The role of chromogranin A cleavage products in onset of type 1 and 2 diabetes

Chromogranin A (CgA) is a pro-hormone widely expressed in neuroendocrine tissues and elevated in both type 1 (T1D) and type 2 diabetes (T2D). Its diverse biological effects arise from proteolytic cleavage into six bioactive peptides: vasostatin I and II (VS-I/II), chromofungin (CHR), pancreastatin (PST), catestatin (CST), WE-14, and serpinin-each exerting distinct and sometimes opposing functions. This review covers current knowledge on the activity, circulating levels, and mechanistic roles of these peptides in diabetes pathogenesis and progression. Evidence indicates contrasting peptide profiles in T1D and T2D: PST levels are elevated in T2D and promote inflammation, gluconeogenesis, and insulin resistance, whereas CST levels are reduced and exert anti-inflammatory and insulin-sensitizing effects. In T1D, CST and VS-I are increased early after diagnosis, with VS-I and WE-14 functioning as autoantigens that drive autoreactive T cell responses. Knockout mouse models further demonstrate that loss of CgA or CST profoundly alters glucose homeostasis, macrophage polarization, catecholamine release, and diabetes susceptibility. Emerging data highlight a complex nerve-immune-endocrine axis through which CgA peptides regulate metabolic and inflammatory pathways. Collectively, CgA-derived peptides represent promising biomarkers and therapeutic targets, though further translational studies remain essential to define their diagnostic and clinical potential.