Islet amyloid polypeptide (IAPP) has been implicated by in vitro studies as an inhibitor of insulin-stimulated glucose utilization by skeletal muscle cells and also as an inhibitor of insulin-stimulated insulin secretion by beta cells. Increased expression and production of IAPP by beta cells, as has been suggested to occur in cats with impaired glucose tolerance, could thus contribute substantially to the development of the insulin resistance and impaired insulin release which are the hallmarks of Type 2 diabetes mellitus. The effects of IAPP with respect to glucose metabolism in living animals, however, have not been previously reported. In the present in vivo study we show that synthetic amidated IAPP induced impaired glucose tolerance in each of the 3 cats studied, with dramatic impairment (increases in glucose to T 1 2 values of 124% and 234%) in 2 of the 3 cats. Impaired insulin responses were also evident in the 2 cats with the most dramatic states of glucose intolerance. These results provide the most direct evidence to-date that IAPP may have an important role in the development of Type 2 diabetes mellitus.
|Original language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Mar 16 1990|
Bibliographical noteFunding Information:
Acknowledgments: The authors are grateful to Ms. Kathleen Burg for valuable technical assistance. This study was supported by Grant ROl DK36734 of the National Institute of Diabetes and Digestive and Kidney Disease, the Swedish Medical Research Council (Project No. 5941) the Research fund of King Gustaf V, the Nordic Insulin Fund, and Louis-Hansen's Memorial Fund.