Figure legends Supplemental Fig.1. Glucose-induced insulin secretion and insulin content of islets. Supplemental Fig. 2.

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Figure legends Supplemental Fig.. Glucose-induced insulin secretion and insulin content of islets. Insulin secretory responses to.,., and. mm glucose (A) (n = 7-), and the insulin content in the islets determined after acid ethanol extraction (B) (n = ). *P <.5; **P <.. Values are the means ± SE. White bars, ; black bars,. Supplemental Fig.. Beta cell mass growth during days postsurgery in WT mice and WT mice. Beta cell mass (n = 5). The black line superimposed on the bars represents the theoretical beta cell mass postsurgery. Values are the means ± SE. White bars, ; black bars,. Supplemental Fig.. BrdU- and insulin-positive cells in islet and BrdU-positive cells in acinar. Representative histology of endocrine pancreas staining with BrdU and insulin antibody in WT and IRS- -/- mice (A), and in WT and Gck +/- mice (B) on postoperative day. The panels with red frame show high magnification images of BrdU- and insulinpositive cells in islets after a pancreatectomy. The panels with black flame show high magnification images of BrdU-positive cells in acinar cells after a pancreatectomy. Supplemental Fig.. The expression of phospho-histone H in the islets from WT and IRS- -/- mice after a pancreatectomy on postoperative days and. Estimation of phospho-histone H positive β cells on postoperative days and (n = 5). Values are the means ± SE. White bars, ; black bars,. Supplemental Fig. 5. No significant change was observed in islet neogenesis in WT and IRS- -/- mice after a pancreatectomy. The percentage of small insulin + cell clusters (<5 μm ) to total islet number was estimated on postoperative day (n = 5). Values are the means ± SE. White bars, more than 5 μm β cell population; black bars, less than 5 μm β cell population. Supplemental Fig.. Changes in gene expression levels in the islets from WT and IRS- -/- mice after a pancreatectomy on postoperative day. Each expression level was quantified (n = -5). *P <.5; **P <.. Values are the means ± SE. White bars, ; black bars,. Supplemental Fig. 7. Gck +/- mice developed diabetes after a % partial pancreatectomy. (A and B) Body weight gain (A) and Casual blood glucose levels (B) in WT and Gck +/- mice after surgery (n=). *P <.5 vs. Gck +/- ; **P < vs.. Gck +/- ; P <.5 vs. WT; P <. vs. WT. (C and D) Glucose tolerance in WT and Gck +/- mice on postoperative day. Blood glucose levels (C) and serum insulin levels (D) (n = 7-). (E) Casual blood glucose levels and serum insulin levels on postoperative day (n = ). (F and G) Insulin tolerance in WT and Gck +/- mice on

postoperative day 7 (n = 5-). Blood glucose levels and AUC (F). Glucose value is calculated as a ratio of baseline glucose value (G). **P <. vs. Gck +/- ; P <.5 vs. WT. Values are the means ± SE. Open circles, WT; closed circles, WT; open square, Gck +/- ; closed square, Gck +/- ; white bars, ; black bars,. Supplemental Fig.. Changes in gene expression levels in the islets from WT and Gck +/- mice after a pancreatectomy on postoperative day. Each expression level was quantified (n = -). *P <.5; **P <.. Values are the means ± SE. White bars, ; black bars,.

Supplemental Fig. A WT IRS- -/- WT IRS- -/- WT IRS- -/- Insulin (ng/ islets). mm. mm. mm B * Insulin content (ng/ islets) ** WT IRS- -/-

Supplemental Fig. β-cell mass (mg).5.5 d d d Days post-

Supplemental Fig. A WT IRS- -/- B WT Gck +/-

Supplemental Fig. phospho-histone H-positive β-cell (%) WT IRS- -/- day WT IRS- -/- day

Supplemental Fig. 5 Number % of the total islet 75 5 5 5 μm < 5 μm WT IRS- -/-

Supplemental Fig..5.5 PDX WT IRS- -/- FoxM AurkB WT IRS- -/- WT IRS- -/- survivin WT IRS- -/- Cyclin A WT IRS- -/- Cyclin B Cyclin B Cyclin D Cyclin D Cyclin D 5 5 WT IRS- -/- WT IRS- -/-.5.5 WT IRS- -/-.5.5.5.5 WT IRS- -/- WT IRS- -/- Cyclin E Cyclin E p p p p=.9 p=.7 p=. WT IRS- -/- WT IRS- -/- WT IRS- -/- WT IRS- -/- WT IRS- -/- p7 Ezh IRS- INS INS.5.5 WT IRS- -/- WT IRS- -/- WT IRS- -/-.5.5 WT IRS- -/-.5.5 WT IRS- -/-

Supplemental Fig. 7 A B Body weight (g) WT WT Gck +/- Gck +/- d d d d9 d d Blood glucose (mg/dl) d d d d9 d d Days post- Days post- C D Blood glucose (mg/dl) 5 Insulin (ng/ml) 5 5 Time (minutes) Time (minutes) E Blood glucose (mg/dl) 5 Insulin (ng/ml) F Blood glucose (mg/dl) AUC[ (mg/l) h] 5 9 Time (minutes)

Supplemental Fig. Glucokinase.5.5.5.5 IRS-.5.5 PDX FoxM 7 5 AurkB survivin Cyclin A Cyclin B Cyclin B Cyclin D.5.5.5.5 Cyclin D.5.5 Cyclin D Cyclin E Cyclin E p p=. p=..5.5 p=.7 p p p7.5.5.5.5.5