26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is upregulated in obese animal models, and its orexigenic activity is accentuated in rodents fed a highfat diet, suggesting that this neuropeptide might play a role in the development and maintenance of the obese status. As obesity is frequently associated with type 2 diabetes, we investigated whether 26RFa may be involved in the regulation of glucose homeostasis. In the current study, we show a moderate positive correlation between plasma 26RFa levels and plasma insulin in patients with diabetes. Plasma 26RFa concentration also increases in response to an oral glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103 are present in human pancreatic b-cells as well as in the gut. In mice, 26RFa attenuates the hyperglycemia induced by a glucose load, potentiates insulin sensitivity, and increases plasma insulin concentrations. Consistent with these data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we show, using in vivo and in vitro approaches, that a glucose load induces a massive secretion of 26RFa by the small intestine. Altogether, the present data indicate that 26RFa acts as an incretin to regulate glucose homeostasis.26RFa and its N-extended form 43RFa (also referred to as QRFPs) are RFamide peptides discovered in the brain of various vertebrate species and identified as the cognate ligands of the human orphan G-protein-coupled receptor GPR103 (1-6). Neuroanatomical observations revealed that 26RFa-and GPR103-expressing neurons are primarily localized in hypothalamic nuclei involved in the control of feeding behavior (1,2,5,7). Indeed, intracerebroventricular administration of 26RFa or 43RFa stimulates food intake (1,5,8,9), and the neuropeptide exerts its orexigenic activity by modulating the neuropeptide Y/proopiomelanocortin system in the arcuate nucleus (9). Chronic injection of 43RFa induces a significant increase in mice body weight and fat mass, which is associated with a hyperphagic behavior (8), and the orexigenic activities of 26RFa and 43RFa are more robust in rodents fed a high-fat diet (8,10). Consistent with these observations, expression of prepro26RFa mRNA is upregulated in the hypothalamus of genetically obese ob/ob and db/db mice and rodents subjected to a high-fat diet (5,10). Altogether, these observations support the notion that 26RFa could play a role in the development and maintenance of the obese status.Obesity is frequently associated with type 2 diabetes, which is characterized by chronic hyperglycemia induced by impaired insulin secretion and increased insulin resistance (11-13). Accumulating evidence supports the
Background: Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) are known to be involved in various diseases related to inflammation, vascular remodeling, or growth deregulation. In addition, increases in plasma concentrations of these cytokines appear to provide useful diagnostic and prognostic information. We therefore investigated which factors most strongly influence the biological variations of plasma IL-8, MCP-1, EGF, and VEGF concentrations. Methods: We used the Evidence ® biochip array analyzer to quantify plasma IL-8, MCP-1, EGF, and VEGF concentrations in a subsample of 304 children (age range, 4 -17 years) and 540 adults (age range, 18 -55 years) from the STANISLAS family study. We also calculated reference intervals for the 4 cytokines. Results: We found the following associations with plasma marker concentrations: Age, neutrophil count, and glucose concentration were positively associated with IL-8 concentrations in children and adults, as were smoking and platelet count in adults. MCP-1 concentrations were associated with age and smoking in both children and adults, monocyte count in children, and sex and hematocrit in adults. EGF concentrations were
This mini-review deals with the neuropeptide 26RFa (or QRFP) which is a member of the RFamide peptide family discovered simultaneously by three groups in 2003. 26RFa (or its N-extended form 43RFa) was subsequently shown to be the endogenous ligand of the human orphan receptor GPR103. In the brain, 26RFa and GPR103mRNA are primarily expressed in hypothalamic nuclei involved in the control of feeding behavior, and at the periphery, the neuropeptide and its receptor are present in abundance in the gut and the pancreatic islets, suggesting that 26RFa is involved in the regulation of energy metabolism. Indeed, 26RFa stimulates food intake when injected centrally, and its orexigenic effect is even more pronounced in obese animals. The expression of 26RFa is up-regulated in the hypothalamus of obese animals, supporting that the 26RFa/GPR103 system may play a role in the development and/or maintenance of the obese status. Recent data indicate that 26RFa is also involved in the regulation of glucose homeostasis. 26RFa reduces glucose-induced hyperglycemia, increases insulin sensitivity and insulinemia. Furthermore, an oral ingestion of glucose strongly stimulates 26RFa release by the gut, indicating that 26RFa is a novel incretin. Finally, 26RFa is able to prevent pancreatic β cell death and apoptosis. This brief overview reveals that 26RFa is a key neuropeptide in the regulation of energy metabolism. Further fields of research are suggested including the pathophysiological implication of the 26RFa/GPR103 system.
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