28 research outputs found

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

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    Aims: To investigate the anorectic effect of Lā€arginine (Lā€Arg) in rodents. Methods: We investigated the effects of Lā€Arg on food intake, and the role of the anorectic gut hormones glucagonā€like peptideā€1 (GLPā€1) and peptide YY (PYY), the Gā€proteinā€coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Results: Oral gavage of Lā€Arg reduced food intake in rodents, and chronically reduced cumulative food intake in dietā€induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. Lā€Arg stimulated GLPā€1 and PYY release in vitro and in vivo. Pharmacological blockade of GLPā€1 and PYY receptors did not influence the anorectic effect of Lā€Arg. Lā€Argā€mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of Lā€Arg suppressed food intake in rats. Conclusions: Lā€Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of Lā€Arg is unlikely to be mediated by GLPā€1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of Lā€Arg suppressed food intake in rats, suggesting that Lā€Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which Lā€Arg suppresses food intake and its utility in the treatment of obesity

    The effects of dual PPARĪ±/Ī³ agonism compared with ACE inhibition in the BTBRob/ob mouse model of diabetes and diabetic nephropathy

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    The leptin-deficient BTBRob/ob mouse develops progressive albuminuria and morphological lesions similar to human diabetic nephropathy (DN), although whether glomerular hyperfiltration, a recognized feature of early DN that may contribute to renal injury, also occurs in this model is not known. Leptin replacement has been shown to reverse the signs of renal injury in this model, but in contrast, the expected renoprotection by angiotensin-converting enzyme (ACE) inhibition in BTBRob/ob mice seems to be limited. Therefore, to investigate the potential renal benefits of improved metabolic control in this model, we studied the effect of treatment with the dual peroxisome proliferator-activated receptor (PPAR) Ī±/Ī³ agonist AZD6610 and compared it with the ACE inhibitor enalapril. AZD6610 lowered plasma glucose and triglyceride concentrations and increased liver size, but had no significant effect in reducing albuminuria, whereas enalapril did have an effect. Nephrin and WT1 mRNA expression decreased in the kidneys of BTBRob/ob mice, consistent with podocyte injury and loss, but was unaffected by either drug treatment: at the protein level, both nephrin and WT1-positive cells per glomerulus were decreased. Mesangial matrix expansion was reduced in AZD6610-treated mice. GFR, measured by creatinine clearance, was increased in BTBRob/ob mice, but unaffected by either treatment. Unexpectedly, enalapril-treated mice showed intrarenal arteriolar vascular remodeling with concentric thickening of vessel walls. In summary, we found that the BTBRob/ob mouse model shows some similarities to the early changes seen in human DN, but that ACE inhibition or PPARĪ±/Ī³ agonism afforded limited or no kidney protection

    Lā€arginine promotes gut hormone release and reduces food intake in rodents

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    Aims: To investigate the anorectic effect of Lā€arginine (Lā€Arg) in rodents. Methods: We investigated the effects of Lā€Arg on food intake, and the role of the anorectic gut hormones glucagonā€like peptideā€1 (GLPā€1) and peptide YY (PYY), the Gā€proteinā€coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Results: Oral gavage of Lā€Arg reduced food intake in rodents, and chronically reduced cumulative food intake in dietā€induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. Lā€Arg stimulated GLPā€1 and PYY release in vitro and in vivo. Pharmacological blockade of GLPā€1 and PYY receptors did not influence the anorectic effect of Lā€Arg. Lā€Argā€mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of Lā€Arg suppressed food intake in rats. Conclusions: Lā€Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of Lā€Arg is unlikely to be mediated by GLPā€1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of Lā€Arg suppressed food intake in rats, suggesting that Lā€Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which Lā€Arg suppresses food intake and its utility in the treatment of obesity
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