L-Arginine promotes gut hormone release and reduces food intake in rodents

Aims The amino acids generated by protein digestion may play a role in the weight loss driven by high protein diets. We investigated the anorectic effect of L-arginine (L-Arg) in rodents. Materials and Methods We investigated the effect of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Results Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice or subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (ICV) and intraperitoneal (IP) administration of L-Arg suppressed food intake in rats. Conclusions L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. ICV and IP administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act upon the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity

l-cysteine suppresses ghrelin and reduces appetite in rodents and humans.

24.03.15 KB. OK to add published version to spiral, OA pape

The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases

The Ca2+-sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and β-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid hormone secretion, urinary Ca2+ excretion, skeletal development and lactation. The importance of the CaSR for these calcitropic processes is highlighted by loss-of-function and gain-of-function CaSR mutations that cause familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, respectively, and also by the fact that alterations in parathyroid CaSR expression contribute to the pathogenesis of primary and secondary hyperparathyroidism. Moreover, the CaSR is an established therapeutic target for hyperparathyroid disorders. The CaSR is also expressed in organs not involved in Ca2+ homeostasis: it has noncalcitropic roles in lung and neuronal development, vascular tone, gastrointestinal nutrient sensing, wound healing and secretion of insulin and enteroendocrine hormones. Furthermore, the abnormal expression or function of the CaSR is implicated in cardiovascular and neurological diseases, as well as in asthma, and the CaSR is reported to protect against colorectal cancer and neuroblastoma but increase the malignant potential of prostate and breast cancers

Development of a technique to minimise the wind-induced noise in shielded microphones

S.V. Alamshah, A.C.Zander, V.V. Lenchinehttp://www.acoustics.asn.au/conference_proceedings/AAS2013/papers/AAS2013-Information.pdfhttp://www.acoustics.asn.au/conference_proceedings/AAS2013

Prosthetic hemodialysis access-induced distal hand ischemia and its contributors in diabetics

Avoidance of hand ischemia in the construction of prosthetic access for hemodialysis in diabetics that have no suitable vein for arteriovenous fistula is appreciated. Taper type may be an appropriately matched conduit to prevent its occurrence. This is a prospective controlled trial of 38 selected diabetics requiring hemodialysis, who were referred to our clinic during a period of 6 months. The aim of the study was to evaluate the efficacy of tapered grafts in preventing distal hand hypoperfusion and determining its most likely contributors. In 18 intervening cases, taper 4 mm × 7 mm and in twenty cases (control group), standard 6 mm polytetrafluoroethylene as straight Brachial-Axillary access was used. Graft flow rates, artery and vein diameters, and mean arterial pressure were included for evaluation. Within the control group, 11 patients (55%) (7 cases Grade 1, 3 Grade 2, 1 Grade 3) and in intervening group, 2 cases (11%) (Grade 1, Grade 3) developed Steal syndrome. There was no significant difference in the mean flow rates (P = 0.82). Increased risk of distal hypoperfusion was observed in the control group when flow rates were more than 1000 ml/min. Arterial diameters (P = 0.011) and mean arterial pressure (P = 0.05) were found to be important contributing factors. Taper grafts causes reduced incidence of distal hand hypoperfusion. When artery diameter was <6 mm and mean arterial pressure lower than 100 mmHg and the index (brachial artery diameter × mean arterial pressure) was under 500, distal hand ischemia occurred in standard and tapper type. We therefore recommend selective usage of taper grafts in diabetics with diminished distal hand pulses, considering the contributing factors when fistula first is not feasible

L-Arginine increases post-prandial circulating GLP-1 and PYY levels in humans

Objective The satiating effect of protein compared with other nutrients has been well described and is thought to be mediated, in part, by gut hormone release. Previously, it has been shown that oral L‐arginine acts as a GLP‐1 secretagogue both in vitro and in vivo in rodents. Here, the effect of L‐arginine on gut hormone release in humans was investigated. Methods The hypothesis was tested in two separate studies. The first study assessed the tolerability of oral L‐arginine in healthy human subjects. The second study assessed the effect of oral L‐arginine on gut hormone release following an ad libitum meal. Subjects were given L‐arginine, glycine (control amino acid), or vehicle control in a randomized double‐blind fashion. Results At a dose of 17.1 mmol, L‐arginine was well tolerated and stimulated the release of plasma GLP‐1 (P < 0.05) and PYY (P < 0.001) following an ad libitum meal. Food diaries showed a trend toward lower energy intake and particularly fat intake following L‐arginine treatment. Conclusions L‐arginine can significantly elevate GLP‐1 and PYY in healthy human volunteers in combination with a meal. Further work is required to investigate whether L‐arginine may have utility in the suppression of appetite and food intake

The homeostatic dynamics of feeding behaviour identify novel mechanisms of anorectic agents

Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analysing the different effects on feeding behaviour of PYY3-36, lithium chloride, GLP-1 and leptin shows the precise behavioural changes caused by each anorectic agent. Our analysis demonstrates that the changes in feeding behaviour evoked by the anorectic agents investigated do not mimic the behaviour of well-fed animals, and that the intermeal interval is influenced by fullness. We show how robust homeostatic control of feeding thwarts attempts to reduce food intake, and how this might be overcome. In silico experiments suggest that introducing a minimum intermeal interval or modulating upper gut emptying can be as effective as anorectic drug administration

GPRC6a is not required for the effects of a high‐protein diet on body weight in mice

Objective: The G-protein coupled receptor family C group 6 member A (GPRC6A) is activated by proteinogenic amino acids and may sense amino acids in the gastrointestinal tract and the brain. The study investigated whether GPRC6A was necessary for the effects of low- and high-protein diets on body weight and food intake in mice. Methods: The role of GPRC6A in mediating the effects of a low-protein diet on body weight was investi-gated in GPRC6a knockout (GPRC6a-KO) and wild-type (WT) mice fed a control diet (18 % protein) or a low-protein diet (6 % protein) for 9 days. The role of GPRC6A in mediating the effects of a high-protein diet on body weight was investigated in GPRC6a-KO and WT mice fed a control diet (18 % protein) or a high-protein diet (50 % protein) for 5 weeks. Results: A high-protein diet reduced body weight gain and food intake compared with a control diet in both WT and GPRC6a-KO mice. A low-protein diet decreased body weight gain in GPRC6a-KO mice. Conclusions: GPRC6A was not necessary for the effects of a low- or high-protein diet on body weight and likely does not play a role in protein-induced satiety