BioProject

Immediate and early effects of transient hyperglycaemia were examined using fully- reversible transgenic diabetic mice. More...

Immediate and early effects of transient hyperglycaemia were examined using fully- reversible transgenic diabetic mice. Transient hyperglycaemia altered expression of 769 arterial genes, of which 200 did not reverse following recovery from hyperglycaemia. Many such genes are known to promote atherogenesis, including several implicated in arterial calcification and inflammation. This supports the view that hyperglycaemia causes not only very early deleterious changes in arterial gene expression but that to a large extent these persist for some time after restoration of normal blood glucose levels in vivo. Together, results support the contention that avoiding excess CVD risk in diabetes requires very early correction of hyperglycaemia. Overall design: As shown previously (Pelengaris et al., 2002 Cell), c-MycERTAM protein is activated in pancreatic beta cells of adult transgenic mice, by daily intraperitoneal (IP) administration of tamoxifen (TAM; Sigma-Aldrich, Dorset, UK) (1 mg/0.2 ml in peanut oil). Inactivation of c-MycERTAM protein was achieved through withdrawal of TAM. Adult female mice, 3-6 months of age, inbred into CBA-C57Bl/6 background and maintained under barrier conditions, were treated with TAM for up to 7 days (Myc ‘ON’) and then monitored during recovery for more than 4 months (140 days) (Myc ‘OFF’). Experimental timepoints were: Days 2, 4 and 7: c-Myc ‘ON’; days 0, 11, 26: c-Myc ‘OFF’. Biological replicates: each timepoint included 3 biological replicates (n=3 mice). Less...