Coordination Chemistry of Diabetes-Associated Islet Peptide Hormones

Chronic hyperglycemia resulting from impaired blood glucose homeostasis is a hallmark of diabetes mellitus (DM). In particular, type II DM is characterized by insulin resistance, in which cells fail to appropriately respond to normal or even elevated levels of insulin. Despite advances in pharmacological interventions, current approaches to treating DM provide only temporary symptomatic relief and cannot completely cure the disease, highlighting the need to reveal fundamental pathological mechanisms governing the endocrine system. Glucose homeostasis is regulated by the combined actions of pancreatic islet-derived peptide hormones (e.g., insulin, islet amyloid polypeptide, somatostatin, glucagon, pancreatic polypeptide, and ghrelin), and disruption of their interplay has been implicated in the molecular pathology of DM. Moreover, the bioavailability and distribution of transition metal ions can be altered in diabetic conditions, suggesting the potential interactions between metal ions and pancreatic hormones. In this review, we cover the coordination chemistry of these peptide-based hormones and summarize how their metal-binding properties influence conformational dynamics, misfolding, aggregation, and downstream cellular signaling pathways.