Role of Endogenous Cortistatin in the Regulation of Ghrelin System Expression at Pancreatic Level under Normal and Obese Conditions
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Author
Chanclón García, Belén
Luque, Raúl M.
Córdoba-Chacón, José
Gahete Ortiz, Manuel D.
Pozo-Salas, Ana I.
Castaño, Justo P.
Gracia-Navarro, F.
Martínez-Fuentes, Antonio J.
Publisher
Public Library Of Science (PLOS)Date
2013Subject
Ghrelin-systemPancreas
Endocrinology
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Show full item recordAbstract
Ghrelin-system components [native ghrelin, In1-ghrelin, Ghrelin-O-acyltransferase enzyme (GOAT) and receptors (GHS-Rs)]
are expressed in a wide variety of tissues, including the pancreas, where they exert different biological actions including
regulation of neuroendocrine secretions, food intake and pancreatic function. The expression of ghrelin system is regulated
by metabolic conditions (fasting/obesity) and is associated with the progression of obesity and insulin resistance. Cortistatin
(CORT), a neuropeptide able to activate GHS-R, has emerged as an additional link in gut-brain interplay. Indeed, we recently
reported that male CORT deficient mice (cort2/2) are insulin-resistant and present a clear dysregulation in the stomach
ghrelin-system. The present work was focused at analyzing the expression pattern of ghrelin-system components at
pancreas level in cort2/2 mice and their control littermates (cort +/+) under low- or high-fat diet. Our data reveal that all
the ghrelin-system components are expressed at the mouse pancreatic level, where, interestingly, In1-ghrelin was expressed
at higher levels than native-ghrelin. Thus, GOAT mRNA levels were significantly lower in cort2/2 mice compared with
controls while native ghrelin, In1-ghrelin and GHS-R transcript levels remained unaltered under normal metabolic
conditions. Moreover, under obese condition, a significant increase in pancreatic expression of native-ghrelin, In1-ghrelin
and GHS-R was observed in obese cort+/+ but not in cort2/2 mice. Interestingly, insulin expression and release was
elevated in obese cort+/+, while these changes were not observed in obese cort2/2 mice. Altogether, our results indicate
that the ghrelin-system expression is clearly regulated in the pancreas of cort+/+ and cort 2/2 under normal and/or obesity
conditions suggesting that this system may play relevant roles in the endocrine pancreas. Most importantly, our data
demonstrate, for the first time, that endogenous CORT is essential for the obesity-induced changes in insulin expression/
secretion observed in mice, suggesting that CORT is a key regulatory component of the pancreatic function