Effects of amylin-related peptides on food intake,  meal patterns, and gastric emptying in rats

Reidelberger, Roger D.; Kelsey, Linda; Heimann, Dean G.

doi:10.1152/ajpregu.00597.2001

Cited by 61 publications

(56 citation statements)

References 56 publications

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“…Consistent among reports of amylin on feeding microstructure is the finding that meal size is virtually always reduced, and this effect occurs at lower doses than the effects on other feeding variables. 3,[24][25][26] In the present study, amylin also tended to increase meal latency, however, this effect did not achieve statistical significance.…”

Section: Discussioncontrasting

confidence: 91%

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

Roth¹,

Trevaskis²,

Wilson³

et al. 2008

Int J Obes

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Objective: To characterize the interactive effects of amylin with phentermine or sibutramine on food intake, body weight/ composition and gene expression in diet-induced obese (DIO) rats. Design: DIO rats were intraperitoneally injected with a single dose of amylin (10 mg kg À1 ) and/or phentermine (1 mg kg À1 ) or chronically infused with amylin (100 mg kg À1 d À1 ) or vehicle with or without phentermine (0.5-10 mg kg À1 d À1 ) or sibutramine (3 mg kg À1 d À1 ) using two surgically implanted subcutaneous osmotic mini-pumps. Measurements: Twenty-four hour food intake, locomotor activity and components of meal microstructure (meal size, latency, duration and intermeal interval) were measured following acute administration (amylin, phentermine or amylin þ phentermine). Body weight and composition (for amylin and/or sibutramine or phentermine) and metabolism-related gene mRNA expression in the liver (fatty acid synthase, stearoyl-CoA desaturase-1 and carnitine palmitoyltransferase-1) and brown fat (b-adrenergic receptors and uncoupling protein-1) were measured (for amylin and/or phentermine) after sustained infusion (2 weeks). Results: Acute co-administration of amylin (10 mg kg À1 ) and phentermine (1 mg kg À1 ) reduced acute food intake (up to 19 h) more than either monotherapy. In two studies, sustained subcutaneous infusion of amylin for 2 weeks decreased cumulative food intake (22%) and vehicle-corrected body weight gain (B4-8%). Phentermine's anorexigenic (10-17%) and weightreducing effects (B0-5%) were only evident at the highest dose tested (10 mg kg À1 d À1 ). Combination of amylin (100 mg kg À1 d À1 ) and phentermine reduced food intake (30-43%), body weight (8-12%) and adiposity to a greater extent than either monotherapy. Amylin prevented phentermine-induced reductions in UCP-1 mRNA in brown adipose tissue. When amylin þ sibutramine were infused, mathematically additive decreases in food intake (up to 45%) and body weight (up to 12%) were evident. Similar to amylin þ phentermine treatment, amylin þ sibutramine mediated weight loss was attributable to significant reductions in fat mass. Conclusions: Combined treatment of DIO rats with the pancreatic b-cell hormone amylin and phentermine or sibutramine resulted in additive anorexigenic, weight-and fat-reducing effects.

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Section: Discussioncontrasting

confidence: 91%

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

Roth¹,

Trevaskis²,

Wilson³

et al. 2008

Int J Obes

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“…Our results also suggest that hPYY(3-36) and rPYY , which differ by two amino acids at positions 3 and 18 (20,28), inhibit gastric emptying in rats with a similar potency and efficacy. We have used the same experimental model to determine the dose-dependent effects of CCK-8, amylin, calcitonin (CT), salmon CT (sCT), CT-gene-related peptide (CGRP), and adrenomedullin (ADM) on gastric emptying (41,42). Our results suggest an order of potency of sCT Ͼ amylin Ͼ CCK-8 ϭ PYY(3-36) Ͼ CGRP ϭ ADM Ͼ PYY(1-36) Ͼ CT (estimated ED 50 s are 1, 3, 35, 37, 130, 160, 470, and 730 pmol⅐kg Ϫ1 ⅐min Ϫ1 , respectively).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Chelikani

