1. Supplementary table 1 Clinical data of the female patients with and without diabetes (n) DiabetesNon-diabetes p value 58.6 ± 8.5 (3)54.3 ± 4.1 (3) 5.49 ± 0.23 (3)7.33 ± 0.37 (3) Female Age (years) FPG (mM) <0.05 >0.05

2. Supplementary Fig. 1 0 10 20 30 40 Cont (n=5) STZ (n=5) Body weight (g) (Day) 0 10 20 30 40 (Day) Cont (n=5) STZ (n=5) 0153045607590 0153045607590 Blood glucose (mM) * * *** * * * * * *

3. Normal Diabetes Supplementary Fig. 2A A 100 μm200 μm100 μm200 μm Nrf2 Insulin Merged Human (male)

4. Supplementary Fig. 2B 200 μm 100 μm NormalDiabetes 200 μm 100 μm Human (female) B

5. 100 μm Normal Diabetes C Mouse (male) Nrf2 Insulin Merged 200 μm100 μm200 μm Supplementary Fig. 2C

6. 0 20 40 60 80 NQO1 positive cells (%) * * * p<0.05 H 2 O 2 Dh404     50  m ControlDh404 H2O2H2O2 H 2 O 2 + dh404 Supplementary Fig. 3 NQO-1

7. p62 β-actin LC3-II Ub-proteins p62 β-actin LC3-II Ub-proteins 170 130 100 70 55 40 35 25 15 170 130 100 70 55 40 35 25 15 Soluble Insoluble FBS H 2 O 2  0h0h1h1h6h6h12h24h         FBS H 2 O 2  0h0h1h1h6h6h12h24h         p62 β-actin LC3-II p62 LC3-II β-actin Ub-proteins 170 130 100 70 55 40 35 25 15 170 130 100 70 55 40 35 25 15 Dh404   Soluble Insoluble Ub-proteins A B Supplementary Fig. 4 kDa 14 62 43 kDa 14 62 43 14 62 43 14 62 43

8. Supplementary Fig. 5 50 µm 100 µm 250 µm 50 µm 100 µm 250 µm Dithizone staining A Glucose 0 5 10 15 20 25 2.8 mM25 mM Insulin release (mU/IEQ) * 100 µm 50 µm 100 µm 50 µm B C   Anti-insulin & proinsulinAnti-glucagon