The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest.
The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest.
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作者：
Alibegovic AC;Sonne MP;Højbjerre L;Hansen T;Pedersen O;van Hall G;Holst JJ;Stallknecht B;Dela F;Vaag A
本研究的目的是确定2型糖尿病相关的转录因子7样2（TCF 7 L2）rs7903146的T等位基因是否与胰岛素分泌受损相关，以补偿卧床休息引起的胰岛素抵抗。总共有38名健康的年轻白人男性进行了研究之前和之后的卧床休息，使用高胰岛素-正葡萄糖钳夹技术结合间接量热法之前，静脉内葡萄糖耐量试验。使用ABI 7900系统进行等位基因区分，对TCF 7 L2 rs7903146进行基因分型。遗传分析是假设显性遗传模式进行的。在卧床休息前，T等位基因携带者的第一时相胰岛素反应（FPIR）显著低于CC基因型携带者，有和没有校正胰岛素抵抗。卧床引起的胰岛素抵抗引起的FPIR升高在T等位基因携带者中较低（P < 0.001）。卧床休息前后，T等位基因携带者的空腹血浆胰高血糖素水平显著降低。虽然CC基因型携带者的肝脏胰岛素抵抗增加，但TCF 7 L2 rs7903146并不影响外周胰岛素作用或卧床休息前后的脂解速率。TCF 7 L2 rs7903146的T等位基因的健康携带者表现出响应于静脉内葡萄糖的胰岛素分泌增加减少，以补偿由卧床休息诱导的胰岛素抵抗。减少旁分泌胰高血糖素刺激可能导致TCF 7 L2 rs7903146 T等位基因携带者β细胞功能受损，与2型糖尿病风险增加相关。
The aim of this study was to determine whether the type 2 diabetes–associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest. A total of 38 healthy young Caucasian men were studied before and after bed rest using the hyperinsulinemic-euglycemic clamp technique combined with indirect calorimetry preceded by an intravenous glucose tolerance test. The TCF7L2 rs7903146 was genotyped using allelic discrimination performed with an ABI 7900 system. The genetic analyses were done assuming a dominant model of inheritance. The first-phase insulin response (FPIR) was significantly lower in carriers of the T-allele compared with carriers of the CC genotype before bed rest, with and without correction for insulin resistance. The incremental rise of FPIR in response to insulin resistance induced by bed rest was lower in carriers of the T-allele (P < 0.001). Fasting plasma glucagon levels were significantly lower in carriers of the T-allele before and after bed rest. While carriers of the CC genotype developed increased hepatic insulin resistance, the TCF7L2 rs7903146 did not influence peripheral insulin action or the rate of lipolysis before or after bed rest. Healthy carriers of the T-allele of TCF7L2 rs7903146 exhibit a diminished increase of insulin secretion in response to intravenous glucose to compensate for insulin resistance as induced by bed rest. Reduced paracrine glucagon stimulation may contribute to the impairment of β-cell function in the carriers TCF7L2 rs7903146 T-allele associated with increased risk of type 2 diabetes.
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影响因子：
8.2
作者：
Pilgaard, K.;Jensen, C. B.;Vaag, A. A.
通讯作者：
Vaag, A. A.
影响因子：
7.7
作者：
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通讯作者：
Froguel, Philippe
影响因子：
7.7
作者：
Plomgaard, P;Bouzakri, K;Pedersen, BK
通讯作者：
Pedersen, BK
影响因子：
158.5
作者：
Florez, Jose C.;Jablonski, Kathleen A.;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
7.7
作者：
Alibegovic AC;Højbjerre L;Sonne MP;van Hall G;Stallknecht B;Dela F;Vaag A
通讯作者：
Vaag A