title: CCK increases the transport of insulin into the brain.
abstract: Food intake occurs in bouts or meals, and numerous meal-generated signals have been identified that act to limit the size of ongoing meals. Hormones such as cholecystokinin (CCK) are secreted from the intestine as ingested food is being processed, and in addition to aiding the digestive process, they provide a signal to the brain that contributes to satiation, limiting the size of the meal. The potency of CCK to elicit satiation is enhanced by elevated levels of adiposity signals such as insulin. In the present experiments we asked whether CCK and insulin interact at the level of the blood-brain barrier (BBB). We first isolated rat brain capillary endothelial cells that comprise the BBB and found that they express the mRNA for both the CCK1R and the insulin receptor, providing a basis for a possible interaction. We then administered insulin intraperitoneally to another group of rats and 15min later administered CCK-8 intraperitoneally to half of those rats. After another 15min, CSF and blood samples were obtained and assayed for immunoreactive insulin. Plasma insulin was comparably elevated above baseline in both the CCK-8 and control groups, indicating that the CCK had no effect on circulating insulin levels given these parameters. In contrast, rats administered CCK had CSF-insulin levels that were more than twice as high as those of control rats. We conclude that circulating CCK greatly facilitates the transport of insulin into the brain, likely by acting directly at the BBB. These findings imply that in circumstances in which the plasma levels of both CCK and insulin are elevated, such as during and soon after meals, satiation is likely to be due, in part, to this newly-discovered synergy between CCK and insulin.
authors: University of Cincinnati College of Medicine, Department of Pathology and Molecular Medicine, Metabolic Diseases Institute, OH, USA.
authors: Aaron A
authors: AA
authors: May
authors: University of Cincinnati College of Medicine, Department of Pathology and Molecular Medicine, Metabolic Diseases Institute, OH, USA.
authors: Min
authors: M
authors: Liu
authors: University of Cincinnati College of Medicine, Department of Psychiatry and Behavioral Neuroscience, Metabolic Diseases Institute, OH, USA. Electronic address: steve.woods@uc.edu.
authors: Stephen C
authors: SC
authors: Woods
authors: University of New South Wales, School of Psychology, Sydney, NSW 2052, Australia.
authors: Denovan P
authors: DP
authors: Begg
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology*; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D043886:Receptor, Cholecystokinin A / Q000235:genetics / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology*
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D012844:Sincalide
keywords: Blood-brain barrier; CCK-8; CNS insulin transport; Cholecystokinin receptor; Endocrinology; Satiation