Figure 2.

Exposure to HFDs Does Not Affect the Function of hESC-Derived Pancreatic Endocrine Cells In Vivo

The development of hESC-derived progenitor cells into pancreatic endocrine cells was assessed in mice fed a 10% fat (black), 45% or 60% fat (purple), or Western (green) diet. See Figure S2 for characterization of the progenitor cells pre-transplantation.

(A) Human C-peptide levels were measured after an overnight fast and 40 min following an oral mixed-meal challenge (“fed”) at 8, 12, 16, and 20 weeks post-transplantation. ^∗p < 0.05, paired t test (fast versus fed).

(B and C) At 18 weeks post-transplantation, human C-peptide levels were measured during an i.p. glucose tolerance test (ipGTT). In (B) data are normalized to baseline levels, and in (C) raw levels (ng/ml) are presented for individual animals, with each diet group shown on a separate plot. ^∗p < 0.05, one-way repeated-measures ANOVA (versus time 0).

(D–F) At 24 weeks post-transplantation, an i.p. arginine tolerance test (ipArgTT) was performed. Plasma was collected after a 4-hr fast and 15 min following arginine administration to measure human insulin (D) and glucagon (E and F) levels. (E) shows glucagon levels at 0 and 15 minutes in transplant recipients, and (F) shows glucagon levels in sham-treated mice (Sham, striped bars) and transplant recipients (Tx, solid bars) at 15 minutes only. The red line indicates the lower limit of detection for the glucagon assay. (D and E) ^∗p < 0.05, one-tailed paired t test (0 versus 15 min); (F) ^∗p < 0.05, two-tailed t test (sham versus Tx). Data points from individual mice are shown as box-and-whisker plots.

See also Table S2.