Insulin, IGF-1, and GH Receptors Are Altered in an Adipose Tissue Depot-Specific Manner in Male Mice With Modified GH Action

Endocrinology. 2017 May 1;158(5):1406-1418. doi: 10.1210/en.2017-00084.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism*
  • Animals
  • Cattle
  • Gene Expression Regulation / drug effects
  • Growth Hormone / pharmacology*
  • Insulin / genetics*
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Specificity / drug effects
  • Organ Specificity / genetics
  • Receptors, Somatotropin / genetics*
  • Receptors, Somatotropin / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Insulin
  • Receptors, Somatotropin
  • growth hormone, bovine
  • Insulin-Like Growth Factor I
  • Growth Hormone