In the endocrine pancreas, growth hormone (GH) is known to promote pancreatic islet growth and insulin secretion. In this study, we show that GH receptor (GHR) loss in the germline and in adulthood impacts islet mass in general but more profoundly in male mice. GHR knockout (GHRKO) mice have enhanced insulin sensitivity and low circulating insulin. We show that the total cross-sectional area of isolated islets (estimated islet mass) was reduced by 72% in male but by only 29% in female GHRKO mice compared to wild type controls. Also, islets from GHRKO mice secreted ~50% less glucose-stimulated insulin compared to size-matched islets from wild type mice. We next used mice with a floxed Ghr gene to knock down the GHR in adult mice at six-months of age (6mGHRKO) and examined the impact on glucose and islet metabolism. By 12-months of age, female 6mGHRKO mice had increased body fat and reduced islet mass but had no change in glucose tolerance or insulin sensitivity. However, male 6mGHRKO mice had nearly twice as much body fat, substantially reduced islet mass, and enhanced insulin sensitivity, but no change in glucose tolerance. Despite large losses in islet mass, glucose-stimulated insulin secretion from isolated islets was not significantly different between male 6mGHRKO and controls while isolated islets from female 6mGHRKO mice showed increased glucose-stimulated insulin release. Our findings demonstrate the importance of GH to islet mass throughout life and that unique sex-specific adaptations to the loss of GH signaling allow mice to maintain normal glucose metabolism.

中文翻译：

---

小鼠生殖系或成年期生长激素信号传导的丧失会减少胰岛质量并改变胰岛功能，并具有显着的性别差异

在内分泌胰腺中，已知生长激素 (GH) 可促进胰岛生长和胰岛素分泌。在这项研究中，我们表明，生殖系和成年期的 GH 受体 (GHR) 缺失会影响胰岛质量，但对雄性小鼠的影响更为深远。GHR 敲除 (GHRKO) 小鼠具有增强的胰岛素敏感性和低循环胰岛素。我们表明，与野生型对照相比，雄性 GHRKO 小鼠的孤立胰岛的总横截面积（估计的胰岛质量）减少了 72%，而雌性 GHRKO 小鼠仅减少了 29%。此外，与来自野生型小鼠的大小匹配的胰岛相比，来自 GHRKO 小鼠的胰岛分泌的葡萄糖刺激的胰岛素减少了约 50%。接下来，我们使用具有 floxed Ghr 基因的小鼠在 6 个月大的成年小鼠 (6mGHRKO) 中敲除 GHR，并检查了对葡萄糖和胰岛代谢的影响。到 12 个月大时，雌性 6mGHRKO 小鼠的体脂增加，胰岛质量减少，但葡萄糖耐量或胰岛素敏感性没有变化。然而，雄性 6mGHRKO 小鼠的体脂几乎增加了一倍，胰岛质量显着降低，胰岛素敏感性增强，但葡萄糖耐量没有变化。尽管胰岛质量大幅下降，但雄性 6mGHRKO 和对照组之间分离的胰岛的葡萄糖刺激胰岛素分泌没有显着差异，而雌性 6mGHRKO 小鼠的分离胰岛显示葡萄糖刺激的胰岛素释放增加。我们的研究结果证明了 GH 对整个生命过程中胰岛质量的重要性，以及对 GH 信号丢失的独特性别特异性适应使小鼠能够维持正常的葡萄糖代谢。