Amylin role in glucose homeostasis and β-cell function: a robust justification

Amylin is a peptide hormone co-secreted with insulin from pancreatic β-cells that plays a crucial role in glucose homeostasis. Amylin by inhibiting glucagon secretion, slowing gastric emptying, and reducing food intake improves blood glucose and insulin sensitivity. However, emerging evidence suggests that amylin may also contribute to β-cell dysfunction and the development of insulin resistance (IR) in type 2 diabetes (T2D). This review explores the dual roles of amylin in T2D pathogenesis and management, highlighting its therapeutic and pathogenic implications. High amylin levels are associated with amyloid fibril formation, β-cell cytotoxicity, and progression of T2D complications. Conversely, amylin analogues have been shown to improve glycemic control, promote weight loss, and enhance energy balance via dual activation of amylin and calcitonin receptors in the hypothalamus. Experimental and clinical data demonstrate that both detrimental and protective effects of amylin are depending on concentration, duration, and receptor interaction. Amylin and its analogues exhibit paradoxical actions in T2D, acting as both pathogenic and protective effects. While preclinical and limited clinical studies support their role in improving metabolic control, concerns about amyloidogenic toxicity persist. Therefore, further robust clinical trials are needed to clarify amylin's long-term safety and optimize its therapeutic potential in T2D management.