[ Diabetes Solutions ]

Beta cells in type 1 diabetes: victims or activators of t cell response?

The Harvard Stem Cell Institute (HSCI), three of Harvard’s clinical affiliates, and a biopharmaceutical company have formed an unusual collaboration to establish the Boston Autologous Islet Replacement Program (BAIRT) to accelerate a cure for diabetes. Researchers at Joslin Diabetes Center now have identified a mechanism that triggers the problem, giving a chance to find targets for drugs to protect these crucial cells. The loss of beta-cells that characterizes type 1 diabetes reflects the net effects of destruction and regeneration. intermediate glucose concentrations. Because beta-cells can occur under different phenotypes that vary with age and with environmental conditions, we propose to use the term functional beta-cell mass as an assessment of a beta-cell population by the number of beta-cells and their phenotype or functional state. In type I, the immune system attacks and kills most of the beta cells in the pancreas, resulting in an inability to produce insulin. FoxO1 — a transcription factor, or protein that controls when genes are switched on or off — serves as a kind of gauge of the body’s nutritional status.

Another finding was increased expression of c-Myc, which probably contributes to an increase in the expression of lactate dehydrogenase and the development of beta-cell hypertrophy. The role for glucose in regulating Fas expression on beta cell membrane may support the clinical evidence that tight glucose control limits beta cell destruction in type 1 diabetic patients as well in patients undergoing islet cell transplantation. Designing a method to test molecules called tracers for the ability to bind specifically to beta cells was not an easy task. It is predicted that sustained expression of these differentiation factors will restore beta cell function and mass in type 1 diabetes. In the absence of prospective follow-up, it is generally thought that LADA patients have escape an acute form of the disease in infancy with a very slow autoimmune form of beta cell destruction. An alternative hypothesis, could that autoimmunity may a secondary phenomenon that occurs in genetically predisposed individuals after an increase in blood glucose levels. To our knowledge, this is the first demonstration that autophagy acts as a defense to cellular damage incurred during diabetes.


They took these findings to collaborators at Children’s Hospital Boston, who had previously developed a synthetic version of the protein. Of the two intermediary groups, the hazard ratio was 2.62 (P < .0001) for subjects who only had decreased insulin sensitivity (high IGI60/low ISI), vs 3.35 (P < .0001) for those with only decreased beta-cell function (low IGI60/high ISI). "At the present time, the quantities of insulin they secrete are not as great as with natural beta cells," he admits. Imagawa A, Hanafusa T, Tamura S, Moriwaki M, Itoh N, Yamamoto K, Iwahashi H, Yamagata K, Waguri M, Nanmo T, Uno S, Nakajima H, Namba M, Kawata S, Miyagawa JI, Matsuzawa Y. Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity. The inhibition of the activity of the DPP-IV enzyme enhances endogenous GLP-1 action in vivo, mediated not only by GLP-1 but also by other mediators. Rosmalen JG, Homo-Delarche F, Durant S, Kap M, Leenen PJ, Drexhage HA. Islet abnormalities associated with an early influx of dendritic cells and macrophages in NOD and NODscid mice. When the researchers transplanted these cells into diabetic, immune-deficient mice, they ameliorated high blood glucose for long periods of time. Horwitz MS, Ilic A, Fine C, Rodriguez E, Sarvetnick N. Targeted manipulation of these two pathways has shown that it is possible to induce beta cell differentiation from stem cells. J Clin Invest, 2002, 109, 79-87. Reprogramming Human Skin Cells to Produce Insulin. If this strand of RNA is not present, too few cells – if any – will divide. J Exp Med, 1999, 189, 331-339. Ploix C, Bergerot I, Durand A, Czerkinsky C, Holmgren J, Thivolet C. Oral administration of cholera toxin B-insulin conjugates protects NOD mice from autoimmune diabetes by inducing CD4+ regulatory T-cells. Diabetes, 1999, 48, 2150-2156. Malder K, Spinas GA, Lehman R, Sergeev P, Weber M, Fontana A, Kaiser N, Donath MY. Glucose induced beta cell apoptosis via upregulation of the Fas receptor in human islets. Diabetes, 2001, 50, 1683-1690. Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG. The site-specificity and the permanence of this process are the two key features. Nat Med, 2000, 6, 278-282.

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