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 andGHR(-/-) mice, and bGHmice 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 bGHmice (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% 6 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% +/- 6 1%). Collectively, our findings indicate a role for GH in influencing hormone signaling in AT in a depot-dependent manner.