| First Author | Taylor AJ | Year | 2023 |
| Journal | Mol Metab | Volume | 68 |
| Pages | 101667 | PubMed ID | 36621763 |
| Mgi Jnum | J:333476 | Mgi Id | MGI:7438720 |
| Doi | 10.1016/j.molmet.2023.101667 | Citation | Taylor AJ, et al. (2023) Islet amyloid polypeptide does not suppress pancreatic cancer. Mol Metab 68:101667 |
| abstractText | OBJECTIVES: Pancreatic cancer risk is elevated approximately two-fold in type 1 and type 2 diabetes. Islet amyloid polypeptide (IAPP) is an abundant beta-cell peptide hormone that declines with diabetes progression. IAPP has been reported to act as a tumour-suppressor in p53-deficient cancers capable of regressing tumour volumes. Given the decline of IAPP during diabetes development, we investigated the actions of IAPP in pancreatic ductal adenocarcinoma (PDAC; the most common form of pancreatic cancer) to determine if IAPP loss in diabetes may increase the risk of pancreatic cancer. METHODS: PANC-1, MIA PaCa-2, and H1299 cells were treated with rodent IAPP, and the IAPP analogs pramlintide and davalintide, and assayed for changes in proliferation, death, and glycolysis. An IAPP-deficient mouse model of PDAC (Iapp(-/-); Kras(+/LSL-G12D); Trp53(flox/flox); Ptf1a(+/CreER)) was generated for survival analysis. RESULTS: IAPP did not impact glycolysis in MIA PaCa-2 cells, and did not impact cell death, proliferation, or glycolysis in PANC-1 cells or in H1299 cells, which were previously reported as IAPP-sensitive. Iapp deletion in Kras(+/LSL-G12D); Trp53(flox/flox); Ptf1a(+/CreER) mice had no effect on survival time to lethal tumour burden. CONCLUSIONS: In contrast to previous reports, we find that IAPP does not function as a tumour suppressor. This suggests that loss of IAPP signalling likely does not increase the risk of pancreatic cancer in individuals with diabetes. |
