Explaining Type 2 Diabetes with Transcriptomic Signatures of Pancreatic β-Cell Dysfunction and Death Induced by Human Islet Amyloid Polypeptide.

Amyloid deposits formed by misfolding and aggregation of human islet amyloid polypeptide (hIAPP) are one of the key pathophysiological features of type 2 diabetes mellitus (T2DM) and have been associated with the loss of function and viability of the pancreatic β-cells. The molecular processes by which hIAPP induces cytotoxicity in these cells are not well understood. To the best of our knowledge, this is the first report describing findings from the combined analysis of Affymetrix microarray and high-throughput sequencing (HTS) Gene Expression Omnibus (GEO) datasets of h-transgenic (Tg) mice islets.

Metabolic perturbations associated with hIAPP-induced insulin resistance in skeletal muscles: Implications to the development of type 2 diabetes.

The human islet amyloid polypeptide (hIAPP) tends to misfold and self-assemble to form amyloid fibrils, which has been associated with the loss of function and viability of pancreatic β-cells in type 2 diabetes mellitus (T2DM). The role of hIAPP in the development of insulin resistance (a hallmark of T2DM) in skeletal muscles - the major sites for glucose utilization - needs further investigation. Even though, insulin-resistant conditions have been known to stimulate hIAPP aggregation, the events that lead to the development of insulin resistance due to hIAPP aggregation in skeletal muscles remain unidentified.