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肢端肥大症中的葡萄糖与脂肪代谢:从小鼠模型到患者护理

Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care.

作者信息

Dal Jakob, List Edward O, Jørgensen Jens Otto L, Berryman Darlene E

机构信息

Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.

出版信息

Neuroendocrinology. 2016;103(1):96-105. doi: 10.1159/000430819. Epub 2015 Apr 29.

Abstract

Patients with active acromegaly are frequently insulin resistant, glucose intolerant, and at risk for developing overt type 2 diabetes. At the same time, these patients have a relatively lean phenotype associated with mobilization and oxidation of free fatty acids. These features are reversed by curative surgical removal of the growth hormone (GH)-producing adenoma. Mouse models of acromegaly share many of these characteristics, including a lean phenotype and proneness to type 2 diabetes. There are, however, also species differences with respect to oxidation rates of glucose and fat as well as the specific mechanisms underlying GH-induced insulin resistance. The impact of acromegaly treatment on insulin sensitivity and glucose tolerance depends on the treatment modality (e.g. somatostatin analogs also suppress insulin secretion, whereas the GH antagonist restores insulin sensitivity). The interplay between animal research and clinical studies has proven useful in the field of acromegaly and should be continued in order to understand the metabolic actions of GH.

摘要

患有活动性肢端肥大症的患者常常存在胰岛素抵抗、葡萄糖不耐受,并有发展为显性2型糖尿病的风险。与此同时,这些患者具有相对消瘦的表型,与游离脂肪酸的动员和氧化有关。通过手术治愈性切除产生生长激素(GH)的腺瘤可逆转这些特征。肢端肥大症的小鼠模型具有许多这些特征,包括消瘦的表型和易患2型糖尿病。然而,在葡萄糖和脂肪的氧化速率以及GH诱导的胰岛素抵抗的具体机制方面也存在物种差异。肢端肥大症治疗对胰岛素敏感性和葡萄糖耐量的影响取决于治疗方式(例如,生长抑素类似物也会抑制胰岛素分泌,而GH拮抗剂可恢复胰岛素敏感性)。动物研究和临床研究之间的相互作用已被证明在肢端肥大症领域是有用的,应该继续下去,以便了解GH的代谢作用。

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