title: Adiponectin-SOGA Dissociation in Type 1 Diabetes.
abstract: BACKGROUND
  Circulating adiponectin is elevated in human type 1 diabetes (T1D) and nonobese diabetic (NOD) mice without the expected indications of adiponectin action, consistent with tissue resistance.
  
  
  OBJECTIVE
  Adiponectin stimulates hepatocyte production of the suppressor of glucose from autophagy (SOGA), a protein that inhibits glucose production. We postulated that due to tissue resistance, the elevation of adiponectin in T1D should fail to increase the levels of a surrogate marker for liver SOGA, the circulating C-terminal SOGA fragment.
  
  
  METHODS
  Liver and plasma SOGA were measured in NOD mice (n = 12) by Western blot. Serum adiponectin and SOGA were measured in T1D and control (Ctrl) participants undergoing a three-stage insulin clamp for the Coronary Artery Calcification in T1D study (n = 20). Glucose turnover was measured using 6,6[(2)H2]glucose (n = 12).
  
  
  RESULTS
  In diabetic NOD mice, the 13%-29% decrease of liver SOGA (P = .003) and the 30%-37% reduction of circulating SOGA (P < .001) were correlated (r = 0.826; P = .001). In T1D serum, adiponectin was 50%-60% higher than Ctrl, SOGA was 30%-50% lower and insulin was 3-fold higher (P < .05). At the low insulin infusion rate (4 mU/m(2)·min), the resulting glucose appearance correlated negatively with adiponectin in T1D (r = -0.985, P = .002) and SOGA in Ctrl and T1D (r = -0.837, P = .001). Glucose disappearance correlated with adiponectin in Ctrl (r = -0.757, P = .049) and SOGA in Ctrl and T1D (r = -0.709, P = .010). At 40 mU/m(2)·min, the lowered glucose appearance was similar in Ctrl and T1D. Glucose disappearance increased only in Ctrl (P = .005), requiring greater glucose infusion to maintain euglycemia (8.58 ± 1.29 vs 3.09 ± 0.87 mg/kg·min; P = .009).
  
  
  CONCLUSIONS
  The correlation between liver and plasma SOGA in NOD mice supports the use of the latter as surrogate marker for liver concentration. Reduced SOGA in diabetic NOD mice suggests resistance to adiponectin. The dissociation between adiponectin and SOGA in T1D raises the possibility that restoring adiponectin signaling and SOGA might improve the metabolic response to insulin therapy.
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Combs
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Bergman
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Marie
authors.initials: M
authors.lastname: Lamarche
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Laura
authors.initials: L
authors.lastname: Iberkleid
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Omar
authors.initials: O
authors.lastname: AbdelBaky
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Roland
authors.initials: R
authors.lastname: Tisch
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.affiliation: Department of Medicine (T.P.C., L.I., O.A.), Department of Microbiology and Immunology (R.T.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Crabtree Nutrition Laboratories (T.P.C., M.L., E.B.M.), Department of Medicine, McGill University, Montréal, Québec, Canada H4A 3J1; Barbara Davis Center for Childhood Diabetes (J.K.S.-B., D.M.M., B.C.B.), Department of Medicine, University of Colorado, Anschutz Medical Campus, Denver, Colorado 80045; and Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
authors.forename: Errol B
authors.initials: EB
authors.lastname: Marliss
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000818:Animals; D000071183:Autophagy-Related Proteins; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D000071183:Autophagy-Related Proteins; D001786:Blood Glucose; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C000602895:SOGA1 protein, human; C556442:suppressor of glucose by autophagy protein, mouse