Figure 1.

Dynamic insulin secretion in response to nutrients in mature and immature islet cells. (A) Schematic representation of experimental design. (B) Representative heat map of metabolite abundance in serum of embryos, neonates and adult mice. Experiment was repeated twice using embryonic samples (n=4), neonates (n=32) and adults (n=6). (C) A relative ratio of amino acids and their metabolites (left graph) and glucose (right graph) in the serum of mice of indicated age. Data points represent mean ± SEM. P-values, * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001, unpaired Student’s t test. (D-G) Fold insulin levels secreted by mature mouse (n=6) and human islets (D and F, respectively) and fetal mouse (E18, n=6) and human islets (E and G, respectively) in a dynamic perfusion assay in low glucose (2.8 mM), low glucose and physiological levels of amino acids, high glucose (16.7 mM) and KCl (30mM). The fetal and adult human data is representative from single donors using 6 technical replicates and repeated in three independent experiments. Data points represent mean ± SEM. (H) Fold insulin levels secreted by islets from neonatal mice (P5, n=6) in a dynamic perfusion assay. Secreted insulin levels were normalized to basal insulin secretion of each sample. (I) Fold insulin levels secreted by fetal human islets that were cultured in vitro in a fetal-like medium (blue, 5.5mM glucose and high amino acid levels) and mature-like medium (green, 5.5mM glucose and low amino acid levels). The result was repeated in three independent experiments.