Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: A model for weight gain with intensive insulin therapy
Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: A model for weight gain with intensive insulin therapy
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DOI：
10.1152/ajpendo.00262.2012
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发表时间：
2013-01-01
影响因子：
5.1
通讯作者：
Sherwin, Robert S.
中科院分区：
文献类型：
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作者：
McNay, Ewan C.;Teske, Jennifer A.;Sherwin, Robert S.
McNay EC，Teske JA，Kotz CM，Dunn-Meynell A，Levin Be，McCrimmon RJ，Sherwin RS。长期、间歇性、胰岛素诱导的低血糖会产生明显的肥胖，而不会出现吞噬过度或胰岛素抵抗：这是一种通过强化胰岛素治疗而导致体重增加的模型。Am J生理学内分泌Metab 304：E131-E138,2013。2012年11月20日首次出版；DOI：10.1152/ajpendo.00262.2012。-胰岛素治疗糖尿病的一个主要副作用是体重增加，这限制了患者的依从性，并可能带来额外的健康风险。尽管导致体重增加的机制尚不清楚，但有人认为这可能与低血糖反复发作的发生率有关。在这里，我们提出了一个啮齿动物模型，在没有糖尿病的情况下，体重显著增加与每周胰岛素诱导的低血糖发作有关。胰岛素治疗导致体重和脂肪质量的显著增加，伴随着运动活动的减少，对寒冷挑战的反应降低了产热能力，并减少了棕色脂肪解偶联蛋白基因的表达。然而，胰岛素治疗对总摄食量没有影响，也没有对下丘脑神经肽Y或前阿片黑素皮质素mRNA的表达产生影响，而且胰岛素治疗的动物没有出现胰岛素抵抗。我们的结果表明，反复的医源性低血糖会导致体重增加，这种体重增加与代谢调节的多方面缺陷有关，而不是与热量摄入量的慢性增加有关。
McNay EC, Teske JA, Kotz CM, Dunn-Meynell A, Levin BE, McCrimmon RJ, Sherwin RS. Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: A model for weight gain with intensive insulin therapy. Am J Physiol Endocrinol Metab 304: E131-E138, 2013. First published November 20, 2012; doi:10.1152/ajpendo.00262.2012.-A major side effect of insulin treatment of diabetes is weight gain, which limits patient compliance and may pose additional health risks. Although the mechanisms responsible for this weight gain are poorly understood, it has been suggested that there may be a link to the incidence of recurrent episodes of hypoglycemia. Here we present a rodent model of marked weight gain associated with weekly insulin-induced hypoglycemic episodes in the absence of diabetes. Insulin treatment caused a significant increase in both body weight and fat mass, accompanied by reduced motor activity, lowered thermogenesis in response to a cold challenge, and reduced brown fat uncoupling protein mRNA. However, there was no effect of insulin treatment on total food intake nor on hypothalamic neuropeptide Y or proopiomelanocortin mRNA expression, and insulin-treated animals did not become insulin-resistant. Our results suggest that repeated iatrogenic hypoglycemia leads to weight gain, and that such weight gain is associated with a multifaceted deficit in metabolic regulation rather than to a chronic increase in caloric intake.