Insulin, IGF-1, and GH Receptors Are Altered in an Adipose Tissue Depot-Specific Manner in Male Mice With Modified GH Action.
Growth hormone (GH) is a determinant of glucose homeostasis and adipose tissue (AT) function. Using 7-month-old transgenic mice expressing the bovine growth hormone (bGH) gene and growth hormone receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression of proteins involved in the interrelated signaling pathways of GH, insulinlike growth factor 1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice. Glycated hemoglobin levels were reduced in bGH and GHR-/- mice, and bGH mice displayed impaired gluconeogenesis as judged by pyruvate tolerance testing. Serum IGF-1 was elevated by 90% in bGH mice, whereas IGF-1 and insulin were reduced by 97% and 61% in GHR-/- mice, respectively. Igf1 RNA was increased in subcutaneous, epididymal, retroperitoneal, and brown adipose tissue (BAT) depots in bGH mice (mean increase ± standard error of the mean in all five depots, 153% ± 27%) and decreased in all depots in GHR-/- mice (mean decrease, 62% ± 4%). IGF-1 receptor expression was decreased in all AT depots of bGH mice (mean decrease, 49% ± 6%) and increased in all AT depots of GHR-/- mice (mean increase, 94% ± 8%). Insulin receptor expression was reduced in retroperitoneal, mesenteric, and BAT depots in bGH mice (mean decrease in all depots, 56% ± 4%) and augmented in subcutaneous, retroperitoneal, mesenteric, and BAT depots in GHR-/- mice (mean increase: 51% ± 1%). Collectively, our findings indicate a role for GH in influencing hormone signaling in AT in a depot-dependent manner.
Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, 8000 Aarhus, Denmark.|Danish Diabetes Academy, 5000 Odense, Denmark.|Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701.
Rikke
R
Hjortebjerg
Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701.|Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.|The Diabetes Institute at Ohio University, Ohio University, Athens, Ohio 45701.
Darlene E
DE
Berryman
Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701.|The Diabetes Institute at Ohio University, Ohio University, Athens, Ohio 45701.
Ross
R
Comisford
Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama 35924.|Medical Service, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Stuart J
SJ
Frank
Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701.
Edward O
EO
List
Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, 8000 Aarhus, Denmark.
Mette
M
Bjerre
Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, 8000 Aarhus, Denmark.|Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
Jan
J
Frystyk
Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701.|Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
John J
JJ
Kopchick
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D007328:Insulin; D011986:Receptors, Somatotropin; C073294:growth hormone, bovine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone