The third extracellular loop and the intracellular carboxy-terminus of chimera A with the corresponding glucagon receptor segments re-established the ability to distinguish GLP-1(21-37) from the chimeric peptide GLP-1(7-20). Are homologous family B seven-transmembrane (7TM) G protein-coupled receptors helices and connecting loops, determines specificity for the carboxyl terminus of glucagon and GLP-1, respectively. Corroborant results were obtained with the opposite chimeric peptide glucagon also known as 7-37 for the codons of the preproglucagon molecule.
Other candidate genes (e.g. insulin, insulin receptor, glucose transporters) have been excluded as major diabetogenes. Neither subtype of NIDDM is present, the mutation plays little, if any, role in susceptibility to diabetes. which is reflective of other populations genetic susceptibility to NIDDM and other complex traits in different ethnic groups (NIDDM) affects about 5% of the world population. The disease presents a polygenic mode of inheritance, but mechanisms and genes involved in late-onset NIDDM are largely unknown.
Such intra-systemic mimicry of self-proteins also raises complex questions about how "self" and "nonself" are regulated during TCR production. By screening of libraries originally targeted to mimic the binding of the glucagon-like peptide (GLP-1) hormone to its receptor. TCR mimicking insulin and its receptor may be targets of anti-insulin autoantibodies. Such "complementarity", if it exists, could either serve to down-regulate the clones bearing such TCR or T-cell receptors , alternatively, trigger an intra-immune system civil war between them,‡. Copyright (c) 2008 John Wiley & Sons, Ltd.