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. 2013 Jun 24;8(6):e61870. doi: 10.1371/journal.pone.0061870

Figure 3. Mutation of Mll2 leads to impaired glucose tolerance and insulin resistance and impaired insulin secretion in isolated Islets.

Figure 3

A: Plasma glucose measured in an intraperitoneal glucose tolerance test in male mice at 12 weeks of age, animals heterozygous for Mll2M2628K/+ (red circles N = 20), Mll2F2648I/+ (blue diamonds N = 7) and the Mll2+/− Knockout (green squares N = 16) show impaired glucose tolerance compared to wild-type littermates (black triangles N = 22) B: Plasma glucose measured during a 30 minute IPGTT in male mice at 16 weeks of age, animals heterozygous for the Mll2M2628K/+ (red circles N = 14), Mll2F2648I/+ (blue diamonds N = 7) and the Mll2+/− Knockout (green squares N = 12) show impaired glucose tolerance compared to wild-type littermates (black triangles N = 25) C: Plasma insulin measured during a 30 minute IPGTT in male mice at 16 weeks of age, animals heterozygous for Mll2M2628K/+ (red circles N = 14), Mll2F2648I/+ (blue diamonds N = 7) and the Mll2+/− Knockout (green squares N = 12) exhibit fasting hyperglycaemia and fail to secret insulin in response to a glucose challenge in comparison to wild-type littermates (black triangle N = 25). D: Insulin tolerance tests carried out on male mice at 12 weeks of age. Data was normalized for differences in fasting glucose levels, response to insulin load was reduced in animals heterozygous for Mll2M2628K/+ (red circles N = 9), Mll2F2648I (blue diamonds N = 7) and the Mll2+/− Knockout (green squares N = 10) compared to wild-type littermates (black triangles N = 9). E: Insulin secretion from islets isolated from Mll2M2628K/+ (red bars), Mll2F2648I/+ (blue bars) Mll2+/− Knockout (green bars) and wild-type littermates (black bars) in response to glucose (2, 10, 20 mM or tolbutamide (tol, 200 mM+2 mM Glucose)). Both the Mll2M2628K/+ and Mll2F2648I/+ Islets hypersecrete insulin at 2 mM glucose, insulin was elevated in the Mll2+/− islets but this failed to reach significance. Islets were isolated from 5 mice of each genotype. F: Insulin secretion data expressed as fold change. The data represent the mean of 5 animals (with 4 technical replicates per animal of 5 islets). All data are presented as Mean ± SEM, * p<0.05, **p<0.01, ***p<0.001, pairwise comparison student's t-test (compared to wt littermates).