Fig. 6: Hepatic Kmt5c loss mitigates diabetic hyperglycemia.

a Five-week-old db/db mice were injected with adenoviruses encoding murine Kmt5c shRNA via the tail vein. Two weeks later, blood glucose levels were measured underfed (n = 6 in each group, male) and 16 h fasting conditions (n = 6 each group, male). b, c PTT (b) (n = 6 per group, male) and GcTT (c) (n = 6 each group, male) were performed in the mice treated as in (a). d Representative western blot analysis (left) and protein quantifications (right) in the indicated mice after 16 h fasting (n = 6 for each group, male mice). e–g GTT (e) (db/db+Scr, n = 6; db/db+shKmt5c, n = 7, male) and ITT (g) (n = 6 each group, male) were performed in the mice described in (a). The quantification of GTT was shown in (f). h Five-week-old WT and KO male mice were fed a high-fat diet for 12 weeks. Blood glucose levels were then measured under fed conditions (n = 7 in each group, male mice) and after 24-hour fasting (n = 7 in each group, male mice). i–l PTT (i), GcTT (j), GTT (k), and ITT (l) assay were performed in the mice of (h) (n = 7 each group, male mice). m Pearson correlation analysis for normalized Kmt5c mRNA levels versus fasting plasma glucose levels in human subjects (n = 19). n, o Relative Kmt5c mRNA level (n) (Non-T2DM, n = 11; T2DM, n = 8) and representative KMT5C protein level (o) (Non-T2DM, n = 6; T2DM, n = 7) in the human liver specimens. a–o data present mean ± s.e.m; n represent biologically independent animal/human samples. a–l, n, o two-tailed unpaired Student’s t test. m Pearson correlation analysis. Experiments in (a–l) were repeated independently three times with similar results. Source data are provided as a Source Data file.