Reduced expression of receptors for the incretin hormones GIP and GLP-1 as a potential cause of an impaired GIP- or GLP-1-mediated augmentation of insulin secretion in type 2-diabetes

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In the proposed research project the following question will be addressed: Is the Expression of receptors for the incretin hormones GIP (Glucose-dependent Insulinotropic Peptide) and GLP-1 (Glucagon-Like Peptide-1) on beta cells in the endocrine pancreas reduced in subjects with type 2 diabetes mellitus compared to metabolically healthy control subjects?This question is derived from findings documenting a much reduced insulinotropic effectiveness of both incretin hormones, namely GIP, in subjects with type 2 diabetes. Animal experiments have already provided hints towards a reduced expression of incretin hormone receptors in diabetic rodent models. Examinations of GIP- and/or GLP-1 receptors in human subjects with and without diabetes mellitus are completely lacking. The task of findings anwers to the central question of the project requires a bank of pancreatic tissue from patients, whose clinical data concerning glucose metabolism have been meticulously documented and the employment/optimization of challenging techniques like microdissection for the examination of the expression of GIP and GLP-1 receptors at the mRNA and protein level as well as with a radio-ligand assay, since the endocrine pancreas makes up only 1-2 % of the total pancreatic tissue mass. Surgical pancreatic tissue specimens are available from 26 type 2-diabetic subjects and 95 patients without diabetes mellitus. The techniques to be employed in the project have been developed to the degree, that they can be used successfully.