1994
DOI: 10.2337/diab.43.2.329
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Islet Amyloid Polypeptide in Human Insulinomas: Evidence for Intracellular Amyloidogenesis

Abstract: Amyloid deposits that characteristically form in the pancreatic islets of patients with non-insulin-dependent diabetes mellitus (NIDDM) and in insulinomas are both derived from islet amyloid polypeptide (IAPP). Evidence from previous studies has suggested that deposition of IAPP-derived amyloid is related to inherent amyloidogenic sequences present within normal human IAPP, together with an increased production and local concentration of IAPP. However, whether the aggregation of IAPP to form amyloid fibrils is… Show more

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Cited by 81 publications
(63 citation statements)
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“…Furthermore, only a minority (ϳ10%) of the cases with IFG had islet amyloid present, while they already had a deficit in presumptive ␤-cell mass of ϳ40%. These data are consistent with the previously stated hypothesis that small IAPP oligomers (not detectable by light microscopy) are the cause of ␤-cell loss, whereas the large extracellular amyloid deposits visible by light microscopy are inert (16,25). Alternatively, it is possible that the formation of islet amyloid is secondary to hyperglycemia and not of primary importance in the pathophysiology of type 2 diabetes.…”
Section: Discussionsupporting
confidence: 92%
See 1 more Smart Citation
“…Furthermore, only a minority (ϳ10%) of the cases with IFG had islet amyloid present, while they already had a deficit in presumptive ␤-cell mass of ϳ40%. These data are consistent with the previously stated hypothesis that small IAPP oligomers (not detectable by light microscopy) are the cause of ␤-cell loss, whereas the large extracellular amyloid deposits visible by light microscopy are inert (16,25). Alternatively, it is possible that the formation of islet amyloid is secondary to hyperglycemia and not of primary importance in the pathophysiology of type 2 diabetes.…”
Section: Discussionsupporting
confidence: 92%
“…The autopsy process does not include full dissection and removal of the retroperitoneal pancreas to determine pancreas weight (as is routinely possible in rodent studies with a more accessible pancreas). Sections were cut from these paraffin blocks and stained by Congo Red for hematoxylin/eosin and by immunohistochemistry for insulin, as previously described (25). In addition, sections were analyzed for replication by immunohistochemistry for Ki67 (anti-Human Ki-67 monoclonal antibody MIB-1, 1/25; Dako, Carpinteria, CA) (26) and for apoptosis using the TdT-FragEL Kit (cat.…”
Section: Methodsmentioning
confidence: 99%
“…Congo red is a reliable, practical, and sensitive technique for detecting amyloid deposits containing islet amyloid polypeptide (IAPP) or amylin (22,23). IAPP is the building block of islet amyloid deposits (5,10,24).…”
Section: Methodsmentioning
confidence: 99%
“…Congo red staining or birefringence are inadequate for the detection of small deposits of amyloid fibrils. The autofluorescent properties of Congo red, however, served to detect small needlelike structures by using UV-light microscopy, suggesting an intracellular origin of amyloid deposits (4).…”
Section: Iapp Expression In Relation To Amyloidogenesismentioning
confidence: 99%
“…In over 50% of insulinomas investigated, amyloid deposits have been demonstrated (2)(3)(4). The major protein component of these deposits was identified as islet amyloid polypeptide (IAPP) (5,6).…”
Section: Introductionmentioning
confidence: 99%