Insulin transactivator MafA regulates intrathymic expression of insulin and affects susceptibility to type 1 diabetes.

Objective: Tissue-specific self-antigens are ectopically expressed within the thymus and play an important role in the induction of central tolerance. Insulin is expressed in both pancreatic islets and the thymus and is considered to be the primary antigen for type 1 diabetes. Here, we report the role of the insulin transactivator MafA in the expression of insulin in the thymus and susceptibility to type 1 diabetes.

Prevention and treatment of obesity, insulin resistance, and diabetes by bile acid-binding resin.

Bile acid-binding resins, such as cholestyramine and colestimide, have been clinically used as cholesterol-lowering agents. These agents bind bile acids in the intestine and reduce enterohepatic circulation of bile acids, leading to accelerated conversion of cholesterol to bile acids. A significant improvement in glycemic control was reported in patients with type 2 diabetes whose hyperlipidemia was treated with bile acid-binding resins.

Molecular scanning of the gene for programmed cell death-1 (PDCD-1) as a candidate for type 1 diabetes susceptibility.

Multiple genes are involved in the susceptibility to autoimmune type 1 diabetes. The immunoreceptor programmed cell death-1 (PDCD-1), an inhibitory costimulatory molecule regulating peripheral tolerance, was reported to play a role in the development of type 1 diabetes, making the human PDCD-1 gene, PDCD1, as a candidate for disease susceptibility. In this article, we sequenced all 5 exons and exon-intron junctions of PDCD1 in Japanese subjects, and found 10 sequence variants.

MHC-linked susceptibility to type 1 diabetes in the NOD mouse: further localization of Idd16 by subcongenic analysis.

Although major histocompatibility complex (MHC)-linked susceptibility is the strongest component, recent studies demonstrated that MHC-linked susceptibility to type 1 diabetes consists of multiple components both in humans and non-obese diabetic (NOD) mouse. In the NOD mouse, Idd16 has been mapped to the region adjacent to, but distinct from Idd1 in the MHC class II region. Establishment of subcongenic NOD.

Contribution of class III MHC to susceptibility to type 1 diabetes in the NOD mouse.

A recombinant major histocompatibility complex (MHC) with the same class III region as the NOD mouse, but different class II region from the NOD mouse was identified in the NON mouse, and NOD mice congenic for this recombinant MHC, NOD.NON-H2, was established. None of the congenic mice homozygous for the NON MHC developed type 1 diabetes, indicating that the NOD MHC is necessary for the development of type 1 diabetes.

Food hardness as environmental factor in development of type 2 diabetes.

The effect of hardness of the diet as an environmental factor on the development of diabetes was investigated in a mouse model of type 2 diabetes. NSY and control C3H/He mice were fed several types of dietary chow from 4 weeks of age. Autoclaved CRF-1, whose major components are almost the same as those of the MF diet except for increased pellet hardness, resulted in a significant reduction in body weight in both NSY (p<0.

Evidence for Cd101 but not Fcgr1 as candidate for type 1 diabetes locus, Idd10.

Among polygenes conferring susceptibility to type 1 diabetes in the NOD mouse, Idd10 on distal chromosome 3 has been shown to be important for disease susceptibility. In this study, we investigated the candidacy of Fcgr1 and Cd101 for Idd10, by congenic mapping and candidate gene sequencing. Among seven NOD-related strains studied, the IIS mouse was found to possess a recombinant Idd10 interval with the same sequence at Fcgr1 as the NOD mouse, but a different sequence at Cd101 from that in the NOD mouse with 10 amino acid substitutions.