Islet amyloid polypeptide in proliferating pancreatic B cells during development, hyperplasia, and neoplasia in humans and mice.
The occurrence of islet amyloid polypeptide (IAPP) immunoreactivity was investigated in fetal pancreas, islet cell hyperplasia, and tumors in humans and mice. Transgenic mice heritably developing endocrine tumors of the pancreas (AVP/SV40, Rip 1 Tag2/Rip2PyST1 and Glu2-Tag strains) were used as murine models of islet cells proliferative disease. In the mouse, IAPP immunoreactivity was found in B cells at embryonic day 12 (E12), paralleling the onset of insulin immunoreactivity. In hyperplastic/dysplastic islets and in B-cell tumors of transgenic mice (n = 16), IAPP immunoreactivity was localized consistently to insulin-immunoreactive cells. Ultrastructural single- and double-immunogold labeling of transgenic mice B-cell tumors (n = 3) showed insulin and IAPP to be colocalized in beta granules. In human fetuses, IAPP immunoreactivity was found in insulin-immunoreactive B cells, but at a later gestational age than the onset of insulin immunoreactivity. In pancreatic specimens of infantile/neonatal persistent hyperinsulinemic hypoglycemia (11 cases) and in pancreatic endocrine tumors (21 cases, 10 of which were functioning insulinomas), IAPP immunoreactivity was found consistently in insulin-immunoreactive B cells. Congo-red-positive amyloid deposits present in tumors also were IAPP immunoreactive. Ultrastructural single and double immunogold labeling of infantile/neonatal persistent hyperinsulinemic hypoglycemia cases (n = 3) and functioning insulinomas (n = 2) showed IAPP and insulin to be colocalized in beta granules. In addition, IAPP immunoreactivity was observed in amyloidlike fibrils. These findings indicate that IAPP is a constitutive component of B cells. Possible relationships between IAPP and insulin expression and interspecies differences are suggested and discussed.
Rindi
G
G
Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Terenghi
G
G
Westermark
G
G
Westermark
P
P
Moscoso
G
G
Polak
J M
JM
D007516:Adenoma, Islet Cell / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D002455:Cell Division; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
D000682:Amyloid; D058228:Islet Amyloid Polypeptide