Gaetano Felice Caldara

Glucagon-like peptide-2 treatment improves glucose dysmetabolism in mice fed a high-fat diet

Previous studies suggested that endogenous glucagon-like peptide 2 (GLP-2) is dispensable for the regulation of glucose homeostasis under normal conditions, while it can play a beneficial role in obesity conditions. The purpose of the present study was to investigate whether chronic treatment with Gly2-GLP-2, a stable analogue of GLP-2, can have an impact on glycaemic and lipid control in mice fed a high-fat diet (HFD), an animal model of human obesity and insulin resistance. HFD mice were treated once a day with Gly2-GLP-2 for 4xa0weeks. Body weight, food intake, fasting glucose, intraperitoneal glucose tolerance, insulin-induced glucose clearance, glucose-stimulated insulin secretion, β-cell mass, plasma lipid metabolic profile, and lipid deposition in the liver were examined. In untreated HFD mice, fasting glucose levels, glucose tolerance, glucose-stimulated plasma insulin and sensibility to exogenous insulin were deteriorating with time and β-cell mass increased. In Gly2-GLP-2-treated mice, we found significant increase in glucose tolerance and exogenous insulin sensitivity, reduction in glucose-stimulated plasma insulin and in the increase in β-cell mass in comparison with pair-aged HFD untreated animals. The chronic treatment with the peptide was not associated with remarkable improvements of dyslipidemia and it did not prevent liver fat accumulation and the presence of microvesicular steatosis. In conclusion, the results of the present study suggest, for the first time, that Gly2-GLP-2 may produce glucose metabolic benefits in mice with diet-induced obesity. The mechanisms underlying the beneficial impact of GLP-2 on glucose metabolism remain to be established.

Chronic administration of green tea extract to TRAMP mice induces the collapse of Golgi apparatus in prostate secretory cells and results in alterations of protein post-translational processing

Considering its long latency, prostate cancer (PCa) represents an ideal target for chemoprevention strategies. Green tea extract (GTE) has been proved to be one of the most promising natural substances capable of inhibiting PCa progression in animal models (transgenic adenocarcinoma of mouse prostate), as well as in humans. However, the cellular targets of the GTE action are mostly unknown. The main objective of this work was to investigate whether the endoplasmic reticulum (ER) and the Golgi apparatus (GA), known to be actively involved in sensing stress stimuli and initiating and propagating cell death signalling, may represent the subcellular targets of GTE action. To this end, 42 TRAMP mice were divided into four experimental groups: groups II and IV, received GTE in tap water (0.3 g/100 ml solution) starting at 8 weeks of age and up to the time of sacrifice. Groups I and III were respective age-matched water-fed controls. The animals were sacrificed after 4 weeks (groups I and II) or 40 weeks of treatment (groups II and IV). We also treated TRAMP-C2 cells with GTE (20 µg/ml for 7 days) to check the expression profile of clusterin (CLU), a protein involved in prostate tumourigenesis, extensively processed through ER-GA before being secreted through the plasma membrane. In vivo we found that chronic administration of GTE in TRAMP mice results in collapse of ER and GA in prostate epithelial cells. Consistently, in vitro we found that the mature, fully processed form of CLU, sCLU, is strongly reduced by GTE treatment in TRAMP-C2 cells. Taking into account the sCLU biogenesis dependence on the ER-GA integrity and the proposed anti-apoptotic role of sCLU, the possibility for GTE to counteract PCa progression by interfering with sCLU biogenesis is suggested.

Adaptive Response of Osteoblasts Grown on a Titanium Surface: Morphology, Cell Proliferation and Stress Protein Synthesis

P. Borghetti1,∗, E. De Angelis1, G. Caldara2, A. Corradi1, A. Cacchioli3 and C. Gabbi3 1Pathology Unit, Department of Animal Health, Faculty of Veterinary Medicine, University of Parma, 43100 Parma, Italy; 2Department of Human Anatomy, Pharmacology and Forensic Medicine, Section of Human Anatomy, Faculty of Medicine, University of Parma, 43100 Parma, Italy; 3Anatomy Unit, Department of Animal Health, Faculty of Veterinary Medicine, University of Parma, 43100 Parma, Italy ∗Correspondence: E-mail: paolo.borghetti@unipr.it

Health benefits of pistachios consumption

Abstract The health benefits of nuts, mainly in relation to the improvement of dysmetabolic conditions such as obesity, type 2 diabetes mellitus and the related cardiovascular diseases, have been widely demonstrated. Compared to other nuts, pistachios have a lower fat and caloric content, and contain the highest levels of unsaturated fatty acids, potassium, γ-tocopherol, phytosterols and xanthophyll carotenoids, all substances that are well known for their antioxidant and anti-inflammatory actions. This variety of nutrients contributes to the growing body of evidence that the consumption of pistachios improves health, leading to a greater potential of healthy antioxidant and anti-inflammatory activity, glycemic control, and endothelial function. The present review examines the nutrients and phytochemicals present in pistachios as well as the potential health benefits of including pistachios in a diet. Mechanisms by which pistachio consumption can positively affect the separate components of Metabolic Syndrome.

