Catecholamine storage vesicles and the metabolic syndrome: The role of the chromogranin A fragment pancreastatin.
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.
Zhang
Kuixing
K
Department of Medicine, University of California at San Diego, San Diego, California 92093-0838, USA.
Rao
Fangwen
F
Wen
Gen
G
Salem
Rany M
RM
Vaingankar
Sucheta
S
Mahata
Manjula
M
Mahapatra
Nitish R
NR
Lillie
Elizabeth O
EO
Cadman
Peter E
PE
Friese
Ryan S
RS
Hamilton
Bruce A
BA
Hook
Vivian Y
VY
Mahata
Sushil K
SK
Taupenot
Laurent
L
O'Connor
Daniel T
DT
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D053379:Chromogranin A / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D006801:Humans; D024821:Metabolic Syndrome / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010187:Pancreatic Hormones / Q000235:genetics / Q000502:physiology*; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D016415:Sequence Alignment
D001786:Blood Glucose; D002395:Catecholamines; D053379:Chromogranin A; D010187:Pancreatic Hormones; C050836:pancreastatin