Orosco M, Rouch C, Gripois D, Blouquit M F, Roffi J, Jacquot C, Cohen Y
Université Paris-Sud, URA-CNRS 594, Laboratoire de Pharmacologie, Faculté de Pharmacie, Châtenay-Malabry, France.
Psychoneuroendocrinology. 1991;16(6):537-46. doi: 10.1016/0306-4530(91)90037-t.
Disturbances of insulin or brain monoamine metabolism may play a role in the impaired regulation of food intake and body weight in the obese Zucker rat. We investigated a possible insulin-monoamine interaction by measuring monoamine levels in the hypothalamus and striatum of obese (fa-fa) and lean (Fa-Fa and Fa-fa) Zucker rats after peripheral insulin administration. The classically reported effects of insulin, i.e., increases in tryptophan, 5-hydroxy-indolacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC) levels, were observed in the hypothalamus of Fa-Fa and Fa-fa rats, but not in obese fa-fa rats. Given the mechanism of action of insulin, this lack of effect in the obese rats may be related to the peripheral insulin resistance they exhibit. Furthermore, given the role of these monoaminergic systems, this reduced effect may be related to the impaired regulation of food intake and body weight. At 8 wk of age, however, insulin restored the decreased basal 5-HIAA levels observed in the obese rats. Increase in 5-HIAA levels following insulin administration appeared in the striatum of Fa-Fa rats only, suggesting that, as for brain insulin content, other central insulin-related disturbances may be related to the presence of the "fa" gene. In addition, certain effects of insulin on striatal dopamine release were observed in only the Fa-Fa and fa-fa rats, suggesting a particular disturbance related to the heterozygous character. This latter point calls for further investigations on the central dopaminergic effects of insulin.
胰岛素或脑单胺代谢紊乱可能在肥胖的 Zucker 大鼠食物摄入和体重调节受损中起作用。我们通过测量外周注射胰岛素后肥胖（fa-fa）和瘦（Fa-Fa 和 Fa-fa）Zucker 大鼠下丘脑和纹状体中的单胺水平，研究了胰岛素 - 单胺之间可能的相互作用。在 Fa-Fa 和 Fa-fa 大鼠的下丘脑中观察到了胰岛素经典报道的作用，即色氨酸、5-羟吲哚乙酸（5-HIAA）和二羟基苯乙酸（DOPAC）水平升高，但在肥胖的 fa-fa 大鼠中未观察到。鉴于胰岛素的作用机制，肥胖大鼠中这种缺乏效应可能与它们表现出的外周胰岛素抵抗有关。此外，鉴于这些单胺能系统的作用，这种效应减弱可能与食物摄入和体重调节受损有关。然而，在 8 周龄时，胰岛素恢复了肥胖大鼠中观察到的基础 5-HIAA 水平降低。胰岛素给药后 5-HIAA 水平升高仅出现在 Fa-Fa 大鼠的纹状体中，这表明，就脑胰岛素含量而言，其他与中枢胰岛素相关的紊乱可能与“fa”基因的存在有关。此外，仅在 Fa-Fa 和 fa-fa 大鼠中观察到胰岛素对纹状体多巴胺释放的某些影响，这表明存在与杂合特征相关的特定紊乱。后一点需要对胰岛素的中枢多巴胺能效应进行进一步研究。
