title: Cardiac-Specific Disruption of GH Receptor Alters Glucose Homeostasis While Maintaining Normal Cardiac Performance in Adult Male Mice.
abstract: GH is considered necessary for the proper development and maintenance of several tissues, including the heart. Studies conducted in both GH receptor null and bovine GH transgenic mice have demonstrated specific cardiac structural and functional changes. In each of these mouse lines, however, GH-induced signaling is altered systemically, being decreased in GH receptor null mice and increased in bovine GH transgenic mice. Therefore, to clarify the direct effects GH has on cardiac tissue, we developed a tamoxifen-inducible, cardiac-specific GHR disrupted (iC-GHRKO) mouse line. Cardiac GH receptor was disrupted in 4-month-old iC-GHRKO mice to avoid developmental effects due to perinatal GHR gene disruption. Surprisingly, iC-GHRKO mice showed no difference vs controls in baseline or postdobutamine stress test echocardiography measurements, nor did iC-GHRKO mice show differences in longitudinal systolic blood pressure measurements. Interestingly, iC-GHRKO mice had decreased fat mass and improved insulin sensitivity at 6.5 months of age. By 12.5 months of age, however, iC-GHRKO mice no longer had significant decreases in fat mass and had developed glucose intolerance and insulin resistance. Furthermore, investigation via immunoblot analysis demonstrated that iC-GHRKO mice had appreciably decreased insulin stimulated Akt phosphorylation, specifically in heart and liver, but not in epididymal white adipose tissue. These changes were accompanied by a decrease in circulating IGF-1 levels in 12.5-month-old iC-GHRKO mice. These data indicate that whereas the disruption of cardiomyocyte GH-induced signaling in adult mice does not affect cardiac function, it does play a role in systemic glucose homeostasis, in part through modulation of circulating IGF-1.
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Adam
authors.initials: A
authors.lastname: Jara
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Xingbo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Don
authors.initials: D
authors.lastname: Sim
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Chance M
authors.initials: CM
authors.lastname: Benner
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Silvana
authors.initials: S
authors.lastname: Duran-Ortiz
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Edward O
authors.initials: EO
authors.lastname: List
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Darlene E
authors.initials: DE
authors.lastname: Berryman
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Edison Biotechnology Institute (A.J., X.L., D.S., C.M.B., S.D.-O., Y.Q., E.O.L., D.E.B., J.J.K.), Departments of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Department of Biological Sciences (S.D.-O., J.J.K.), School of Applied Health Sciences and Wellness (X.L., C.M.B., D.E.B.), College of Health Sciences and Professions, Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701; and Program in Molecular Medicine (J.K.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001823:Body Composition / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D007328:Insulin; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose