SUPPLEMENTARY DATA Supplementary Table 1. Blood ... - Diabetes

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67.2 ± 6.5 140.2 ± 15.4 * 137.7 ± 13.8 *. His-containing dipeptides. 56.8 ± 4.5 253.7 ± 22.5 * 71.8 ± 4.5 * †. * vs. control (p < 0.05); † vs. protein extract (p < 0.05).
SUPPLEMENTARY DATA Supplementary Table 1. Blood glucose levels 90–120 min after starting insulin administration in clamp tests. Clamp tests in Fig. 2B Blood glucose (mg/dl) (n=7-9) Ave ± SEM Min Max 106.9 ± 0.5 101 112 veh 106.9 ± 0.5 102 112 His Clamp tests in Fig. 2G Blood glucose (mg/dl) (n=5) Ave ± SEM Min Max 106.3 ± 0.5 101 109 veh 107.3 ± 0.4 104 112 His Clamp tests in Fig. 3D Blood glucose (mg/dl) (n=6) Ave ± SEM Min Max 107.5 ± 0.8 101 112 Con - veh LST3KO - veh 106.0 ± 0.4 101 109 107.0 ± 0.6 102 111 Con - His LST3KO - His 107.2 ± 0.7 102 112 Clamp tests in Fig. 4F Blood glucose (mg/dl) (n=6) Ave ± SEM Min Max 107.1 ± 0.5 101 112 veh His 106.9 ± 0.5 100 112 His-CLD 107.4 ± 0.6 102 112 Clamp tests in Fig. 5H Blood glucose (mg/dl) (n=6) Ave ± SEM Min Max 106.9 ± 0.8 100 112 veh PL(icv) - veh 105.1 ± 0.7 102 109 His 107.3 ± 0.8 102 111 PL(icv) - His 106.3 ± 0.7 100 112 Clamp tests in Fig. 6E Blood glucose (mg/dl) (n=6) Ave ± SEM Min Max 105.8 ± 0.7 100 112 aCSF(icv) 107.4 ± 0.9 100 112 His(icv) Clamp tests in Fig. 7B Blood glucose (mg/dl) (n=6) Ave ± SEM Min Max Ins(icv) 107.8 ± 0.5 104 111 His+Ins(icv) 106.4 ± 0.5 103 110 Data are represented as mean ± SE values. Min and Max are respectively the minimum and maximum blood glucose levels 90–120 min after starting insulin administration in the clamp tests.

©2013 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-1701/-/DC1

SUPPLEMENTARY DATA Supplementary Table 2. Plasma amino acid levels at 30 min after protein ingestion. Low-His protein Control Protein extract Amino acid (nmol/mL) extract (n = 4) (n = 4) (n = 4) Aspartic acid 3.6 ± 0.2 4.9 ± 0.4 5.6 ± 0.3 Hydroxyproline 0.0 ± 0.0 40.1 ± 6.0 * 36.8 ± 2.0 * Threonine 102.4 ± 5.1 170.8 ± 12.1 * 170.0 ± 14.7 * Serine 70.4 ± 4.8 114.0 ± 7.9 * 101.2 ± 9.6 Asparagine 29.1 ± 2.4 37.1 ± 4.6 29.5 ± 2.7 Glutamic acid 31.9 ± 1.4 35.5 ± 2.8 46.4 ± 2.9 * Glutamine 388.6 ± 29.2 439.2 ± 20.4 418.1 ± 25.4 Proline 46.1 ± 3.0 121.4 ± 11.3 * 100.1 ± 7.6 * Glycine 166.1 ± 4.0 320.6 ± 14.2 * 396.6 ± 11.0 * † Alanine 191.8 ± 8.5 370.5 ± 52.9 * 282.8 ± 24.9 Valine 196.7 ± 12.5 343.2 ± 13.9 * 315.5 ± 5.0 * Cysteine 1.5 ± 1.0 0.7 ± 0.7 4.5 ± 2.3 Methionine 33.2 ± 3.5 65.4 ± 5.0 * 73.0 ± 7.1 * Isoleucine 105.6 ± 7.4 179.5 ± 6.1 * 167.0 ± 0.6 * Leucine 174.1 ± 15.4 338.8 ± 11.7 * 367.8 ± 6.0 * Tyrosine 43.1 ± 2.8 71.4 ± 3.1 * 76.4 ± 9.7 * Phenylalanine 64.8 ± 3.5 86.2 ± 2.5 82.7 ± 3.8 Histidine 45.9 ± 3.5 61.8 ± 2.1 * 52.2 ± 3.3 3-Methylhistidine 10.9 ± 1.0 11.9 ± 0.6 15.0 ± 1.1 * 1-Methylhistidine 0.0 ± 0.0 5.6 ± 1.5 * 4.6 ± 0.1 Carnosine 0.0 ± 0.0 55.3 ± 8.5 * 0.0 ± 0.0 † Anserine 0.0 ± 0.0 119.1 ± 9.8 * 0.0 ± 0.0 † Tryptophan 40.8 ± 3.7 46.8 ± 3.5 33.2 ± 0.5 Hydroxylysine 0.0 ± 0.0 15.7 ± 3.6 * 11.0 ± 0.7 Ornithine 41.2 ± 1.6 154.6 ± 13.8 * 132.9 ± 17.4 * Lysine 150.5 ± 10.1 375.1 ± 26.4 * 416.6 ± 51.6 * Arginine 67.2 ± 6.5 140.2 ± 15.4 * 137.7 ± 13.8 * His-containing dipeptides 56.8 ± 4.5 253.7 ± 22.5 * 71.8 ± 4.5 * † * vs. control (p < 0.05); † vs. protein extract (p < 0.05) Low-His protein extract: low-histidine protein extract His-containing dipeptide: histidine + 3-methylhistidine + 1-methylhistidine + carnosine + anserine

©2013 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-1701/-/DC1

SUPPLEMENTARY DATA Supplementary Table 3. Plasma histidine levels after protein ingestion or histidine injection. After 30 min After 120 min Amino acid Control Protein extract His-ip Protein extract His-ip (nmol/mL) (n = 4) (n = 4) (n = 4) (n = 4) (n = 4) Histidine 42.5 ± 1.2 65.4 ± 1.7 * 69.5 ± 2.4 * 57.4 ± 2.3 * 51.4 ± 2.9 * * vs. control (p < 0.05) ip: intraperitoneal Supplementary Figure 1. Plasma insulin levels at 120 min after starting insulin infusion during hyperinsulinemic clamp tests.

Data are represented as mean ± SE (n=6-7) values. * vs. control (p < 0.05)

©2013 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-1701/-/DC1