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
    ..But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes...
  5. ncbi request reprint Insulin signaling in microdomains of the plasma membrane
    Alan R Saltiel
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 0650, USA
    Traffic 4:711-6. 2003
    ..These events play crucial roles in the trafficking, docking and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 at the plasma membrane...
  6. ncbi request reprint Insulin signaling pathways in time and space
    Alan R Saltiel
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 0650, USA
    Trends Cell Biol 12:65-71. 2002
    ..Also, the rapid termination of tyrosine or lipid phosphorylation by phosphatases or serine kinases might tightly control the strength of a signaling pathway, thus determining its effect on growth, differentiation and metabolism...
  7. ncbi request reprint The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport
    Jun Liu
    Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    J Biol Chem 278:36754-62. 2003
    ..Thus, both c-Cbl and Cbl-b can initiate a phosphatidylinositol 3-kinase/protein kinase B-independent signaling pathway critical to insulin-stimulated GLUT4 translocation...
  8. ncbi request reprint Insulin htts on autophagy
    Carey N Lumeng
    Life Sciences Institute, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109, USA
    Autophagy 2:250-3. 2006
    ..This suggests that insulin/insulin-like growth factor signaling pathways not only prevent the induction of autophagy, but paradoxically may promote autophagy of deleterious proteins in certain circumstances...
  9. pmc APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes
    Jun Liu
    Department of Internal Medicine and Physiology, Life Science Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Mol Cell Biol 22:3599-609. 2002
    ....
  10. ncbi request reprint The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin
    Mayumi Inoue
    Life Sciences Institute, Departments of Internal Medicine and Physiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Nature 422:629-33. 2003
    ..So, the exocyst might have a crucial role in the targeting of the Glut4 vesicle to the plasma membrane, perhaps directing the vesicle to the precise site of fusion...
  11. pmc TCGAP, a multidomain Rho GTPase-activating protein involved in insulin-stimulated glucose transport
    Shian Huey Chiang
    Life Sciences Institute, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48109 0650, USA
    EMBO J 22:2679-91. 2003
    ..Thus, TCGAP may act as a downstream effector of TC10 in the regulation of insulin-stimulated glucose transport...
  12. pmc Insulin signaling and the regulation of glucose transport
    Louise Chang
    Life Sciences Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
    Mol Med 10:65-71. 2004
    ..These pathways converge to control the recycling of the facilitative glucose transporter Glut4...
  13. ncbi request reprint TC10alpha is required for insulin-stimulated glucose uptake in adipocytes
    Louise Chang
    Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109 2216, USA
    Endocrinology 148:27-33. 2007
    ..Additionally, knockdown of TC10alpha inhibited insulin-stimulated translocation of its effector CIP4. These data indicate that TC10alpha is specifically required for insulin-stimulated glucose uptake in adipocytes...
  14. pmc The TC10-interacting protein CIP4/2 is required for insulin-stimulated Glut4 translocation in 3T3L1 adipocytes
    Louise Chang
    Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 99:12835-40. 2002
    ..These data suggest that CIP4/2 may play an important role in insulin-stimulated glucose transport as a downstream effector of TC10...
  15. pmc PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance
    Sean M Crosson
    Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 0650, USA
    J Clin Invest 111:1423-32. 2003
    ..These data suggest that PTG plays a critical role in glycogen synthesis and is necessary to maintain the appropriate metabolic balance for the partitioning of fuel substrates between glycogen and lipid...
  16. pmc Compartmentalization of the exocyst complex in lipid rafts controls Glut4 vesicle tethering
    Mayumi Inoue
    Life Sciences Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
    Mol Biol Cell 17:2303-11. 2006
    ..These results suggest that the TC10/exocyst complex/SAP97 axis plays an important role in the tethering of Glut4 vesicles to the plasma membrane in adipocytes...
  17. ncbi request reprint TC10 and insulin-stimulated glucose transport
    Shian Huey Chiang
    Life Sciences Institute, University of Michigan, Ann Arbor, USA
    Methods Enzymol 406:701-14. 2006
    ..We describe experimental approaches using the insulin-responsive cell line 3T3-L1 adipocytes to study the role of TC10 in insulin-stimulated glucose transport...
