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Activation of nucleus accumbens μ-opioid receptors enhances the response to a glycaemic challenge
Journal of Neuroendocrinology ( IF 3.2 ) Pub Date : 2021-08-26 , DOI: 10.1111/jne.13036
Laura L Koekkoek 1, 2, 3 , Tess Kool 1, 2, 3 , Leslie Eggels 1, 2, 3 , Luna L van der Gun 1, 2, 3 , Khalid Lamuadni 1, 2, 3 , Margo Slomp 1, 2, 3 , Charlene Diepenbroek 1, 2, 3 , Mireillle J Serlie 2 , Andries Kalsbeek 1, 2, 4 , Susanne E la Fleur 1, 2, 3
Affiliation  

Opioids are known to affect blood glucose levels but their exact role in the physiological control of glucose metabolism remains unclear. Although there are numerous studies investigating the peripheral effects of opioid stimulation, little is known about how central opioids control blood glucose and which brain areas are involved. One brain area possibly involved is the nucleus accumbens because, as well as being a key site for opioid effects on food intake, it has also been implicated in the control of blood glucose levels. Within the nucleus accumbens, μ-opioid receptors are most abundantly expressed. Therefore, in the present study, we investigated the role of μ-opioid receptors in the nucleus accumbens in the control of glucose metabolism. We show that infusion of the μ-opioid receptor agonist [d-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) in the nucleus accumbens by itself does not affect blood glucose levels, but it enhances the glycaemic response after both an insulin tolerance test, as well as a glucose tolerance test. These findings indicate that the nucleus accumbens plays a role in the central effects of opioids on glucose metabolism, and highlight the possibility of nucleus accumbens μ-opioid receptors as a therapeutic target for enhancing the counter-regulatory response.

中文翻译:

伏隔核μ-阿片受体的激活增强了对血糖挑战的反应

已知阿片类药物会影响血糖水平,但它们在葡萄糖代谢生理控制中的确切作用仍不清楚。尽管有许多研究调查阿片类药物刺激的外周效应,但对中枢阿片类药物如何控制血糖以及涉及哪些大脑区域知之甚少。一个可能涉及的大脑区域是伏隔核,因为它不仅是阿片类药物影响食物摄入的关键部位,还与血糖水平的控制有关。在伏隔核内,μ-阿片受体最丰富地表达。因此,在本研究中,我们研究了伏隔核中μ-阿片受体在控制葡萄糖代谢中的作用。我们表明输注 μ-阿片受体激动剂 [ d -Ala2 , N -MePhe 4 , Gly-ol]-enkephalin (DAMGO) 在伏隔核中本身不影响血糖水平,但在胰岛素耐量试验和葡萄糖耐量试验后均能增强血糖反应。这些发现表明伏隔核在阿片类药物对葡萄糖代谢的中枢作用中发挥作用,并突出了伏隔核μ-阿片类药物受体作为增强反调节反应的治疗靶点的可能性。
更新日期:2021-10-15
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