Supplementary Figure 4: Expression of CELA2A in disease states from Gene Expression Omnibus (GEO) datasets and insulin, glucose and glucagon levels before and after the meal in human subjects.

a, Relative expression of CELA2A mRNA in vastus lateralis muscle samples from insulin-resistant obese (n = 5) and insulin sensitive (n = 5) Pima Indians. b, Beta-cell enriched pancreatic tissues obtained from subjects with T2D (n = 10) and without T2D (n = 10), shown as dot plots (mean ± s.e.m). Data were derived from GEO database (see the references in the text). Statistical analyses were carried out using two-sided Student’s t-test; P = 0.0115 and P = 0.0150, respectively. c, Glucagon level (pg/dl; mean ± s.e.m) in p.D121N-CELA2A carriers compared to controls (n = 7 control samples vs. 8 p.D121N-carriers). Statistical analyses were carried out using two-sided Student’s t-test, P = 0.033. d,e, Plasma glucagon levels (pg/dl; mean ± s.e.m) in fast/fed healthy individuals and correlation with plasma CELA2A in healthy subjects before and after meal (n = 8 samples). Statistical analyses were carried out using two-sided Student’s t-test; P = 0.049. Correlation coefficient (r2 = -0.72) for e was performed using GraphPad. f, CELA2A to glucose ratios (mean ± s.e.m) at 60 min hyperglycemic clamp and OGTT represented as bar chart (n = 5 samples, Student’s t-test, two-sided, P = n.s.). g,h, Average values of CELA2A and glucagon (pg/dl; mean ± s.e.m) during hyperglycemic clamp and OGTT studies (n = 5 samples). OGTT, oral glucose tolerance test. AU, arbitrary units. All human studies were performed only once.