Secretin (Sct) is released into the circulation postprandially from the duodenal S-cells. The major functions of Sct originated from the gastrointestinal system are to delay gastric emptying, stimulate fluid secretion from pancreas and liver, and hence optimize the digestion process. In recent years, Sct and its receptor (Sctr) have been identified in discrete nuclei of the hypothalamus, including the paraventricular nucleus (PVN) and the arcuate nucleus (Arc). These nuclei are the primary brain sites that are engaged in regulating body energy homeostasis, thus providing anatomical evidence to support a functional role of Sct in appetite control. In this study, the effect of Sct on feeding behavior was investigated using wild-type (wt), Sct(-/-), and secretin receptor-deficient (Sctr(-/-)) mice. We found that both central and peripheral administration of Sct could induce Fos expression in the PVN and Arc, suggesting the activation of hypothalamic feeding centers by this peptide. Consistent with this notion, Sct was found to increase thyrotropin-releasing hormone and melanocortin-4 receptor (Mc4r) transcripts in the PVN, and augment proopiomelanocortin, but reduces agouti-related protein mRNA expression in the Arc. Injection of Sct was able to suppress food intake in wt mice, but not in Sctr(-/-) mice, and that this effect was abolished upon pretreatment with SHU9119, an antagonist for Mc4r. In summary, our data suggest for the first time that Sct is an anorectic peptide, and that this function is mediated by the melanocortin system.

Body fluid homeostasis is critical for the survival of living organisms and hence is tightly controlled. From initial studies on the effects of secretin (SCT) on renal water reabsorption in the 1940s and recent investigations of its role in cardiovascular and neuroendocrine functions, it has now become increasingly clear that this peptide is an integral component of the homeostatic processes that maintain body fluid balance. This review, containing some of our recent findings of centrally expressed SCT on water intake, focuses on the actions of SCT in influencing the physiological, neuroendocrine, and cardiovascular processes that subserve body fluid homeostasis.

The maintenance of body water homeostasis depends on the balance between water intake and water excretion. In the kidney, vasopressin (Vp) is a critical regulator of water homeostasis by controlling the insertion of aquaporin 2 (AQP2) onto the apical membrane of the collecting duct principal cells in the short term and regulating the gene expression of AQP2 in the long term. A growing body of evidence from both in vitro and in vivo studies demonstrated that both secretin and oxytocin are involved as Vp-independent mechanisms regulating the renal water reabsorption process, including the translocation and expression of AQP2. This review focuses on how these two hormones are potentially involved as Vp-independent mechanisms in controlling water homeostasis.

Secretin (SCT) is a classical peptide hormone that is synthesized and released from the gastrointestinal tract after a meal. We have previously shown that it acts both as a central and peripheral anorectic peptide, and that its central effect is mediated via melanocortin system. As peripheral satiety signals from the gastrointestinal tract can be sent to the brain via the vagal afferent or by crossing the blood-brain barrier (BBB), we therefore sought to investigate the pathway by which peripheral SCT reduces appetite in this study. It is found that bilateral subdiaphragmatic vagotomy and treatment of capsaicin, an excitotoxin for primary afferent neurons, could both block the anorectic effect of peripherally injected SCT. These treatments are found to be capable of blunting i.p. SCT-induced Fos activation in pro-opiomelanocortin (POMC) neurons within the hypothalamic Arcuate Nucleus (Arc). Moreover, we have also found that bilateral midbrain transaction could block feeding reduction by peripheral SCT. Taken together, we conclude that the satiety signals of peripheral SCT released from the gastrointestinal tract are sent via the vagus nerves to the brainstem and subsequently Arc, where it controls central expression of other regulatory peptides to regulate food intake.

2016-12-23T18:49:38