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1 Introduction
Pancreastatin (PST) is a regulatory peptide with multiple effects on the general
metabolism. And even though the physiological role for PST has not yet been com-
pletely elucidated, there is no doubt about its importance in both endocrine and
exocrine secretion, as well as in the regulation of energy metabolism. The counter-
regulatory action of PST on insulin signaling has been described many times in
different systems, such as in rat hepatoma cells or adipocytes.
The present chapter aims to compile the current knowledge about PST, including
the biological origin of the peptide, its synthesis and secretion, as well as its action
and the underlying molecular mechanisms in liver and adipose tissues.
1.1 Structure, Processing and Secretion
The biologically active peptide PST was first isolated from porcine pancreas in
1986, as a 49 aa (51 kDa) chain with no homology with any other gastrointestinal
hormone (Tatemoto et al. 1986 ). Almost immediately, PST presence was found in
neuroendocrine and gastrointestinal tissues, and in 1987 the origin of the peptide
was already determined. PST was found to be the proteolytic product of chromo-
granin A (CGA), an acidic glycoprotein ubiquitously present in the secretory gran-
ules of the sympathetic adrenal system (Eiden 1987 ; Konecki et al. 1987 ; Schmidt
et al. 1988 ; Tatemoto and Mutt 1978 ; Huttner and Benedum 1987 ; Winkler and
Fischer-Colbrie 1992 ). Today it is well-known that CGA processing produces a
variety of regulatory peptides, but PST was the first one to be described (Taupenot
et al. 2003 ).
1.1.1 Pancreastatin Structure
Primary Structure
Despite of the fact that PST is a unique peptide with no evident homology to other
peptide family, it shares the poly-glutamate sequence with gastrin and the COOH-
terminal Arg-Gly-NH2 with vasopressin, being the amidated C-terminus a common
feature among many regulatory peptides from the neuroendocrine system (Tatemoto
et al. 1986 ). In fact, this part of the molecule is the responsible of its biological
activity (Tatemoto et al. 1986 ; Zhang et al. 1990 ).
Another interesting point is that among all the CGA derived peptides, PST is the
only one conserved exclusively in mammals, with no homology with any other
vertebrates. In addition, a 41.5% homology exists between the human and the
Tasmanian devil, and being these species so highly separated in the phylogenetic
tree, it may indicate its importance in early mammalian evolution. This homology is
N.E. Evtikhova et al.