Increased amounts of a high molecular weight insulin-like growth factor II (IGF-II) peptide and IGF-II messenger ribonucleic acid in pancreatic islets of diabetic Goto-Kakizaki rats.
Insulin-like growth factor II (IGF-II), a member of the insulin family, regulates cell growth and differentiation. The IGF-II gene is localized close to the insulin gene in man and rat. IGF-II peptide binds weakly to the insulin receptor and exerts insulin-like effects on the blood glucose level. We studied IGF-II in endocrine pancreas in an animal model of noninsulin-dependent diabetes mellitus, the Goto-Kakizaki (GK) rat. At the age of 2 months, these rats have structural islet changes, with fibrosis and irregular configuration, so-called starfish-shaped islets. Immunohistochemical investigation revealed IGF-II immunoreactivity in the beta-cells in both GK and control rats. Pancreatic extraction, followed by size separation using gel chromatography, disclosed a high mol wt form of IGF-II in all animals, and RIA measurements revealed a considerably larger amount of the IGF-II peptide in the 2-and 6-month-old GK rats than in the 1-month GK and control rats. In situ hybridization of 3-month-old GK rats showed increased IGF-II messenger RNA expression in the starfish-shaped islets of GK rats than in the islets with normal structure in both diabetic and control animals. The reason for the increased amount of IGF-II is unclear. As the animals are diabetic before the islet changes occur, it might be a compensatory effect in response to hyperglycemia, but could also be a cause of the islet fibrosis.
Höög
A
A
Department of Tumor Pathology, Karolinska Institute and Hospital, Stockholm, Sweden. andersh@path.ks.se
Sandberg-Nordqvist
A C
AC
Abdel-Halim
S M
SM
Carlsson-Skwirut
C
C
Guenifi
A
A
Tally
M
M
Ostenson
C G
CG
Falkmer
S
S
Sara
V R
VR
Efendić
S
S
Schalling
M
M
Grimelius
L
L
D000818:Animals; D001835:Body Weight; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D017403:In Situ Hybridization; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism
D018970:Insulin-Like Growth Factor Binding Protein 1; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin