Fig. 5: Obese prediabetic mice given a recombinant REG3A protein showed improved glucose homeostasis and increased glucose uptake by skeletal muscle.

After 10 weeks of HFD (4655 kcal/kg), WT mice received 43 µg per day of a recombinant REG3A protein (rcREG3A) subcutaneously for 28 days (n = 9). Mice on a standard diet (chow, CTD) also received rcREG3A for the same period (n = 5). HFD-fed (n = 10) and CTD-fed control mice (n = 5) received an equivalent volume of buffer (vehicle). a Diagram of the experimental protocol. OGTT: oral glucose tolerance test. ITT: insulin tolerance test. b–k Measurement of indicated markers at the end of rcREG3A or buffer treatment. b Body weight over time. c Body fat and lean mass. d Histological score of liver steatosis. e Serum levels of lipids. f Serum levels of leptin. g Fasting blood glucose. h Blood glucose curves under oral glucose tolerance tests OGTT. Right: area under the curve of OGTT. i blood insulin concentrations during glucose tolerance test. j Blood glucose curves during insulin tolerance test. Right: area under the curve of ITT. k Hyperinsulinemic-euglycemic clamp in mice fed a chow (CTD, n = 10) or a high-fat (HFD, n = 14) diet and treated subcutaneously with 43 µg per day of a recombinant REG3A protein (rcREG3A) or an equivalent volume of buffer for 28 days. GUR: Whole-body glucose utilization rate. GIR: glucose infusion rate; EGP: endogenous glucose production. l Tissue sensitivity to insulin estimated by the quantification of glucose uptake in the indicated tissues. Data are averages ± SEM. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.005 by Anova test (c, e, f, g, right h, i, k, l) or one-way repeated measures Anova (left h, left j) both followed by post-hoc test, Wilcoxon rank sum test (right j). NS or no statistical indication, no significance.