GLUCAGON STIMULATION OF BROWN ADIPOSE-TISSUE GROWTH AND THERMOGENESIS

GLUCAGON STIMULATION OF BROWN ADIPOSE-TISSUE GROWTH AND THERMOGENESIS
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DOI:
10.1152/ajpregu.1987.252.1.r160
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发表时间:
1987-01-01
影响因子:
--
通讯作者:
MORLEY, JE
MORLEY, JE
中科院分区:
其他
文献类型:
--
作者:
BILLINGTON, CJ;BARTNESS, TJ;MORLEY, JE

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尽管长期观察到胰高血糖素的全身产热作用,但胰高血糖素在激活棕色脂肪组织产热中的作用并不常被研究。我们研究了给予胰高血糖素对棕色脂肪组织产生改变的能力,这种改变与接受的棕色脂肪活性刺激(寒冷、去甲肾上腺素和过度喂养)产生的改变相似。与注射生理盐水的对照组相比,对雄性Sprague-Dawley大鼠注射胰高血糖素(1 mg/kg)18天后,饲料效率降低,棕色脂肪组织重量、蛋白质含量、DNA含量和线粒体质量增加,这反映在细胞色素氧化酶活性上。所观察到的变化与阳性对照组给予去甲肾上腺素(250 μ g/kg)诱导的这些相同参数的变化相似,但幅度较小。胰高血糖素给药(1 mg/kg)4天后,细胞色素氧化酶和脂蛋白脂肪酶的比活性增加。胰高血糖素给药8天后,出现了与给药18天相似的全垫活性变化。胰高血糖素也增加了4天和8天后的全垫脂蛋白脂酶活性。手术失神经支配的肩胛间棕色脂肪组织保留了其对外源性胰高血糖素的反应能力,尽管反应的幅度减小。在胰高血糖素(lmg/kg)5天后,测量鸟苷5 '-二磷酸(GDP)与棕色脂肪组织线粒体的结合作为功能状态的评估。无论以皮摩尔/毫克线粒体蛋白还是纳摩尔/垫表示,GDP结合相对于对照都有增加。(250字处删节)
Despite long-standing observations of a whole-body thermogenic effect of glucagon, the role of glucagon in activating thermogenesis in brown adipose tissue has not often been studied. We investigated the ability of administered glucagon to produce alterations in brown adipose tissue similar to changes produced by accepted stimuli of brown fat activity: cold, norepinephrine, and overfeeding. Eighteen days of glucagon injections (1 mg/kg) to male Sprague-Dawley rats produced, relative to saline-injected controls, decreases in feed efficiency and increases in brown adipose tissue weight, protein content, DNA content, and mitochondrial mass as reflected in cytochrome oxidase activity. The observed changes were similar, though of lesser magnitude, to changes produced in these same parameters induced by administration of norepinephrine (250 micrograms/kg) for a positive control group. Four days of glucagon administration (1 mg/kg) produced increases in specific activity of cytochrome oxidase and lipoprotein lipase. After 8 days of glucagon administration, changes in whole-pad activity similar to those seen with 18 days of administration were present. Glucagon also increased whole-pad lipoprotein lipase activity after 4 and 8 days. Surgically denervated interscapular brown adipose tissue retained its ability to respond to exogenous glucagon, though the magnitude of the response was diminished. Guanosine 5'-diphosphate (GDP) binding to brown adipose tissue mitochondria was measured as an assessment of functional state after 5 days of glucagon (1 mg/kg). There was an increase in GDP binding relative to controls whether expressed as picomoles per milligram mitochondrial protein or nanomoles per pad.(ABSTRACT TRUNCATED AT 250 WORDS)