Figure 2

Development of diabetes mellitus in Wfs1-ex5-KO232 rats. (a) Wfs1-ex5-KO232 animals are slightly lighter than wild-type (WT) rats of similar ages and begin to lose weight after 10 months of age. (b) Basal blood glucose levels were similar for both genotypes up to 11 months of age; thereafter, Wfs1-ex5-KO232 rats develop hyperglycaemia. (c) Wfs1-ex5-KO232 rats developed glycosuria after 10 months of age. (d) Insulin levels were lower in older Wfs1-ex5-KO232 animals compared to levels in WT animals of the same age. For the insulin tolerance tests (ITTs), human insulin was administered (1 U/kg, s.c.), and blood glucose levels were measured at the indicated time points. There were no genotype-associated changes in insulin sensitivity in either (e) young or (f) old animals. For intraperitoneal glucose tolerance tests (IPGTTs), blood glucose levels were measured after administration of glucose (2 g/kg i.p.). (g,h) Glucose tolerance was similar for both genotypes at 1 and 2 months. (i) At 3 months of age, Wfs1-ex5-KO232 rats showed a slight glucose intolerance compared with WT rats, which was exacerbated at (j) 6 months. (k) Area under the curve for IPGTT results at different ages. (l) Glucose-stimulated increases in blood insulin levels (relative to baseline) 30 minutes after glucose administration, Wfs1-ex5-KO232 animals showed a defect in insulin secretion after 3 months of age. Size distribution of islets of Langerhans in rats at (m) 3, (n) 7 and (o) 14 months of age. Islet mass in rats at (p) 3, (q) 7 and (r) 14 months of age. The data were compared using two-way ANOVAs followed by Tukey’s HSD tests; ^#p < 0.05, ^## < 0.01 between genotypes, *p < 0.05, **p < 0.01 within genotype (vs baseline and vs 3 months age). The data are presented as the mean ± SEM, n = 6–8.