ISLET AMYLOID POLYPEPTIDE AMYLIN CONTENTS IN PANCREAS CHANGE WITH INCREASING AGE IN GENETICALLY-OBESE AND DIABETIC MICE/

To search for a possible relationship between islet amyloid polypeptid e (IAPP)/amylin and the pathophysiology of non-insulin-dependent (type 2) diabetes mellitus (NIDDM), we examined the changes in IAPP content s in the pancreata of genetically obese and diabetic mice (C57BL/6J ob /ob and C57BL/KsJ db/db mice). In the male ob/ob mice, IAPP and insuli n contents began to increase at 16 weeks and continued to increase. In the male db/db mice, IAPP content began to increase at 8 weeks of age and insulin content at 4 weeks. Both contents continued to increase u ntil 16 weeks, but drastically decreased at 24 weeks. Immunohistochemi cal studies using anti-IAPP(8-17) antibody showed the increase of isle t cell mass and the heterogeneous immunoreactivity for IAPP in islet c ells in the ob/ob mice at 24 weeks of age. In the db/db mice at the sa me age, the immunoreactivity was heterogeneous and weak in many islet cells. These results suggest that genetic factors that are important i n the manifestation of NIDDM influence the capacity of beta-cells to s ynthesize and secrete IAPP, and that IAPP synthesis and secretion chan ge in the course of the disease.