Endocrine Abstracts

Somatostatin (SST), Cortistatin (CORT), ghrelin, and their corresponding receptors (ssts and GHS-R) are closely interrelated systems involved in the regulation of essential hormones for metabolic homeostasis, like insulin, whose release is inhibited by SST/CORT and stimulated by ghrelin. To investigate the underlying mechanisms of this insulin regulation, we analyzed the expression of such systems at pancreatic level in wild type (WT) and CORT knock-out mice (CORT-KO) under both normal, low fat (LF) and high fat (HF) diets. Pancreatic tissue was processed for either direct RNA isolation or islet culture, and expression of distinct components of SS/CORT/ghrelin systems was analyzed by quantitative RT-PCR. Results reveal that SST, ghrelin and their receptors are expressed in both whole pancreas and endocrine islets of WT and CORT-KO mice, being their expression levels variable depending upon the peptide and receptor subtype analyzed. CORT expression was not detected in neither whole nor endocrine pancreas of WT-mice. SST levels remain unaltered in obese animals (HF), while ghrelin expression increased exclusively in WT obese mice. When the expression of the systems analyzed was compared between WT and CORT-KO mice, we found that expression levels of ghrelin, GHS-R, ghrelin o-acyl-transferase (GOAT) and insulin (In-2) were significantly reduced in obese mice. Interestingly, blood insulin levels were significantly lower in CORT-KO than those of WT animals. Taken together, our data reveal that key components of the SST/ghrelin/receptors systems are tightly regulated in the pancreas of WT and CORT-KO under normal and obesity conditions, suggesting that both systems may play a relevant role at the endocrine pancreas under normal physiological conditions and/or in response to extreme metabolic conditions (obesity). Moreover, the fact that circulating insulin levels are significantly diminished in CORT-KO mice strongly suggests that endogenous CORT is an important modulator of pancreatic function.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.