Regulation of the production of islet amyloid polypeptide and its precursorforms. Role in the deposition of amyloid.

Project Details

Description

Patients with non-insulin dependent diabetes (NIDD) often rerpresent amyloid deposits in the endocrine pancreas, which could be both the cause and consequence of the prevailing beta cell dysfunction. Preliminary investigations have indicated that beta cells exhibit an increased production of insulin and IAPP following prolonged exposure to elevated glucose levels. This increase was more pronounced for IAPP than for insulin and particularly prominant for the calcium dependent rise in intracellular pro-IAPP. Preliminary electron microscopic observations indicate that the human beta cell preparations with an increased content in IAPP precursors contain foci of amyloid deposition which immunostain for precursorsequences in pro-IAPP. The following questions will be investigated; (1) Effect of chronically elevated glucose levels upon biosynthesis of IAPP and selective accumulation of IAPP precursors; (2) Effect of increased pro-IAPP synthesis upon formation of amyloid fibrils.; (3) Effect of regulators of calcium uptake and distribution upon (pro)IAPP synthesis and formation of fibrils.; (4) Identification in intact pancreas of beta cells which are involved in amyloid formation.
AcronymOZR320
StatusFinished
Effective start/end date1/01/9931/12/02

Keywords

  • beta cel pathology
  • diabetes
  • amyloidose

Flemish discipline codes in use since 2023

  • Basic sciences

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