Extended life span is associated with insulin resistance in a transgenic mouse model of insulinoma secreting human islet amyloid polypeptide

摘要

Pancreatic amyloid is found in patients with insulinomas and type 2 diabetes. To study mechanisms of islet amyloidogenesis, we produced transgenic mice expressing the unique component of human islet amyloid, human islet amyloid polypeptide (hIAPP). These mice develop islet amyloid after 12 mo of high-fat feeding. To determine whether we could accelerate the rate of islet amyloid formation, we crossbred our hIAPP transgenic animals with RIP-Tag mice that develop islet tumors and die at 12 wk of age from hypoglycemia. At 12 wk of age, this new line of MAPPX RIP-Tag mice was heavier (29.7+-1.0 vs. 25.0+-1.3 g, P < 0.05) and had increased plasma glucose levels (4.6+-0.4 vs. 2.9+-0.6 mmol/1, P < 0.05) compared with littermate RIP-Tag mice.