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gluconeogenesis, by the inhibition of the insulin signaling (Gayen et al. 2009 ;
Valicherla et al. 2013 ).
All these data suggest that PST could be an important regulator of hepatic glu-
cose metabolism, by cross-talk with the insulin signaling pathway.
3.2 In Adipocytes
In a similar way to the mechanism of PST action described in hepatocytes, PST
action in rat adipocytes is also mediated by the activation of PLC-β3, mainly through
the Gαq/11 family of G proteins (Gonzalez-Yanes et al. 1999 ), and to a lesser extent
via the Gαi1,2 protein (Sanchez-Margalet et al. 2010 ). Therefore, trough PLC-β 3
pathway signaling, PST stimulates the translocation of classical PKC isoform to the
plasma membrane. Then, PKC may mediate MAPK activation (Gonzalez-Yanes
and Sanchez-Margalet 2000 ). In this way, the calcium-PKC signaling is responsible
for the PST inhibition of glucose transport, glycogen synthesis, leptin expression,
and the activation of lipolysis (Gonzalez-Yanes and Sanchez-Margalet, 2000 , 2001 ,
2003 ), whereas the PST stimulation of protein synthesis in the adipocyte is medi-
ated by the MAPK pathway, and the activation the translation initiation machinery
(Gonzalez-Yanes and Sanchez-Margalet 2002 ). In this context, PKC activated
through Gq/11 has been shown to stimulate MAPK by a Ras-independent, Raf-1
dependent, Ser- phosphorylation (Kolch et al. 1993 ). Consequently, we determined
that PST stimulates both basal and insulin stimulated p42/44-MAPK activity trough
Tyr/Thr phosphorylation (Gonzalez-Yanes and Sanchez-Margalet 2000 ). On the
other hand, the initiation factor eIF-4E and 4E–BP1, which helps to liberate eIF-4E,
are phosphorylated and activated in presence of PST (Gonzalez-Yanes and Sanchez-
Margalet 2002 ). In conclusion, PST signaling in adipocytes, has two important
pathways: the PLC- β3 signaling regulating the energy storage and MAPK/eIF-4E
regulating protein synthesis. Thus, PLC signaling is the molecular mechanism
underlying the PST regulation of adipose tissue metabolism.
4 The Pancreastatin Receptor
There is no final conclusion to identify the specific receptor through which PST is
working. We have try out to purify this receptor from liver cells with no success. A
possible explanation could be that the interaction between ligand and receptor is too
labile to be maintained during the current elution process. But, in rat liver plasma
membranes, we have carry out the purification of the active PST receptor by cova-
lent cross linking and gel filtration study, identifying a ~85 kDa glycoprotein that
specifically bound with the wheat-germ agglutinin (WGA) lectin. In addition, the
fact that the eluted protein has sensitivity to Pertussis Toxin (PT) suggest that the
N.E. Evtikhova et al.