  18. pmc Insulin stimulates phosphatidylinositol 3-phosphate production via the activation of Rab5
    Irfan J Lodhi
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Mol Biol Cell 19:2718-28. 2008
    ..Together, these studies suggest that the TC10/GAPEX-5/Rab5 axis mediates insulin-stimulated production of PI(3)P, which regulates trafficking of Glut4 vesicles...
  19. ncbi request reprint More TORC for the gluconeogenic engine
    Alan Cheng
    Department of Internal Medicine, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, 48109, USA
    Bioessays 28:231-4. 2006
    ..Thus, TORC2 might serve as a gluconeogenic "molecular switch" that senses hormones and cellular energy status...
  20. ncbi request reprint The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1
    Akiko Kimura
    Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 0650, USA
    J Biol Chem 277:30153-8. 2002
    ..Taken together, these data indicate that the insulin receptor directly catalyzes the tyrosine phosphorylation of caveolin...
  21. ncbi request reprint Putting the brakes on insulin signaling
    Alan R Saltiel
    Life Sciences Institute, University of Michigan, Ann Arbor, USA
    N Engl J Med 349:2560-2. 2003
  22. ncbi request reprint Changes in integrin expression during adipocyte differentiation
    Jun Liu
    Department of Internal Medicine, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Cell Metab 2:165-77. 2005
    ..These findings demonstrate a role for integrin alpha6 in connecting morphogenesis with signaling processes leading to terminal differentiation...
  23. pmc Obesity induces a phenotypic switch in adipose tissue macrophage polarization
    Carey N Lumeng
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Clin Invest 117:175-84. 2007
    ..Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance...
  24. ncbi request reprint TIRFing out studies on Glut4 trafficking
    Xiao Wei Chen
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Dev Cell 12:4-5. 2007
  25. pmc Gapex-5, a Rab31 guanine nucleotide exchange factor that regulates Glut4 trafficking in adipocytes
    Irfan J Lodhi
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell Metab 5:59-72. 2007
    ..Insulin recruits the CIP4/Gapex-5 complex to the plasma membrane, thus reducing Rab31 activity and permitting Glut4 vesicles to translocate to the cell surface, where Glut4 docks and fuses to transport glucose into the cell...
  26. pmc Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins
    Carey N Lumeng
    Life Sciences Institute, 210 Washtenaw Ave, Ann Arbor, MI 48109, USA
    Am J Physiol Endocrinol Metab 292:E166-74. 2007
    ..Thus both indirect/secreted and direct/cell contact-mediated factors derived from macrophages influence insulin sensitivity in adipocytes...
  27. ncbi request reprint Activation of RalA is required for insulin-stimulated Glut4 trafficking to the plasma membrane via the exocyst and the motor protein Myo1c
    Xiao Wei Chen
    Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Dev Cell 13:391-404. 2007
    ..Thus, RalA serves two functions in insulin action: as a cargo receptor for the Myo1c motor, and as a signal for the unification of the exocyst to target Glut4 vesicles to the plasma membrane...
  28. pmc The protein kinase IKKepsilon regulates energy balance in obese mice
    Shian Huey Chiang
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 138:961-75. 2009
    ..Thus, IKKepsilon may represent an attractive therapeutic target for obesity, insulin resistance, diabetes, and other complications associated with these disorders...
  29. ncbi request reprint Regulation of the mouse protein targeting to glycogen (PTG) promoter by the FoxA2 forkhead protein and by 3',5'-cyclic adenosine 5'-monophosphate in H4IIE hepatoma cells
    Alan Cheng
    Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, 48109, USA
    Endocrinology 147:3606-12. 2006
    ..Our results provide a framework to investigate how additional transcription factors may regulate PTG expression in other cell types...
  30. ncbi request reprint Lipid phosphatases as drug discovery targets for type 2 diabetes
    Dan F Lazar
    Eli Lilly and Co, Endocrine Division, Lilly Research Laboratories, Indianapolis, Indianapolis 46285, USA
    Nat Rev Drug Discov 5:333-42. 2006
    ..Both in vivo and in vitro studies indicate their role in regulating whole-body energy metabolism, and possibly weight gain as well. The promise and challenges presented by this new class of drug discovery targets will also be discussed...
  31. ncbi request reprint A TUG on glucose transport
    Alan R Saltiel
    Nat Med 9:1352. 2003
  32. pmc Atypical protein kinase C (PKCzeta/lambda) is a convergent downstream target of the insulin-stimulated phosphatidylinositol 3-kinase and TC10 signaling pathways
    Makoto Kanzaki
    Dept of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794 8651, USA
    J Cell Biol 164:279-90. 2004
    ....
