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Diabetes
Type-1 diabetes mellitus is an organ-specific autoimmune disease due to a lack of endogenous insulin. Insulin is the hormone which maintains blood glucose homeostasis. There is a high incidence rate worldwide and according to WHO, over 5 million people live with type I diabetes. It is a debilitating disease with medical complications and a decreased life expectancy. Destruction of insulin producing cells in the pancreas is mediated by an auto reactive immune response. A strong correlation between type I diabetes and genetic risks factors, especially expression of certain HLA alleles, has been identified. A major result of diabetes is lymphocytic infiltration into the pancreatic islets of Langerhans causing the destruction of insulin producing β-cells.
Insulin has been identified as one of the autoantigens involved in this disease and antibodies to insulin are seen commonly in young diabetic patients. Islet cell antigens play an important role as predictive markers for diabetes by distinguishing an autoimmune aetiology. Three distinct targets have been identified. Glutamic acid decarboxylase (GAD65) along with proteins from the tyrosine phosphatase superfamily IA-2 and phogrin (IA-2β). Phogrin is not commonly found to be clinically relevant. GAD65 is considered to be one of the most relevant AAB predictors with IA-2 also playing a key role. IA-2 and IA-2β have quite a high sequence homology but there relative functions are still not fully understood. Zinc transporter 8 is also considered to be relevant as a type I diabetes mellitus autoantigen more so in adult onset autoimmune diabetes.
References:
Pietrapaolo et al, Pediatr Diabetes 2005 6(4):184-92
Lan et al, DNA Cell Biol 1994 13:505-14
Helmke et al, Diabetologia 1986 29:30-33
Pociot F and McDermott MF, Genes Immun 2002 3:235-249
Lernmark A, Intern. Med. 1996 240:259-277
Palmer et al, Science 1983 222:1337-9
Bottazzo GF, Florin-Christensen A and Doniach D, Lancet 1974 2:1279-83
Insulin has been identified as one of the autoantigens involved in this disease and antibodies to insulin are seen commonly in young diabetic patients. Islet cell antigens play an important role as predictive markers for diabetes by distinguishing an autoimmune aetiology. Three distinct targets have been identified. Glutamic acid decarboxylase (GAD65) along with proteins from the tyrosine phosphatase superfamily IA-2 and phogrin (IA-2β). Phogrin is not commonly found to be clinically relevant. GAD65 is considered to be one of the most relevant AAB predictors with IA-2 also playing a key role. IA-2 and IA-2β have quite a high sequence homology but there relative functions are still not fully understood. Zinc transporter 8 is also considered to be relevant as a type I diabetes mellitus autoantigen more so in adult onset autoimmune diabetes.
References:
Pietrapaolo et al, Pediatr Diabetes 2005 6(4):184-92
Lan et al, DNA Cell Biol 1994 13:505-14
Helmke et al, Diabetologia 1986 29:30-33
Pociot F and McDermott MF, Genes Immun 2002 3:235-249
Lernmark A, Intern. Med. 1996 240:259-277
Palmer et al, Science 1983 222:1337-9
Bottazzo GF, Florin-Christensen A and Doniach D, Lancet 1974 2:1279-83
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