Fig. 7: Functional follow-up of T2D-associated DEGs in human alpha and beta cells.
a,b, Volcano plots showing T2D-associated DEGs in human alpha (a) and beta (b) cells, P < 0.05 based on DESeq2 (ref. 82). c, mRNA expression of T2D-associated beta cell DEGs selected for functional follow-up based on q < 0.1 and DESeq2 (ref. 82). Data from 15 non-diabetic donors and 7 donors with T2D. Women and men are represented by filled and open circles, respectively. Data are presented as the mean ± s.e.m. d, siRNA-mediated knockdown of ADCY9, FBLL1 and ZSWIM9 in human islets from five donors. e, Silencing of Adcy9, Fbll1 and Zswim9 using siRNA in rat INS-1 832/13 beta cells. n = 4 (Fbll1) or 6 (Adcy9 and Zswim9) biological replicates. f, Insulin secretion from human islets stimulated with 1 mM and 20 mM glucose. Measurements were performed on islets from the same five donors as in d. Data are presented as the mean ± s.e.m. g, Insulin secretion from INS-1 832/13 beta cells during 1 h of stimulation with low (2.8 mM) or high (16.7 mM) glucose. n = 6 biological replicates. h, Depolarization-induced insulin secretion (35 mM K+) from INS-1 832/13 beta cells. n = 6 biological replicates from the same experiments as e. i, Overexpression of GNAL (OE-GNAL), ONECUT2 (OE-ONECUT2), SNX1 (OE-SNX1) or TRAPPC13 (OE-TRAPPC13) in human islets from five (SNX1) or six (GNAL, ONECUT2 and TRAPPC13) donors. j, OE-GNAL, OE-ONECUT2, OE-SNX1 and OE-TRAPPC13 in INS-1 832/13 beta cells. n = 5 (ONECUT2) or 6 (GNAL, SNX1 and TRAPPC13) biological replicates. k, Insulin secretion from human islets stimulated with 1 mM or 20 mM glucose for 1 h. Measurements were performed on islets from the same donors as in i. l,m, Insulin secretion from INS-1 832/13 beta cells during 1 h of stimulation with 2.8 mM or 16.7 mM glucose in absolute values (l) and as fold change, that is, secretion at 16.7 mM divided by secretion at 2.8 mM glucose (m). n = 6 biological replicates. n, Depolarization-induced insulin secretion by stimulation with 35 mM K+ in INS-1 832/13 beta cells. n = 3 biological replicates. In d–n, data are presented as the mean ± s.e.m. and *P < 0.05, **P < 0.01, ***P < 0.001 versus siNC or GFP, based on two-tailed (d–n) paired Student’s t-tests. The same colour represents paired samples included in the same experiment, for human islets from the same donor and for the INS-1 832/13 beta cells from the same cell passage. The q values for b,c were corrected for multiple testing, while the other P values throughout were not.
