Department of Genetics, Washington University School of Medicine, Saint Louis, MO, USA.
Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
Physiol Rep. 2020 Oct;8(20):e14573. doi: 10.14814/phy2.14573.
Maintenance of functional β-cell mass is critical to preventing diabetes, but the physiological mechanisms that cause β-cell populations to thrive or fail in the context of obesity are unknown. High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we characterize insulin homeostasis, islet morphology, and β-cell function during SM/J's diabetic remission. As they resolve hyperglycemia, obese SM/J mice dramatically increase circulating and pancreatic insulin levels while improving insulin sensitivity. Immunostaining of pancreatic sections reveals that obese SM/J mice selectively increase β-cell mass but not α-cell mass. Obese SM/J mice do not show elevated β-cell mitotic index, but rather elevated α-cell mitotic index. Functional assessment of isolated islets reveals that obese SM/J mice increase glucose-stimulated insulin secretion, decrease basal insulin secretion, and increase islet insulin content. These results establish that β-cell mass expansion and improved β-cell function underlie the resolution of hyperglycemia, indicating that obese SM/J mice are a valuable tool for exploring how functional β-cell mass can be recovered in the context of obesity.
维持功能性β细胞群体对于预防糖尿病至关重要，但在肥胖背景下导致β细胞群体繁荣或衰竭的生理机制尚不清楚。高脂肪喂养的 SM/J 小鼠会随着年龄的增长自发地从高血糖肥胖转变为正常血糖肥胖，这为研究β细胞适应性提供了独特的机会。在这里，我们描述了 SM/J 糖尿病缓解期间的胰岛素稳态、胰岛形态和β细胞功能。随着它们解决高血糖问题，肥胖的 SM/J 小鼠会显著增加循环和胰腺中的胰岛素水平，同时提高胰岛素敏感性。对胰腺切片的免疫染色显示，肥胖的 SM/J 小鼠选择性地增加了β细胞质量，而不是α细胞质量。肥胖的 SM/J 小鼠没有表现出升高的β细胞有丝分裂指数，而是升高的α细胞有丝分裂指数。对分离胰岛的功能评估显示，肥胖的 SM/J 小鼠增加了葡萄糖刺激的胰岛素分泌，减少了基础胰岛素分泌，并增加了胰岛胰岛素含量。这些结果表明，β细胞质量的扩张和β细胞功能的改善是高血糖缓解的基础，这表明肥胖的 SM/J 小鼠是探索肥胖背景下功能性β细胞群体如何恢复的有价值的工具。
