Spontaneous restoration of functional β-cell mass in obese SM/J mice

Miranda, M. A.; Carson, C.; St Pierre, C. L.; Macias-Velasco, J. F.; Hughes, J. W.; Kunzmann, M.; Schmidt, H.; Wayhart, J. P.; Lawson, H. A.

doi:10.1101/2020.05.19.104588

bioRxiv · 10.1101/2020.05.19.104588

Spontaneous restoration of functional β-cell mass in obese SM/J mice

Miranda, M. A.·Carson, C.·St Pierre, C. L.·Macias-Velasco, J. F.·Hughes, J. W.·Kunzmann, M.·Schmidt, H.·Wayhart, J. P.·Lawson, H. A.

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Abstract

Maintenance of functional {beta}-cell mass is critical to preventing diabetes, but the physiological mechanisms that cause {beta}-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 {beta}-cell adaptation. Here, we characterize insulin homeostasis, islet morphology, and {beta}-cell function during SM/Js 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 {beta}-cell mass but not -cell mass. Obese SM/J mice do not show elevated {beta}-cell mitotic index, but rather elevated -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 {beta}-cell mass expansion and improved {beta}-cell function underlie the resolution of hyperglycemia, indicating that obese SM/J mice are a valuable tool for exploring how functional {beta}-cell mass can be recovered in the context of obesity.

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Miranda, M. A., Carson, C., St Pierre, C. L., Macias-Velasco, J. F., Hughes, J. W., Kunzmann, M., Schmidt, H., Wayhart, J. P., Lawson, H. A.. 2020-05-20. Spontaneous restoration of functional β-cell mass in obese SM/J mice. https://doi.org/10.1101/2020.05.19.104588

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