Oophorectomy promotes islet amyloid formation in a transgenic mouse model of Type II diabetes

Aims/hypothesis. In Type II (non-insulin-dependent) diabetes mellitus, amyl oid depletes islet mass. We previously found that 81% of male human islet a myloid polypeptide (IAPP) transgenic mice but only 11% of female mice devel oped islet amyloid, suggesting that either testosterone promotes or ovarian products protect against amyloid deposition. Methods. We did a bilateral oophorectomy or sham procedure in female human IAPP transgenic mice (n = 11 and n = 8, respectively) and in female non-tra nsgenic mice (n = 7 and n = 9, respectively) at 6-8 weeks of age. Animals w ere followed for 1 year on a 9 % fat (w/w) diet. Before we killed them we m easured, fasting plasma human IAPP and did an intraperitoneal glucose toler ance test. Pancreatic content of IAPP and immunoreactive insulin (IRI) were estimated and pancreata were analysed for islet amyloid. Results. No amyloid was detected in either the sham-operated transgenic mic e or, as expected, in both groups of non-transgenic mice. In strong contras t, 7 of 11 (64%) oophorectomized mice developed islet amyloid (p < 0.05). A myloid deposition in the oophorectomized transgenic mice was not associated with any differences in incremental body weight, fasting human IAPP concen trations or glucose tolerance between the groups. Furthermore, pancreatic c ontent of mouse IAPP, human IAPP and immunoreactive insulin did not differ between groups. Conclusion/interpretation. Oophorectomy is associated with an enhancement o f islet amyloid formation in the absence of changes in glucose tolerance, c irculating IAPP or pancreatic content of IRI, mouse or human IAPP. Thus, th e early stages of islet amyloidogenesis seem to be independent of glucose t olerance, with ovarian products having a protective role.