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 locali zed close to the insulin gene in man and rat. IGF-II peptide binds wea kly to the insulin receptor and exerts insulin-like effects on the blo od glucose level. We studied IGF-II in endocrine pancreas in an animal model of noninsulin-dependent diabetes mellitus, the Goto-Kakizaki (G K) rat. At the age of 2 months, these rats have structural islet chang es, with fibrosis and irregular configuration, so-called starfish-shap ed islets. Immunohistochemical investigation revealed IGF-II immunorea ctivity in the beta-cells in both GK and control rats. Pancreatic extr action, followed by size separation using gel chromatography, disclose d a high mol wt form of IGF-II in all animals, and RIA measurements re vealed a considerably larger amount of the IGF-II peptide in the 2- an d 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 messenge r 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 compensator y effect in response to hyperglycemia, but could also be a cause of th e islet fibrosis.