CCK increases the transport of insulin into the brain

PHYSIOLOGY & BEHAVIOR

卷:165

Article

May, Aaron A.¹  Liu, Min¹  Woods, Stephen C.²  Begg, Denovan P.³ 

[1] Univ Cincinnati, Coll Med, Dept Pathol & Mol Med, Metab Dis Inst, Cincinnati, OH 45221 USA

[2] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Metab Dis Inst, Cincinnati, OH 45221 USA

[3] Univ New South Wales, Sch Psychol, Sydney, NSW 2052, Australia

关键词: Blood-brain barrier;    Cholecystokinin receptor;    CNS insulin transport;    Satiation;    Endocrinology;    CCK-8;   

DOI  :  10.1016/j.physbeh.2016.08.025

来源: Elsevier

【 摘 要 】

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 15 min later administered CCK-8 intraperitoneally to half of those rats. After another 15 min, 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. (C) 2016 Elsevier Inc. All rights reserved.

【 授权许可】

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