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Pancreastatin (PST) is one of the regulatory peptides derived from intracellular and/or extracellular processing of chromogranin A, the soluble acidic protein present in the secretory granules of the neuroendocrine system.While the intracellular functions of chromogranin A include formation and maturation of the secretory granule, the major extracellular functions are generation of biologically active peptides with demonstrated autocrine, paracrine or endocrine activities.Many different reported effects have implicated PST in the modulation of energy metabolism, with a general counterregulatory effect to that of insulin.PST induces glycogenolysis in liver and lipolysis in adipocytes.This effect of PST has been confirmed in chromogranin-A knockout mice model.Besides, PST as well as catecholamines may modulate adipocyte differentiation.The metabolic effects of PST have also been found in humans.Moreover, naturally occurring human variants have been found, one of which (Gly297Ser) occurs in the functionally important carboxy-terminus of the peptide, and substantially increases the peptides potency to inhibit cellular glucose uptake.Thus, qualitative hereditary alterations in pancreastatins primary structure may give rise to interindividual differences in glucose and lipid metabolism.PST activates a receptor signaling system that belongs to the seven-spanning transmembrane receptor coupled to a Gq-PLCβ-calcium-PKC signaling pathway.Increased PST plasma levels, correlating with catecholamines levels,have been found in insulin resistance states, such as gestational diabetes or essential hypertension.PST plays important physiological role in potentiating the metabolic effects of catecholamines, including the energy metabolism and the adipocyte differentiation.Therefore, PST may also play a pathophysiological role in insulin resistance states with increased sympathetic activity.