A pancreatic β-cell-specific homolog of glucose-6-phosphatase emerges as a major target of cell-mediated autoimmunity in diabetes

摘要: Diabetes has been termed the epidemic of 21st century and over past 50 years in Western societies doubling incidence every 15 years. It exacts a huge socioeconomic toll because its devastating microvascular macrovascular complications need patients to maintain lifetime daily therapeutic regimen. The childhood-onset form diabetes, which accounts for 10% all cases humans [autoimmune or type 1 diabetes (IDDM)], is product T lymphocyte-dependent autoimmune process that specifically destroys insulin-secreting β cells pancreas without affecting contiguous endocrine surrounding exocrine tissue (1). Such cell specificity might logically be an reactivity directed at β-cell-specific molecular targets mediated by direct cellular contact between target effector cytotoxic lymphocytes. article Lieberman et al. (2) recent issue PNAS supports such notion identifies diabetogenic CD8 diabetes-susceptible nonobese diabetic (NOD) mice as protein islet glucose-6-phosphatase (G6Pase) catalytic subunit-related (IGRP). Moreover, it shows on basis antigen receptor (TCR) Vα-chain usage TCR studied these experiments represents dominant NOD mouse, are major component population infiltrating up onset (3). Type polygenic disorder both mouse involving ≥20 loci (4) but with contribution susceptibility from MHC class II region (up 50% humans). only other alleles un-equivocally identified lie within variable number tandem repeat insulin gene (IDDM2) CTLA-4 (IDDM12) …