Implications of Amylin Receptor Agonism

Roth, Jonathan D.; Maier, Holly; Chen, Steve; Roland, Barbara

doi:10.1001/archneurol.2008.581

Cited by 47 publications

(27 citation statements)

References 35 publications

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“…Though a significant attenuation of the intake-suppressive effects is not observed until the 24h timepoint, these data are comparable to a similar experiment performed in the VTA (35) in which effects were also only observed at 24h. In contrast to the VTA and LDTg, previous reports have shown that systemically delivered amylin agonists are able to activate AP amylin receptors more rapidly (22, 43). Thus, there appears to be a temporal difference in systemic amylin agonists’ action in distributed nuclei throughout the neuraxis that requires further investigation.…”

Section: Discussionmentioning

confidence: 86%

“…Amylin activates its receptors within the CNS to suppress ongoing feeding during the meal and increase satiation (21, 22). Historically, the contribution of central amylin signaling to food intake control has centered on its action in homeostatic feeding centers, primarily the area postrema (AP) of the caudal brainstem (23–30), and secondarily in hypothalamic subnuclei including the arcuate nucleus (ARH) and ventromedial hypothalamus (VMH) (31–33).…”

Section: Introductionmentioning

confidence: 99%

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Amylin Acts in the Lateral Dorsal Tegmental Nucleus to Regulate Energy Balance Through Gamma-Aminobutyric Acid Signaling

Reiner¹,

Mietlicki‐Baase²,

Olivos³

et al. 2017

Biological Psychiatry

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Background The pancreatic- and brain-derived hormone amylin promotes negative energy balance and is receiving increasing attention as a promising obesity therapeutic. However, the neurobiological substrates mediating amylin’s effects are not fully characterized. We postulated that amylin acts in the lateral dorsal tegmental nucleus (LDTg), an understudied neural-processing hub for reward and homeostatic feeding signals. Methods We used immunohistochemical (IHC) and quantitative PCR analyses to examine expression of the amylin receptor complex in rat LDTg tissue. Behavioral experiments were performed to examine the mechanisms underlying the hypophagic effects of amylin receptor activation in the LDTg. Results IHC and quantitative PCR analyses show expression of the amylin receptor complex in the LDTg. Activation of LDTg amylin receptors by the agonist salmon calcitonin dose-dependently reduces body weight, food intake, and motivated feeding behaviors. Acute pharmacological studies and longer-term adeno-associated viral (AAV)-knockdown experiments indicate that LDTg amylin receptor signaling is physiologically and potentially pre-clinically relevant for energy balance control. Finally, IHC data indicate that LDTg amylin receptors are expressed on gamma-aminobutyric acid (GABA)-ergic neurons and behavioral results suggest that local GABA receptor signaling mediates the hypophagia following LDTg amylin receptor activation. Conclusions These findings identify the LDTg as a novel nucleus with therapeutic potential in mediating amylin’s effects on energy balance through GABA receptor signaling.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Amylin Acts in the Lateral Dorsal Tegmental Nucleus to Regulate Energy Balance Through Gamma-Aminobutyric Acid Signaling

Reiner¹,

Mietlicki‐Baase²,

Olivos³

et al. 2017

Biological Psychiatry

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“…islet amyloid polypeptide; IAPP), a 37 amino acid peptide that is co-secreted with insulin and also plays a role in the regulation of blood glucose and other physiological functions (104; 139; 159). Amylin’s secretion is also modulated in part by the presence of nutrients in the GI tract, however unlike incretin hormones, amylin’s ability to modulate glycemic control is not thought to be a result of potentiated insulin release.…”

Section: Incretin- and Amylin-mediated Signaling In Blood Glucose mentioning

confidence: 99%

“…pramlintide, salmon calcitonin (sCT)] are among the most widely studied of amylin’s multiple physiological functions [see (104; 107; 158; 159) for review]. Indeed, the amylin analog, pramlintide, is FDA-approved for the treatment of both type 1 and type 2 diabetes mellitus.…”

Section: Amylin Regulation Of Blood Glucose and Energy Intakementioning

confidence: 99%

“…Accordingly, the amylin system is a potentially attractive target for the pharmacological treatment of obesity due to its anorectic actions. The intake-inhibitory effects of amylin receptor agonists are mediated by direct action in the brain following stimulation of amylin receptors (104; 107; 158; 159). Amylin receptors are fairly unique in that they contain one of two splice variants of the calcitonin receptor (CTa/CTb; a G-protein coupled receptor) heterodimerized with one of the receptor activity modifying proteins (RAMP1, RAMP2 or RAMP3) [see (150; 157) for review].…”

Section: Amylin Regulation Of Blood Glucose and Energy Intakementioning

confidence: 99%

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Incretins and Amylin: Neuroendocrine Communication Between the Gut, Pancreas, and Brain in Control of Food Intake and Blood Glucose

et al. 2014

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Arguably the most fundamental physiological systems for all eukaryotic life are those governing energy balance. Without sufficient energy, an individual is unable to survive and reproduce. Thus, an ever-growing appreciation is that mammalian physiology developed a redundant set of neuroendocrine signals that regulate energy intake and expenditure, which maintains sufficient circulating energy, predominantly in the form of glucose, to ensure that energy needs are met throughout the body. This orchestrated control requires cross-talk between the gastrointestinal tract which senses the incoming meal, the pancreas which produces glycemic counterregulatory hormones, and the brain which controls autonomic and behavioral processes regulating energy balance. Therefore, this review highlights the physiological, pharmacological, and pathophysiological effects of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), as well as the pancreatic hormone amylin, on energy balance and glycemic control.

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