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.

中文翻译：

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肥胖SM / J小鼠自发恢复功能性β细胞团

维持功能性β细胞质量对于预防糖尿病至关重要，但是尚不清楚导致肥胖情况下β细胞群蓬勃发展或衰竭的生理机制。高脂喂养的SM / J小鼠随着年龄的增长自发地从高血糖转变为正常血糖，为研究β细胞适应性提供了独特的机会。在这里，我们表征了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。肥胖的SM / J小鼠在解决高血糖症时，可显着提高循环和胰腺胰岛素水平，同时改善胰岛素敏感性。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细胞的质量，而不增加了α细胞的质量。肥胖的SM / J小鼠的β细胞有丝分裂指数并未升高，而α细胞有丝分裂指数却升高。对孤立的胰岛的功能评估表明，肥胖的SM / J小鼠增加了葡萄糖刺激的胰岛素分泌，减少了基础胰岛素的分泌，并增加了胰岛胰岛素的含量。这些结果表明，高血糖的消退是β细胞质量扩张和改善的β细胞功能的基础，这表明肥胖SM / J小鼠是探索在肥胖背景下如何恢复功能性β细胞质量的宝贵工具。