%0 Journal Article %A Mario A Miranda %A Caryn Carson %A Celine L St Pierre %A Juan F Macias-Velasco %A Jing W Hughes %A Marcus Kunzmann %A Heather Schmidt %A Jessica P Wayhart %A Heather A Lawson %T Spontaneous restoration of functional β-cell mass in obese SM/J mice %D 2020 %R 10.1101/2020.05.19.104588 %J bioRxiv %P 2020.05.19.104588 %X 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.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2020/05/20/2020.05.19.104588.full.pdf