Localisation of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of type-2 diabetic subjects.
Islet amyloid peptide (or diabetes-associated peptide), the major component of pancreatic islet amyloid found in type-2 diabetes, has been identified by electron-microscopic immunocytochemistry in pancreatic B-cells from five non-diabetic human subjects, and in islets from five type-2 diabetic patients. The greatest density of immunoreactivity for islet amyloid peptide was found in electron-dense regions of some lysosomal or lipofuscin bodies. The peptide was also localised by quantification of immunogold in the secretory granules of B-cells, and was present in cytoplasmic lamellar bodies. Acid phosphatase activity was also demonstrated in these organelles. Immunoreactivity for insulin was found in some lysosomes. These results suggest that islet amyloid peptide is a constituent of normal pancreatic B-cells, and accumulates in lipofuscin bodies where it is presumably partially degraded. In islets from type-2 diabetic subjects, amyloid fibrils and lipofuscin bodies in B-cells showed immunoreactivity for the amyloid peptide. Abnormal processing of the peptide within B-cells could lead to the formation of islet amyloid in type-2 diabetes.
Clark
A
A
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, England.
Edwards
C A
CA
Ostle
L R
LR
Sutton
R
R
Rothbard
J B
JB
Morris
J F
JF
Turner
R C
RC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008062:Lipofuscin / Q000378:metabolism*; D008297:Male; D010860:Pigments, Biological / Q000378:metabolism*
D000682:Amyloid; D008062:Lipofuscin; D010860:Pigments, Biological