Chromogranins or
secretogranins (
granins), present in secretory granules of virtually all neuroendocrine cells and neurones, are structurally related
proteins encoded by different genetic loci:
chromogranins A and B, and
secretogranins II through VI. Compelling evidence supports both intracellular and extracellular functions for this
protein family. Within the cells of origin, a granulogenic or sorting role in the regulated pathway of
hormone or
neurotransmitter secretion has been documented, especially for
chromogranin A (CHGA).
Granins also function as pro-
hormones, giving rise by proteolytic processing to an array of
peptide fragments for which diverse autocrine, paracrine, and endocrine activities have been demonstrated. CHGA measurements yield insight into the pathogenesis of such human diseases as
essential hypertension, in which deficiency of the
catecholamine release-inhibitory CHGA fragment
catestatin may trigger sympathoadrenal overactivity as an aetiologic culprit in the syndrome. The CHGA dysglycaemic fragment
pancreastatin is functional in humans in vivo, affecting both
carbohydrate (
glucose) and
lipid (
fatty acid) metabolism.
Pancreastatin is cleaved from CHGA in
hormone storage granules in vivo, and its plasma concentration varies in human disease. The
pancreastatin region of CHGA gives rise to three naturally occurring human variants, one of which (Gly297Ser) occurs in the functionally important carboxy-terminus of the
peptide, and substantially increases the
peptide's potency to inhibit cellular
glucose uptake. These observations establish a role for
pancreastatin in human intermediary metabolism and disease, and suggest that qualitative hereditary alterations in
pancreastatin's primary structure may give rise to interindividual differences in
glucose disposition.