視床下部性肥満ラットの膵内分泌機能と自律神経系の役割に関する研究

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Data from laboratolies have indicated that an excess amount of monosodium glutamate (MSG) causes extensive damage to the arcuate nucleus of the hypothalamus of rodents when this agent is given during the suckling period, and that a rodent thus treated subsequently develops obesity and some endocrinological abnormalities. Especially in this study it was aimmed 1) to extend existing observation on MSG-induced obesity and to examine the change of metabolic and pancreatic hormonal patterns in relation to the growing of obesity induced by MSG in Wistar rats, 2) to determine whether the hormonal alterlations observed in MSG-treated rats can be involved the autonomic nervous system. MSG, 2mg per g of body weight, was subcutaneously injected for the 5 consecutive days after the birth. Body weight, Lee index, plasma glucose, triglyceride (TG), immunoreactive insulin (IRI) and glucagon (IRG) were measured at one-month interval during from one to 11 months in male and female rats. Plasma immunoreactive somatostatin (IRS) was also determined at the 7th month or later. All parameters in plasma described above were assayed on samples drawn from the jugular vein. To investigate the role of the autonomic nervous system, subdiaphragmatic vagotomy was performed in male MSG-treated and control rats at the 3rd month. Three months later, arginineinduced IRI and IRS responses were examined in vagotomized and sham-vagotomized animals. Further, responses of IRI and IRS to the intravenous infusion of atropine, methoxamine and isoproterenol were examined in the portal plasma at the 8th month. All parameters in MSG-treated rats were compared with those in age- and sex-matched controls which received the vehicle alone. Plasma IRI was elevated by 54% in MSG pups even at the 1st month. Thereafter, MSG-treated rats showed a progressive increase in plasma IRI. Plasma TG levels were significantly elevated at all ages except the 1st month. Plasma IRG also showed a constant one to two fold elevation irrespective of the duration of obesity. Obese rats induced by MSG had a significant elevation of plasma IRS except the 8th and 11th month in males. Though female MSG-treated rats showed a reduction in body weight for the first 2 months, thereafter they showed a progressive increase throughout the observation. On the other hand, male MSG-treated rats showed a reduction in body weight until the 8th month. The Lee index of obesity increased progressively in both sexes after the 3rd month of age. Among MSG-treated rats, there existed a significant correlation between plasma IRI levels and Lee index. In contrast with the marked changes in plasma IRI, no significant difference in plasma glucose was found between MSG-treated rats and irrespective controls through the entire period of the observation. Subdiaphragmatic vagotomy reversed the increment of body weight and Lee index, and reduced the IRI and IRS responses to arginine load in MSG-treated rats. However, in control animals, vagotomy had no influences on the above two parameters. Though atropine (0.3 mg/rat/30 min) resulted in decrease of plasma IRI in both MSG-treated and control rats, the magnitude in MSG-treated rats was greater than in controls. However, it had no influence on plasma IRS in the two groups. Methoxamine (0.4 mg/rat/30 min) elicited a marked decrease of plasma IRI and IRS in MSG-treated rats, but no significant difference in control rats. On the contrary, a highly significant increase in both plasma IRI and IRS resulted from isoproterenol (4 μg/rat/30 min) not only in MSG-treated rats but also in control rats. (MSG-treated rats, however, showed a marked elevation in plasma IRI and IRS when compared with a respective elevation in control rats.) These findings indicate that hyperinsulinemia is a primary factor in the development of obesity induced by MSG in the rat, and that alterlations of the autonomic nervous system play a significant role in the elevation of plasma insulin. They also reveal that· the increase of somatostatin may be mediated by alterlations of the autonomic nervous system. MSG-treated obese rat can be provide a easily available and valuable animal model for study of hypothalamic-pancreatic axis and hypothalamic obesity.

著者

広瀬良和
神戸大学医学部内科学第二講座

視床下部性肥満ラットの膵内分泌機能と自律神経系の役割に関する研究

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