Amylin receptors mediate the anorectic action of salmon calcitonin (sCT)

Lutz, Thomas; Tschudy, S; Rushing, Paul A.; Scharrer, E.

doi:10.1016/s0196-9781(99)00208-9

Cited by 78 publications

(95 citation statements)

References 32 publications

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“…Acute administration of amylin and phentermine Consistent with previous reports, 3,4 amylin decreased the size of the first meal consumed after administration (Table 1; Po0.05 vs vehicle). Phentermine did not significantly affect meal size, latency, duration or the satiety ratio (calculated as the intermeal interval divided by the meal size).…”

Section: Resultssupporting

confidence: 89%

“…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: 89%

“…Several groups have described the acute anorexigenic effects and analysis of meal microstructure following a peripheral injection of amylin. 3,4 In line with these findings, amylin's anorexigenic effects in the present studies were most evident shortly after injection, followed by a rebound in food intake most likely due to the relatively short half-life (B13 min) 22,23 and/or compensatory responses related to negative energy balance. Analyses of meal microstructure revealed that amylin primarily reduced food intake by decreasing meal size.…”

Section: Discussionsupporting

confidence: 87%

“…In rodents, acute administration of amylin reduced meal size. 3,4 Chronic peripheral infusion of amylin to lean or diet-induced obese (DIO) rats decreased food intake and body weight. [5][6][7][8][9] These preclinical findings concerning the antiobesity effects of amylin agonism have been confirmed in various clinical studies.…”

Section: Introductionmentioning

confidence: 99%

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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: Resultssupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 89%

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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show abstract

“…Endogenous amylin and its analogue and receptor agonist, salmon calcitonin (sCT), exert anorexigenic properties by signalling satiation (Lutz et al 1995;Lutz et al 2000;Reidelberger et al 2004;Mack et al 2007;Lutz 2012). Amylin receptors have been identified in various brain areas including area postrema, nucleus of the solitary tract and dorsal raphe among others (Sexton et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

2018

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Alcohol expresses its reinforcing properties by activating areas of the mesolimbic dopamine system, which consists of dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens. The findings that reward induced by food and addictive drugs involve common mechanisms raise the possibility that gut-brain hormones, which control appetite, such as amylin, could be involved in reward regulation. Amylin decreases food intake, and despite its implication in the regulation of natural rewards, tenuous evidence support amylinergic mediation of artificial rewards, such as alcohol. Therefore, the present experiments were designed to investigate the effect of salmon calcitonin (sCT), an amylin receptor agonist and analogue of endogenous amylin, on various alcohol-related behaviours in rodents. We showed that acute sCT administration attenuated the established effects of alcohol on the mesolimbic dopamine system, particularly alcohol-induced locomotor stimulation and accumbal dopamine release. Using the conditioned place preference model, we demonstrated that repeated sCT administration prevented the expression of alcohol's rewarding properties and that acute sCT administration blocked the reward-dependent memory consolidation. In addition, sCT pre-treatment attenuated alcohol intake in low alcohol-consuming rats, with a more evident decrease in high alcohol consumers in the intermittent alcohol access model. Lastly, sCT did not alter peanut butter intake, blood alcohol concentration and plasma corticosterone levels in mice. Taken together, the present data support that amylin signalling is involved in the expression of alcohol reinforcement and that amylin receptor agonists could be considered for the treatment of alcohol use disorder in humans.

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Systemic and Central Amylin, Amylin Receptor Signaling, and Their Physiological and Pathophysiological Roles in Metabolism

Foll

Lutz

2020

Comprehensive Physiology

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This article in the Neural and Endocrine Section of Comprehensive Physiology discusses the physiology and pathophysiology of the pancreatic hormone amylin. Shortly after its discovery in 1986, amylin has been shown to reduce food intake as a satiation signal to limit meal size. Amylin also affects food reward, sensitizes the brain to the catabolic actions of leptin, and may also play a prominent role in the development of certain brain areas that are involved in metabolic control. Amylin may act at different sites in the brain in addition to the area postrema (AP) in the caudal hindbrain. In particular, the sensitizing effect of amylin on leptin action may depend on a direct interaction in the hypothalamus. The concept of central pathways mediating amylin action became more complex after the discovery that amylin is also synthesized in certain hypothalamic areas but the interaction between central and peripheral amylin signaling remains currently unexplored. Amylin may also play a dominant pathophysiological role that is associated with the aggregation of monomeric amylin into larger, cytotoxic molecular entities. This aggregation in certain species may contribute to the development of type 2 diabetes mellitus but also cardiovascular disease. Amylin receptor pharmacology is complex because several distinct amylin receptor subtypes have been described, because other neuropeptides [e.g., calcitonin gene-related peptide (CGRP)] can also bind to amylin receptors, and because some components of the functional amylin receptor are also used for other G-protein coupled receptor (GPCR) systems.

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Amylin receptors mediate the anorectic action of salmon calcitonin (sCT)

Cited by 78 publications

References 32 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

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

Systemic and Central Amylin, Amylin Receptor Signaling, and Their Physiological and Pathophysiological Roles in Metabolism

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