Original ArticlesSynergy between amylin and cholecystokinin for inhibition of food intake in mice
Section snippets
Animals
Male Swiss–Webster (NIH-Swiss) mice (n = 378) obtained from Harlan (Madison, WI, USA) at 6 to 8 weeks of age were housed in groups of four. Body mass was 29.3 ± 1.9 g (mean ± SD) at the time of experiments. Mice had ad lib. access to water and food pellets (Teklad LM 485, Madison, WI, USA) and were maintained in an environment of 22 ± 1°C, 60 ± 10% relative humidity, 12:12 light:dark cycle (lights on at 0600 hours) for at least 1 week before experiments. All experiments were conducted between
Food intake after injection with amylin or CCK-8 alone
Amylin and CCK-8 each inhibited 30-min food intake in overnight-fasted NIH-Swiss mice in a sigmoid dose-dependent manner (Goodness of fit r2 = 0.996, 0.997, respectively).
Amylin, at the highest dose tested (25.5 nmol/kg; 100μg/kg i.p.), reduced food intake by 57.0 ± 5.6% (p < 0.01 cf. saline injected controls). The ED50 for amylin-inhibition of food intake was 0.93 nmol/kg (3.63 μg/kg) ± 0.34 log units. The least effective dose of amylin (the lowest dose producing a response different from
Discussion
We have shown that both amylin and CCK-8 dose-dependently inhibit food intake in the overnight fasted mice, when injected i.p., confirming previous reports that these peptides reduce food intake. CCK, which circulates in man at concentrations of 1–7 pm (19), is proposed to be an endogenous peripheral satiety agent. Some (25) have argued that amylin, which circulates at concentrations of 5–25 pm (28) could also function, in part, as an endogenous satiety agent.
Amylin’s action to inhibit gastric
References (36)
- et al.
Syntheses, structures and anorectic effects of human and rat amylin
Peptides
(1991) - et al.
Permeability of the blood-brain barrier to amylin
Life Sci
(1995) The expected effect of a combination of agentsthe general solution
J. Theor. Biol.
(1985)- et al.
Anorexia following the intrahypothalamic administration of amylin
Brain Res
(1991) - et al.
Anorexia following the systemic injection of amylin
Brain Res
(1993) - et al.
Tests of adipsia and conditioned taste aversion following the intrahypothalamic injection of amylin
Peptides
(1992) - et al.
Combined injection potentiates the satiety effects of pancreatic glucagon, cholecystokinin, and bombesin
Brain Res. Bull.
(1986) - et al.
Increased insulin responses to ingested foods are associated with lessened satiety
Appetite
(1995) - et al.
Reduction of food intake in rats by i.p. injection of low doses of amylin
Physiol. Behav.
(1994) - et al.
Subdiaphragmatic vagotomy does not influence the anorectic effect of amylin
Peptides
(1995)
Amylin decreases meal size in rats
Physiol. Behav.
Amylin decreases food intake in mice
Peptides
Central insulin enhances sensitivity to cholecystokinin
Physiol. Behav.
Structure and biology of amylin
Trends Pharmacol. Sci.
The evaluation of insulin as a metabolic signal influencing behavior via the brain
Neurosci. Biobehav. Rev.
High affinity amylin binding sites in rat brain
Mol. Pharmacol.
Inhibition of gastric emptying and of food intake appear to be independently controlled in rodents
Soc. Neurosci. Abstr.
Cited by (106)
Effects of pramlintide on energy intake and food preference in rats given a choice diet
2021, Physiology and BehaviorCitation Excerpt :We only observed a reduction in HFD intake after pramlintide injection at one timepoint, with no longer term effects on HFD intake, energy intake, preference for HFD, or on daily weight change. This is in contrast to the previous literature examining acute administration of amylin into the periphery, which has been shown to reduce both food intake and body weight in mice [18, 45] and rats [46-49]. Additionally, our results contrast with evidence that systemic oral administration of pramlintide reduces chow intake and body weight in mice [23] and that systemic amylin reduces preference for HFD in rats given a choice diet [50].
Natural and Drug Rewards Engage Distinct Pathways that Converge on Coordinated Hypothalamic and Reward Circuits
2019, NeuronCitation Excerpt :It has recently been shown that these signals rapidly and robustly reduce AgRP neuron activity (Beutler et al., 2017; Su et al., 2017). CCK and PYY are thought to act at least in part through action on the vagus nerve, which in turn rapidly transmits GI signals to the brain (Bhavsar et al., 1998; Kopin et al., 1999; Neary et al., 2005). Additionally, PYY has been shown to act directly on AgRP neurons (Batterham et al., 2002).
Cholecystokinin (CCK) and related adjunct peptide therapies for the treatment of obesity and type 2 diabetes
2018, PeptidesCitation Excerpt :In this regard, administration of amylin and CCK-8 was shown to synergistically reduce food intake by 91% overnight fasted mice [75]. Indeed, when pharmacologically ineffective doses of amylin and CCK were combined in mice, this elicited a near-maximal inhibitory effect on feeding [75]. Similar synergistic inhibitory actions on appetite were observed after dual administration of CCK and amylin in goldfish [76].