Control of food intake and energy expenditure by amylin-therapeutic implications.
Amylin is a pancreatic B-cell hormone that plays an important role in the control of nutrient fluxes because it reduces food intake, slows gastric emptying, and reduces postprandial glucagon secretion. These actions seem to depend on a direct effect on the area postrema (AP). Subsequent to area AP activation, the amylin signal is conveyed to the forebrain via distinct relay stations. Within the lateral hypothalamic area, amylin diminishes the expression of orexigenic neuropeptides. Recent studies suggest that amylin may also play a role as a long term, adiposity signal. Similar to leptin or insulin, an infusion of amylin into the brain resulted in lower body weight gain than in controls, irrespective of the starting body weight. Interestingly, preliminary data also suggest that rats fed an energy-dense diet develop resistance to central amylin. In addition to amylin's action to control meal termination and to act as a potential adiposity signal, amylin and its agonist salmon calcitonin have recently been shown to increase energy expenditure under certain conditions. In summary, amylin may be an interesting target as a body weight lowering drug. In fact, recent studies provide evidence that amylin, especially when combined with other anorectic hormones (for example, peptide YY and leptin) has beneficial long-term effects on body weight.
Lutz
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Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich, Winterthurerstrasse 260, Zurich, Switzerland. tomlutz@vetphys.uzh.ch
D050154:Adiposity / Q000187:drug effects / Q000502:physiology; D000682:Amyloid / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D031608:Area Postrema / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D006801:Humans; D058228:Islet Amyloid Polypeptide; D020738:Leptin / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy; D019894:Peptide YY / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D012528:Satiety Response / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
D000682:Amyloid; D001067:Appetite Depressants; D058228:Islet Amyloid Polypeptide; D020738:Leptin; D016760:Proto-Oncogene Proteins c-fos; D019894:Peptide YY