Figure 2. Glucose and insulin levels, islet mass and glucose and insulin tolerance.

Mice were fasted for 18 h overnight and then refed or left to fast until sacrifice 6 h later. Circulating levels of (a) glucose (IR floxed, N = 17 fasting, N = 17 refed; LIRKO, N = 17 fasting, 18 refed; IR/FoxO1 floxed, N = 16 fasting, 20 refed; LIRFKO, N = 16 fasting, 20 refed) and (b) insulin (IR floxed, N = 5 fasting, 6 refed; LIRKO, N = 6 fasting, 6 refed; IR/FoxO1 floxed, N = 4 fasting, 4 refed; LIRFKO, N = 5 fasting, 4 refed) are shown. (c) C-peptide. Serum levels of C-peptide were measured in refed IR floxed (N = 6), LIRKO (N = 6), IR/FoxO1 floxed (N = 6) and LIRFKO (N = 4) mice. (d) C-peptide/insulin ratio. The ratio of C-peptide to insulin was calculated to evaluate effects on insulin clearance in IR floxed (N = 6), LIRKO (N = 6), IR/FoxO1 floxed (N = 4) and LIRFKO (N = 5) mice. (e) Islet mass. Islet and total pancreatic cross-sectional area were determined in scanned images and islet area expressed relative to total pancreatic area is shown for IR floxed (N = 6), LIRKO (N = 6), IR/FoxO1 floxed (N = 6) and LIRFKO (N = 6) mice. (f) Glucose tolerance. IR floxed (solid circle, solid line, N = 6), LIRKO (open circle, dashed line, N = 5), IR/FoxO1 floxed (solid triangle, solid line, N = 4) and LIRFKO (open triangle, dot-dash line, N = 5) mice were fasted 18 h overnight and glucose levels in tail blood were measured at baseline and 15, 30, 60 and 90 min after treatment with dextrose (2 g kg⁻¹ i.p.). (g) Insulin tolerance. IR floxed (solid circle, solid line, N = 6), LIRKO (open circle, dashed line, N = 5), IR/FoxO1 floxed (solid triangle, solid line, N = 8) and LIRFKO (open triangle, dot-dash line, N = 7) were fasted for 3 h and glucose levels were measured at baseline and 15, 30, 60 and 90 min after treatment with insulin (1Ukg⁻¹ i.p.). (h) Glucose tolerance w/wo S961 treatment. Overnight fasted IR/FoxO1 floxed and LIRFKO mice (N = 5–7 per group) were treated with S961 in PBS or PBS alone 30 min prior to treatment with dextrose (2 g kg⁻¹ i.p.; t = 0). (i) Insulin tolerance w/wo S961 treatment. IR/FoxO1 floxed and LIRFKO mice (N = 5–7 per group) were fasted for 3 h then treated with S961 30 min before treatment with insulin (t = 0). Results are presented as the mean and s.e.m. in each figure, and statistical significance (*P<0.05 versus IR floxed control, and ^@P<0.05 LIRFKO versus IRF floxed mice) was determined by one-way analysis of variance and Fisher’s post-hoc test.