Transcription of the Amylin Gene in Newborn Dogs

Bing-cheng Feng, Jixuan Li, Robert M. Kliegman
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Abstract

To understand the role of amylin, the novel pancreatic hormone, in fuel metabolism of neonatal mammals, the transcription of the amylin gene in newborn dogs was studied under different conditions, such as fasting, hyperinsulinemia, and hyper IGF-1. Our results showed (1) The amylin mRNA level decreased during a 24-h fasting period after birth, 59.1 ± 4.5% at 4 h, 80.1 ± 7.9% at 10 h, and 44.5 ± 3.0% at 24 h, compared to 0-h-fasted controls, respectively. In this period, the decreased mRNA level of the amylin gene and the increased mRNA levels of the gluconeogenic genes showed an inverse ratio relationship. (2) Euglycemic hyperinsulinemic clamp did not alter the amylin mRNA level, 39.6 ± 1.2% (hyperinsulinemia) vs 41.4 ± 3.1% (controls), in newborn dogs, but lowered the amylin mRNA by 35.3%, 64.7 ± 12.5% vs 100.0 ± 12.0%, in adult dogs. (3) Euglycemic hyper-IGF-1 clamp had no effect on the amylin mRNA levels of either newborn or adult dogs, 52.4 ± 9.1% (hyper IGF-1) vs 47.9 ± 4.3% (controls) in newborns and 95.2 ± 12.6% (hyper IGF-1) vs 100.0 ± 14.0% (controls) in adults. The data from the present study showed that amylin may be involved in carbohydrate homeostasis, but may not be able to stimulate gluconeogenesis in newborn dogs during a 24-h fasting period after birth. Whether amylin action may be another mechanism for neonatal hyperglycemia by inducing insulin resistance in peripheral tissues needs further investigation.

新生犬胰淀素基因的转录
为了了解新型胰腺激素amylin在新生哺乳动物燃料代谢中的作用,研究了新生狗在不同条件下(如禁食、高胰岛素血症和高IGF-1)的amylin基因转录。结果显示:(1)出生后禁食24 h时,胰淀粉酶mRNA水平下降,与禁食0 h的对照组相比,禁食4 h时下降59.1±4.5%,禁食10 h时下降80.1±7.9%,禁食24 h时下降44.5±3.0%。这一时期胰淀素基因mRNA水平的降低与糖异生基因mRNA水平的升高呈反比关系。(2)正糖高胰岛素钳夹未改变新生犬胰淀粉酶mRNA水平,分别为高胰岛素血症组(39.6±1.2%)和对照组(41.4±3.1%),但使成年犬胰淀粉酶mRNA水平降低35.3%,分别为64.7±12.5%和100.0±12.0%。(3)正常血糖水平的高IGF-1钳夹对新生儿和成年狗的胰淀粉酶mRNA水平均无影响,新生儿为52.4±9.1%(高IGF-1)对47.9±4.3%(对照组),成年狗为95.2±12.6%(高IGF-1)对100.0±14.0%(对照组)。本研究的数据表明,在出生后24小时禁食期间,胰淀素可能参与碳水化合物稳态,但可能无法刺激新生狗的糖异生。胰淀素是否通过诱导外周组织胰岛素抵抗而成为新生儿高血糖的另一机制还有待进一步研究。
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