Effect of CCK-8 on insulin-induced hyperphagia and hypothalamic orexigenic neuropeptide expression in the rat.
The influence of cholecystokinin octapeptide (CCK-8) on normal and insulin-induced feeding and expression of orexigenic hypothalamic neuropeptides was investigated in male rats. CCK-8, administered during meals (4 microg/kg) or continuously (32 microg/kg over 60 min), blunted the stimulating effect of insulin (50 IU/kg) on feeding by reducing meal size (-60%; P<0.05 or -86%; P<0.0001, respectively). Rats without access to food and injected with IP insulin (50 IU/kg) showed increased hypothalamic mRNA levels of orexin (+30%; P<0.05) and melanin-concentrating hormone (+52%; P<0.05), as compared with ad libitum-fed and saline-injected control rats. Continuous IP infusion of CCK-8 (32 microg/kg) blunted these increases. Our results suggest that both orexin and melanin-concentrating hormone participate in the response to insulin hypoglycemia without food being present; these neurons may be involved in mechanisms related to insulin-induced hyperphagia. Signals triggered by peripheral CCK-8 act to decrease the expression of orexin and melanin-concentrating hormone. This may be associated with a reduction in hyperphagia.
Gallmann
Eva
E
Physiology and Animal Husbandry, Institute of Animal Sciences, Swiss Federal Institute of Technology, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Arsenijevic
Denis
D
Spengler
Marianne
M
Williams
Gareth
G
Langhans
Wolfgang
W
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005247:Feeding Behavior; D006963:Hyperphagia / Q000188:drug therapy*; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D008297:Male; D008543:Melanins / Q000378:metabolism; D009479:Neuropeptides / Q000096:biosynthesis* / Q000737:chemistry; D000068797:Orexins; D010907:Pituitary Hormones / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response; D012844:Sincalide / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D007028:Hypothalamic Hormones; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D012333:RNA, Messenger; C019463:melanin-concentrating hormone; D012844:Sincalide