Fig. 3: Ketogenic diet suppresses pancreatic islet cell proliferation.

A, B Body weights (A) and blood glucose levels (B) of 45-week-old Men1^f/f-RipCre⁺ mice fed a normal diet (N = 18) or ketogenic diet (N = 32). Mice were fed ad libitum. Data are represented as the mean ± SEM. C, D. Blood glucose levels (C) and serum insulin levels (D) of 20-week-old Men1^f/f-RipCre⁺ mice fed a normal diet (N = 4) or ketogenic diet from 10 weeks of age (N = 3). Fasted mice (mice fasted overnight to 41 h) and mice refed the usual meal for 1.5 h were analyzed. Data are represented as the mean ± SEM. E–H. Mice were treated as in (C), and pancreatic sections of mice refed a normal diet or ketogenic diet were stained with HE, anti-P-S6 (E), and anti-P-mTOR (F). High-magnification images are shown in the bottom panels. Relative intensities of P-S6 staining from 5 islets from 1 mouse fed a normal diet and 4 islets from 2 mice fed a ketogenic diet were calculated and shown in graph G. Relative intensities of P-mTOR staining from 4 islets derived from 2 mice fed a normal diet, and 2 mice fed a ketogenic diet were calculated and shown in graph H. In G and H, data are represented as the mean ± SD. I–K Pancreatic sections of 30-week-old Men1^f/f-RipCre⁺ mice fed a normal diet or ketogenic diet from 10 weeks of age were stained with HE, anti-Ki67, and anti-p27 (I). In J, K, 4 islets derived from 2 mice fed a normal diet and 2 mice fed a ketogenic diet were analyzed. Total and Ki67 positive nuclei numbers were counted, and the percentage of Ki67 positive cells was calculated and shown in graph J. Relative intensities of p27 staining were calculated and shown in graph K. In J, K, data are represented as the mean ± SD.