A deletion in the 3’ region of the mouse Ank1 gene affects glucose homeostasis

The contractile activity of skeletal muscle tissue supports voluntary body movements, sustains body posture, and participates in regulating body temperature and metabolism. Skeletal muscle contraction depends on an extensive amount of ATP hydrolysis, required, at the level of single myofibers, both by myosin to initiate myofilaments sliding and by SERCA pump to restore low cytosolic Ca2+ levels to allow muscle relaxation. Accordingly, skeletal muscles depend on a continuous supply of glucose, the elective oxidative substrate to fulfill such abundant ATP demand. Being the largest insulin-sensitive tissue, skeletal muscle tissue also represents the main site of insulin-dependent glucose absorption after meals. Therefore, impaired glucose uptake by this tissue may cause altered glucose homeostasis and metabolic disorders that can result in pathological conditions, where Type 2 Diabetes (T2D) is the most frequent disease. T2D is a multifactorial disease whose development is determined by both non-genetic and genetic factors. Over the past years, GWAS identified hundreds of single nucleotide polymorphisms (SNPs) associated to T2D-susceptibility in a high number of genes. In particular, recent data identified a T2D-associated SNP (rs-508419) in the 3' region of the ANK1 gene, in a genomic area corresponding to a muscle-specific stretch/super-enhancer chromatin domain. To verify whether this genomic region regulates glucose homeostasis, we analyzed glucose parameters in a mouse model carrying a deletion in this region. Our results confirm that a deletion in this regulatory region affects glucose tolerance fasting glycemia, and additional glucose related parameters.