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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

Subject Area Endocrinology, Diabetology, Metabolism
Gastroenterology
Term from 2017 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 391323037
 
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.
DFG Programme Research Grants
 
 

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