Although many important insights have and will continue to come from studies of rodent islets, the significant differences between islets from rodents and humans and the failure of many rodent findings to be conserved in human islet biology underscores the need for studies using human tissue.
As expected the comparison between islets from ob/ob and WT mice identified many of the genes previously identified that play a role in β-cell expansion during states of insulin resistance such as obesity and pregnancy [ 15].
Data analysis To identify differentially expressed genes between islets from non-pregnant and P15.5 mice with the MOE430_2.0 and MoGene_1.0_ST arrays (p < 0.001), the probe sets of both platforms, unambiguously annotating the same gene, were analysed, resulting in an expression dataset of 17,337 genes.
Using real-time PCR no differences in Kv1.1 expression levels (relative to 18S) were observed between islets from three non-diabetic and three diabetic individuals.
Islet size was similar between islets from wild type and KO mice (12426±510 µm2 for ERαWT and 12123±415 µm2 for ERαKO; 15720±612 µm2 for ERβWT and 15977±764 µm2 for ERβKO; at least 100 islets from at least 3 different mice).
No significant differences were noticed between islets from wild-type mice and from LXRα-/-mice, while absence of LXRβ was associated with a markedly reduced expression of SCD1 and 2, and of SREBP1c (Figure 5b), and higher expression of DGAT1, SOAT1, and ELOvl5 (Table S2).
The other genes in the GABA signalling cascade (Fig. 1b) were all similarly expressed and did not differ significantly between islets from individuals with type 2 diabetes and those from normoglycaemic donors.
First we analyzed the list of significantly up-regulated genes in islets from the comparison between ob/ob and WT mice that were not significantly changed in the comparison between POKO and WT mice.
We also considered the possibility that these differences between human and mouse islets might have resulted from the shipping of human islets from the isolation centre.
Islets from the pancreases were transplanted into mice with diabetes.
