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Key discoveries significant to the improved treatment of diabetes

2001   First conclusive demonstration that a low fat diet and moderate exercise reduce likelihood of becoming diabetic by 50%; treatment with metformin reduces likelihood by one third.
2001   Discovery and isolation of pluripotential stem cells within the pancreatic islets of Langerhans which can be grown in culture and differentiated into insulin-producing cells.
2000   First use of a functional strategy to identify a protein that regulates GLUT4 glucose transporter activity.
2000   Development of a transgenic mouse model of age-dependent diabetes mellitus as a result of pancreatic b-cell IDX-1-deficiency.
1999   Discovered the Bridge-1 gene and demonstrated that it activates insulin gene expression.
1999   Performed first comprehensive evaluation of genetic variations putatively associated to type 2 diabetes, and demonstrated an association to a genetic variant of the target of the anti-diabetic thiazolidinedione (TZD) drugs, PPAR-gamma.
1999   First evidence that the secretion of hormones (e.g. ACRP30) from fat is specifically regulated by insulin.
1998   Characterization of the specific components of the insulin resistance syndrome, and its relationship with glycemia
1997   Discovery that GLP-1 stimulates the expression of the IDX-1 transcription factor and promotes the formation of new beta-cells in the pancreas from stem cells.
1993   Discovery of a gene, IDX-1, that proves to be a master regulator of pancreas development and a key controller of insulin gene expression.
1993   First definitive proof of the benefits of intensive therapy to prevent complications in Type 1 diabetes, such as heart disease.
1992   First human proof that the administration of GLP-1 to type 2 diabetic subjects stimulates endogenous insulin secretion and effectively lowers blood glucose levels.
1986   First demonstration of the relationship of hyperglycemia and risk for retinopathy (eye damage) in Type 2 diabetes.
1985   First use of implantable pumps to treat diabetes.
1985   Discovered a novel hormone, glucagon-like peptide (GLP-1) and demonstrated that it stimulates insulin secretion and enhances the transcriptional expression of the insulin gene.
1984   First demonstration of the clinical utility of HbA1c (glucose modified hemoglobin) assay, which estimates average blood sugar levels over the past few weeks.
1981   First successful transplantation of islets without immunosuppression.
1980   First successful isolation of pancreatic Islets of Langerhans from mice.   Top

Key steps leading to the first successful treatment to reverse established autoimmune diabetes:

2001   First treatment to reverse established autoimmune (Type 1) diabetes, using TNF-alpha and MHC class I and self peptide. This demonstated for the first time that disease removal was sufficient to allow spontaneous islet regeneration in the mouse.
2000   First demonstrated that TNF-alpha will induce cell suicide in autoimmune prone cells.
1999   First demonstration that the LMP2 protein defect plays a role in altering T cell death and allowing immune escape.
1997   First recognition that a mutation in the autoimmune prone NOD mouse reduces expression of both Tap1 and Lmp2, causing poor immune system education for self tolerance.
1991   First identification of LMP/TAP gene malfunction in autoimmune prone animals. This malfunction in murine autoimmunity was leading to interrupted MHC class I presentation for self tolerance and interrupted NfkB signalling.
1991   First identification of MHC class I as a structure of T cell tolerance to self and the disruption of this pathway in autoimmunity.
1991   First introduction of a novel technique to prevent rejection of transplanted cells. The method of donor protein modification was expanded within industry into world-wide clinical trials.
1989   First identification of an over abundance of naive T cells in the peripheral blood of diabetic patients. This is now recognized as a defect in T regulatory cells.
1980   First demonstration of MHC class I antigens on tissue cells such as the insulin secreting cells of the pancreas.   Top

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