Article

TLQP-21, a VGF-derived peptide, stimulates exocrine pancreatic secretion in the rat

Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Rome, Italy.
Peptides (Impact Factor: 2.61). 04/2012; 36(1):133-6. DOI: 10.1016/j.peptides.2012.03.035
Source: PubMed

ABSTRACT The aims of this paper were to study: (1) the effects of TLQP-21 (non-acronic name), the C-terminal region of the VGF (non-acronic name), polypeptide (from residue 557 to 576 of VGF), on in vitro amylase release from rat isolated pancreatic lobules and acinar cells; (2) the mechanism through which TLQP-21 regulates exocrine pancreatic secretion, by using the muscarinic receptor antagonist atropine (10(-6)M) and the cyclo-oxygenase inhibitor, indomethacin (10(-6)M). On pancreatic lobules of rats, concentrations of TLQP-21 from 10(-7) to 10(-5)M significantly (p<0.05) induced a 2-3-fold increase of baseline pancreatic amylase release, measured at the end of 60 min incubation period. Co-incubation with atropine 10(-6)M did not antagonise the enzyme outflow induced by the peptide. On the contrary, co-incubation of TLQP-21 (10(-7) and 10(-6)M) with indomethacin, at concentration of 10(-6)M, which alone did not modify enzyme secretion, completely suppressed the increase of amylase evoked by TLQP-21 on pancreatic lobules. On rat pancreatic acinar cells, TLQP-21, at all the concentrations tested, was unable to affect exocrine pancreatic secretion, indicating an indirect mechanism of action on acinar cells. These results put in evidence, for the first time, that TLQP-21, a VGF-derived peptide, modulates exocrine pancreatic secretion in rats through a stimulatory mechanism involving prostaglandin release. In conclusion, TLQP-21 could be included among the neurohumoral signals regulating pancreatic exocrine secretion, and increases the knowledge concerning the systems controlling this function.

Download full-text

Full-text

Available from: Carla Petrella, Jun 21, 2015
1 Follower
 · 
186 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hyperglycemia causes oxidative stress that could damage vascular endothelial cells, leading to cardiovascular complications. The Vgf gene was identified as a nerve growth factor-responsive gene, and its protein product, VGF, is characterized by the presence of partially cleaved products. One of the VGF-derived peptides is TLQP-21, which is composed of 21 amino acids (residues 556-576). Past studies have reported that TLQP-21 could stimulate insulin secretion in pancreatic cells and protect these cells from apoptosis, which suggests that TLQP-21 has a potential function in diabetes therapy. Here, we explore the protective role of TLQP-21 against the high glucose-mediated injury of vascular endothelial cells. Using human umbilical vascular endothelial cells (HUVECs), we demonstrated that TLQP-21 (10 or 50 nM) dose-dependently prevented apoptosis under high-glucose (30 mmol/L) conditions (the normal glucose concentration is 5.6 mmol/L). TLQP-21 enhanced the expression of NAPDH, resulting in upregulation of glutathione (GSH) and a reduction in the levels of reactive oxygen species (ROS). TLQP-21 also upregulated the expression of glucose-6-phosphate dehydrogenase (G6PD), which is known as the main source of NADPH. Knockdown of G6PD almost completely blocked the increase of NADPH induced by TLQP-21, indicating that TLQP-21 functions mainly through G6PD to promote NADPH generation. In conclusion, TLQP-21 could increase G6PD expression, which in turn may increase the synthesis of NADPH and GSH, thereby partially restoring the redox status of vascular endothelial cells under high glucose injury. We propose that TLQP-21 is a promising drug for diabetes therapy.
    PLoS ONE 11/2013; 8(11):e79760. DOI:10.1371/journal.pone.0079760 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: VGF (non-acronymic), a protein expressed in the hypothalamus and pituitary, is involved in the control of metabolism and body weight homeostasis. Different active peptide fragments are generated from VGF, including TLQP-21. Previous studies of our group reported that this molecule participates also in the regulation of reproductive function in male rats, with predominant stimulatory effects. Methods: We report herein a series of studies on the reproductive effects of TLQP-21 in female rats, as evaluated by a combination of in vivo and in vitro analyses. Results: TLQP-21 modestly increased serum LH levels after systemic administration and directly stimulated pituitary LH and FSH secretion in prepubertal female rats, while acute central injection of TLQP-21 was unable to modify LH secretion at this age. Repeated central administration of TLQP-21 during the pubertal transition (between PND 28-35) to female rats fed ad libitum advanced the timing of vaginal opening and increased the percentage of animals with signs of ovulation. Moreover, an analogous treatment slightly enhanced ovarian maturation in pubertal female rats subjected to chronic undernutrition, but was unable to rescue the delay of vaginal opening induced by food deprivation. In addition, TLQP-21 oppositely modified LH secretion in adult female rats depending on the stage of the ovarian cycle: it stimulated LH secretion when injected in the morning of diestrus and decreased the magnitude of the preovulatory LH (but not FSH) surge when injected in the afternoon of proestrus. Conclusions: Our data are the first to document the potential involvement of TLQP-21 in the control of reproductive function in female rats.
    Neuroendocrinology 03/2013; 98(1). DOI:10.1159/000350323 · 4.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: TLQP-21, a peptide derived from VGF (non-acronymic) by proteolytic processing has been shown to modulate energy metabolism, differentiation and cellular response to stress. Although extensively investigated, the receptor for this endogenous peptide has not previously been described. This report describes the use of a series of studies that show G protein-coupled receptor (GPCR)-mediated biological activity of TLQP-21 signalling in CHO-K1 cells. Unbiased genome wide sequencing of the transcriptome from responsive CHO-K1 cells identified a prioritized list of possible GPCRs bringing about this activity. Further experiments using a series of defined receptor antagonists as well as siRNAs led to the identification of the complement receptor C3AR1 as a target for TLQP-21 in rodents. We have not been able to demonstrate so far that this finding is translatable to the human receptor. Our results are in line with a large number of physiological observations in rodent models of food intake and metabolic control, where TLQP-21 shows activity. In addition, the sensitivity of TLQP-21 signalling to pertussis toxin is consistent with the known signalling pathway of the C3AR1 receptor. The binding of TLQP-21 to the C3AR1 not only has effects on signalling but it also modulates cellular functions as TLQP-21 was shown to have a role in directing migration of RAW264.7 mouse cells.
    Journal of Biological Chemistry 08/2013; DOI:10.1074/jbc.M113.497214 · 4.60 Impact Factor