More than a decade after the discovery of a novel type 1 diabetes risk locus on chromosome 16p13, there remains complexity and controversy over the specific gene(s) that regulate diabetes pathogenesis.A new study by Nieves-Bonilla et al. shows that one of these genes, DEXI, is unlikely to contribute to type 1 diabetes pathogenesis and positions the endolysosomal E3 ubiquitin ligase CLEC16A as the primary culprit by which this gene locus influences diabetes risk.
Some of the deregulated proteins such as thioredoxin 2, glutathione S transferase, T complex protein 1 subunit β (tcbp1), heat shock protein 90 and E3 ubiquitin ligase were previously reported to be associated with either diabetes or insulin resistance.
PARK2 mutations are associated with juvenile parkinsonism, Alzheimer disease, cancer, leprosy, and diabetes mellitus, yet ironically, there has been no comprehensive study of PARK2 in control subjects; and to resolve controversial association of PARK2 heterozygous mutations with Parkinson disease (PD) in a well-powered study.
MAFbx/Atrogin-1 is a muscle specific E3 ubiquitin ligase upregulated during disuse, immobilization and fasting or systemic diseases such as diabetes, cancer, AIDS and renal failure.