Activation of angiotensin II type 1 receptors and contractile activity in human sigmoid colon in vitro

To analyse the effects of angiotensin II (Ang II) on the contractility of human sigmoid colon, and to characterize the subtype(s) of receptor(s) involved and the related action mechanism.

Neuronostatin: peripheral site of action in mouse stomach.

Neuronostatin is a 13-amino acid peptide encoded by somatostatin gene. It is distributed in different organs including gastrointestinal tract and has been involved in the control of food intake and gastrointestinal motility, likely through an action in the brain. So far, there are no reports about the occurrence of peripheral action sites in the gut. Therefore, the purpose of the present study was to examine, in the mouse, the effects of peripheral administration of neuronostatin on food intake within 24h and on gastrointestinal motility and to analyse neuronostatin actions on the gastric and intestinal mechanical activity in isolated preparations in vitro. When compared with PBS-treated mice, intraperitoneal neuronostatin reduced food intake in doses ranging from 1 to 15ng/g b.w. only in the first hour postinjection with a maximum effect obtained at the dose of 15ng/g b.w. (-46.9%). The peptide (15ng/g b.w.) significantly reduced gastric emptying rate (-31.1%) and gastrointestinal intestinal transit. Non-amidated neuronostatin failed to affect food intake, gastric emptying and intestinal transit, suggesting the specificity of action. In vitro, neuronostatin induced concentration-dependent gastric relaxation, which was abolished by tetrodotoxin. Neuronostatin failed to affect the spontaneous mechanical activity or the evoked cholinergic contractions in duodenum. These results suggest that exogenous neuronostatin is able to reduce mouse gastric motility by acting peripherally in the stomach, through intramural nervous plexuses. This indirectly action could cause reduction of food intake in the short term.

Postnatal development of the dopaminergic signaling involved in the modulation of intestinal motility in mice

Background:Since antidopaminergic drugs are pharmacological agents employed in the management of gastrointestinal motor disorders at all ages, we investigated whether the enteric dopaminergic system may undergo developmental changes after birth.Methods:Intestinal mechanical activity was examined in vitro as changes in isometric tension.Results:In 2-d-old (P2) mice, dopamine induced a contractile effect, decreasing in intensity with age, replaced, at the weaning (day 20), by a relaxant response. Both responses were tetrodotoxin (TTX)-insensitive. In P2, dopaminergic contraction was inhibited by D1-like receptor antagonist and mimicked by D1-like receptor agonist. In 90-d-old (P90) mice, the relaxation was reduced by both D1- and D2-like receptor antagonists, and mimicked by D1- and D2-like receptor agonists. In P2, contraction was antagonized by phospholipase C inhibitor, while in P90 relaxation was antagonized by adenylyl cyclase inhibitor and potentiated by phospholipase C inhibitor. The presence of dopamine receptors was assessed by immunofluorescence. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed a significant increase in D1, D2, and D3 receptor expression in proximal intestine with the age.Conclusion:In mouse small intestine, the response to dopamine undergoes developmental changes shifting from contraction to relaxation at weaning, as the consequence of D2-like receptor recruitment and increased expression of D1 receptors.

Pancreatic polypeptide stimulates mouse gastric motor activity through peripheral neural mechanisms

Pancreatic polypeptide (PP) is supposed to be one of the major endogenous agonists of the neuropeptide Y4 receptor. Pancreatic polypeptide can influence gastrointestinal motility, acting mainly through vagal mechanisms, but whether PP acts directly on the stomach has not been explored yet. The aims of this study were to investigate the effects of PP on mouse gastric emptying, on spontaneous tone of whole stomach in vitro and to examine the mechanism of action.

Angiotensin II type II receptors and colonic dysmotility in 2,4-dinitrofluorobenzenesulfonic acid-induced colitis in rats

Angiotensin II (Ang II), the main peptide of the renin‐angiotensin system (RAS), has been suggested to be involved in inflammatory bowel diseases. Since RAS has emerged as gut motility regulator, and dysmotility is associated with intestinal inflammation, our objective was to investigate in rat 2,4‐dinitrobenzenesulfonic acid (DNBS)‐induced colitis the functionality of RAS and its contribution to colonic motor alterations.

Differential recruitment of Angiotensin II receptors in the modulation of rat colonic contractile activity in experimental inflammation

Characterization of the effects of the antineoplastic drug 5-fluorouracil on gastrointestinal motility and gut wall structure in the rat R. ABALO*, I. P EREZ-GARC IA, G. VERA, Ma D. R. GIR ON, M. MART IN-FONTELLES, A. E. L OPEZP EREZ and J. A. URANGA *Pharmacology and Nutrition, Universidad Rey Juan Carlos, Alcorc on, Spain, Universidad Rey Juan Carlos, Alcorc on, Spain and Hospital Gregorio Mara~ n on, Alcorc on, SpainActivation of 5-HT4 receptors present on porcine enteric cholinergic neurons enhances ongoing cholinergic activity and smooth muscle contraction; the signaling pathway of the 5-HT4 receptors in the cholinergic neurons is controlled by phosphodiesterase 4 (PDE). The presence of 5-HT4 receptors on murine cholinergic neurons innervating the enteric smooth muscle layer and the possible control by PDEs was now investigated.