Nielsen J H, Linde S, Welinder B S, Billestrup N, Madsen O D
Hagedorn Research Laboratory, Gentofte, Denmark.
Mol Endocrinol. 1989 Jan;3(1):165-73. doi: 10.1210/mend-3-1-165.
The regulation of the growth of the pancreatic beta-cell is poorly understood. There are previous indications of a role of GH in the growth and insulin production of the pancreatic islets. In the present study we present evidence for a direct long-term effect of GH on proliferation and insulin biosynthesis of pancreatic beta-cells in monolayer culture. In culture medium RPMI 1640 supplemented with 2% normal human serum islets or dissociated islet cells from newborn rats maintained their insulin-producing capacity. When supplemented with 1-1000 ng/ml pituitary or recombinant human GH the islet cells attached, spread out, and proliferated into monolayers mainly consisting of insulin-containing cells. The number of beta-cells in S-phase was increased from 0.9-6.5% as determined by immunochemical staining of bromodeoxyuridine incorporated into insulin-positive cells. The increase in cell number was accompanied with a continuous increase in insulin release to the culture medium reaching a 10- 20-fold increase after 2-3 months with a half-maximal effect at about 10 ng/ml human GH. The biosynthesis of (pro)insulin was markedly increased with a normal rate of conversion of proinsulin to insulin. It is concluded that GH is a potent growth factor for the differentiated pancreatic beta-cell.
胰腺β细胞生长的调控机制目前还知之甚少。先前有迹象表明生长激素（GH）在胰岛的生长和胰岛素产生中发挥作用。在本研究中，我们提供证据表明，GH对单层培养的胰腺β细胞的增殖和胰岛素生物合成具有直接的长期影响。在补充有2%正常人血清的RPMI 1640培养基中，新生大鼠的胰岛或解离的胰岛细胞保持了它们产生胰岛素的能力。当补充1 - 1000 ng/ml的垂体或重组人生长激素时，胰岛细胞附着、铺展并增殖形成主要由含胰岛素细胞组成的单层。通过对掺入胰岛素阳性细胞中的溴脱氧尿苷进行免疫化学染色测定，处于S期的β细胞数量从0.9%增加到6.5%。细胞数量的增加伴随着向培养基中胰岛素释放的持续增加，在2 - 3个月后增加了10 - 20倍，在约10 ng/ml人生长激素时达到半数最大效应。（前）胰岛素的生物合成显著增加，胰岛素原向胰岛素的转化率正常。得出的结论是，GH是分化的胰腺β细胞的一种强大生长因子。