  33. ncbi request reprint Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5
    Xiong Su
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:27982-90. 2006
    ..Down-regulation of GAPex-5 impaired insulin-stimulated PKB/Akt activation. Collectively, this study indicates the involvement of Rab5 in insulin signaling...
  34. pmc The exocytotic trafficking of TC10 occurs through both classical and nonclassical secretory transport pathways in 3T3L1 adipocytes
    Robert T Watson
    Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242, USA
    Mol Cell Biol 23:961-74. 2003
    ..Moreover, the transport through the secretory pathway is necessary for the localization of TC10 to lipid raft microdomains at the plasma membrane...
  35. pmc Small GTP-binding protein TC10 differentially regulates two distinct populations of filamentous actin in 3T3L1 adipocytes
    Makoto Kanzaki
    Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242, USA
    Mol Biol Cell 13:2334-46. 2002
    ..Together, these data demonstrate that TC10 can differentially regulate two types of filamentous actin in adipocytes dependent on distinct functional domains and its subcellular compartmentalization...
  36. ncbi request reprint GTP hydrolysis by the Rho family GTPase TC10 promotes exocytic vesicle fusion
    Kazuho Kawase
    Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Dev Cell 11:411-21. 2006
    ..We propose that an EGF-stimulated GAP accelerates GTP hydrolysis of TC10, thereby promoting vesicle fusion...
  37. ncbi request reprint Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor
    Junjie Hu
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 12:1379-89. 2003
    ..This structure provides a molecular visualization of one of the initial downstream recruitment events following insulin activation of its dimeric receptor...
  38. ncbi request reprint Differences in gene expression profiles of diabetic and nondiabetic patients undergoing cardiopulmonary bypass and cardioplegic arrest
    Pierre Voisine
    Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass 02215, USA
    Circulation 110:II280-6. 2004
    ..We sought to compare the cardiac gene expression responses to cardiopulmonary bypass (CPB) and cardioplegic arrest (C) in patients with and without diabetes...
  39. ncbi request reprint Holding the line on hepatic fat
    Alan R Saltiel
    Cell Metab 2:1-2. 2005
    ..However, the hormone reduces liver lipids when acutely elevated. Work in this issue of Cell Metabolism (Najjar at al., 2005) suggests a new mechanism for the inhibition of the rate-limiting enzyme in liver, fatty acid synthase...

Research Grants31

  1. The role of the Exocyst complex in insulin regulated glucose transport
    ALAN SALTIEL; Fiscal Year: 2007
    ..We anticipate that these data will present a clearer picture of the regulation of Glut4 trafficking, docking and fusion. ..
  2. The Role of G Proteins in Insulin Action
    ALAN SALTIEL; Fiscal Year: 2009
    ..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..
  3. Hormonal Regulation of Glycogen Synthesis
    Alan R Saltiel; Fiscal Year: 2010
    ....
  4. Signaling Pathways in Insulin Action
    Alan R Saltiel; Fiscal Year: 2010
    ....
  5. The Role of G Proteins in Insulin Action
    Alan R Saltiel; Fiscal Year: 2010
    ..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..
  6. The role of the Exocyst complex in insulin regulated glucose transport
    Alan R Saltiel; Fiscal Year: 2010
    ..We anticipate that these data will present a clearer picture of the regulation of Glut4 trafficking, docking and fusion. ..
  7. The Role of G Proteins in Insulin Action
    ALAN SALTIEL; Fiscal Year: 2007
    ..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..
  8. Hormonal Regulation of Glycogen Synthesis
    ALAN SALTIEL; Fiscal Year: 2007
    ....
  9. The Role of G Protein in Insulin Action
    ALAN SALTIEL; Fiscal Year: 2006
    ..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..
  10. Hormonal Regulation of Glycogen Synthesis
    ALAN SALTIEL; Fiscal Year: 2006
    ..Together, these approaches will allow for the evaluation of the importance of this pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..
  11. Signaling Pathways in Insulin Action
    ALAN SALTIEL; Fiscal Year: 2006
    ..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..
  12. The Role of G Proteins in Insulin Action
    Alan R Saltiel; Fiscal Year: 2010
    ..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..