A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.
A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.
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DOI：
10.1210/jcem.82.5.3914
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发表时间：
1997-05
期刊：
影响因子：
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通讯作者：
M. Warren-Perry;S. Manley;D. Ostrega;K. Polonsky;S. Mussett;P. Brown;R. Turner
中科院分区：
文献类型：
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作者：
M. Warren-Perry;S. Manley;D. Ostrega;K. Polonsky;S. Mussett;P. Brown;R. Turner
一名58岁的肥胖白色白人男性2型糖尿病患者，进入英国前瞻性糖尿病研究，发现空腹总胰岛素原水平升高708 pmol/L（-1）（正常范围，3-16 pmol/L（-1）），正常特定血浆胰岛素水平升高29 pmol/L（-1）（正常范围，21-75 pmol/L（-1））。RIA测定的免疫反应性血浆胰岛素为503 pmol/L（-1）。提取DNA，通过PCR扩增胰岛素基因，并通过直接测序，鉴定了一个新的点突变，G1552 C，这导致在位置65的精氨酸（CGT）取代脯氨酸（CCT）。这阻止了胰腺β细胞中的加工蛋白酶对C肽A链二元切割位点（lys-arg）的切割。血浆胰岛素原和胰岛素水平与野生型和突变型等位基因的表达一致，与野生型和突变型等位基因的表达一致。雅阁。G1552 C突变与糖尿病无关，因为它存在于一个37岁的非糖尿病女儿中，而不是一个35岁的患有妊娠糖尿病的女儿。
A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L(-1) (normal range, 3-16 pmol/L(-1)) and normal specific plasma insulin level 29 pmol/L(-1) (normal range, 21-75 pmol/L(-1)). Immunoreactive plasma insulin, measured by RIA, was 503 pmol/L(-1). DNA was extracted, the insulin gene amplified by the PCR, and by direct sequencing, a novel point mutation, G1552C, was identified, which resulted in the substitution of proline (CCT) for arginine (CGT) at position 65. This prevented cleavage of the C-peptide A-chain dibasic cleavage site (lys-arg) by the processing protease in the pancreatic beta-cells. The plasma proinsulin and insulin levels were in accord with expression of both the wild-type and the mutant alleles. The G1552C mutation was not linked with diabetes, because it was present in a 37-yr-old nondiabetic daughter and not in a 35-yr-old daughter who had had gestational diabetes.