Haver²,

Reidelberger³

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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We compared the effects of the two molecular forms of the brain-gut peptide YY (PYY), PYY(1-36) and PYY(3-36), on gastric emptying. Unanesthetized rats received 20-min intravenous infusions of rat PYY(1-36) (0, 1.7, 5, 17, 50, 100, 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and rat PYY(3-36) (0, 0.5, 1.7, 5, 17, 50, 100, 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ), either alone or combined, and gastric emptying of saline was measured during the last 10 min of infusion. For comparison, human PYY(3-36) was administered at 0, 17, and 50 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 . Gastric emptying was decreased by 11, 24, 26 and 38% in response to 17, 50, 100, and 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of rat PYY(1-36); by 10, 26, 41, 53, and 57% in response to 5, 17, 50, 100, and 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of rat PYY(3-36); and by 35 and 53% in response to 17 and 50 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of human PYY(3-36), respectively. Estimated ED50s were 470 and 37 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 for rat PYY(1-36) and PYY(3-36), respectively. In general, within an experiment, coadministration of PYY(1-36) and PYY(3-36) inhibited gastric emptying by an amount that was comparable to that produced when either peptide was given alone. We conclude that 1) intravenous infusion of PYY(1-36) and PYY(3-36) each produces a dose-dependent inhibition of gastric emptying in rats, 2) PYY(3-36) is an order of magnitude more potent than PYY(1-36) in inhibiting gastric emptying, 3) human PYY(3-36) and rat PYY(3-36) inhibit gastric emptying similarly, and 4) PYY(1-36) and PYY(3-36) do not appear to interact in an additive or synergistic manner to inhibit gastric emptying. intravenous infusion; dose response; interaction PEPTIDE YY (PYY), neuropeptide Y (NPY), and pancreatic polypeptide (PP) comprise the "PP-fold" family of structurally related brain-gut peptides. PYY is synthesized in the gastrointestinal tract, as well as in the central and peripheral nervous systems. Endocrine cells of the ileum, colon, and rectum provide a major source of PYY (2, 47). PYY has also been detected in gastric mucosa, pancreatic islets, myenteric and serosal ganglia, sympathetic neurons, adrenal gland, spinal cord, and brain, including the hypothalamus, pituitary, pons, medulla oblongata, and the brain stem (7-9, 15, 16, 22, 30, 32, 37).Food intake releases PYY into the circulation (2, 47). Systemic administration of PYY inhibits food intake, gastric emptying, intestinal fluid and electrolyte secretion, gallbladder contraction, and exocrine pancreatic secretion (5, 36). Whether PYY acts physiologically by endocrine, neurocrine, and/or paracrine mechanisms to produce these effects remains to be determined. If PYY acts as a blood-borne hormonal signal to produce an effect, then it is important to determine whether the effect is produced by intravenous doses of PYY that reproduce meal-induced increases in plasma PYY.The two major molecular forms of PYY found in the gut and circulation are PYY(1-36) and PYY(3-36) (19 -21). In humans, plasma concentrations of PYY were reported to be 11 pM in the fasted state with PYY(3-36) contributing 37% ...

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“…We have provided evidence that CCK, GLP-1, PYY , and amylin may inhibit food intake in part by inhibiting gastric emptying because each peptide dose-dependently reduces food intake and gastric emptying with similar potency and efficacy in rats (3)(4)(5)(6). Ghrelin has been reported to stimulate both gastric emptying and food intake (2,7,8).…”

Section: 2mentioning

confidence: 98%

Ghrelin Attenuates the Inhibitory Effects of Glucagon-Like Peptide-1 and Peptide YY(3-36) on Food Intake and Gastric Emptying in Rats

2006

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Ghrelin stimulates, while glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) [PYY(3-36)] inhibit, food intake and gastric emptying in rats. We determined the dose-dependent effects of a 3-h intravenous infusion of ghrelin at dark onset on food intake in freely feeding rats, and on the inhibitory effects of intravenous infusion of GLP-1 and PYY(3-36) on food intake and gastric emptying. Ghrelin (150 pmol ⅐ kg ؊1 ⅐ min ؊1 ) stimulated food intake by 28% during the infusion period primarily by increasing meal frequency; doses of 15 and 50 pmol ⅐ kg ؊1 ⅐ min ؊1 had no effect. GLP-1 (15 pmol ⅐ kg ؊1 ⅐ min ؊1 ) inhibited food intake by 35-54%; coinfusion of ghrelin at 50 and 150 pmol ⅐ kg These results suggest that ghrelin may stimulate food intake in part by attenuating the inhibitory effects of GLP-1 and PYY(3-36) on gastric emptying and food intake.

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Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats

Cited by 61 publications

References 56 publications

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Ghrelin Attenuates the Inhibitory Effects of Glucagon-Like Peptide-1 and Peptide YY(3-36) on Food Intake and Gastric Emptying in Rats

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