Brelje T C, Parsons J A, Sorenson R L
University of Minnesota Medical School, Department of Cell Biology and Neuroanatomy, Minneapolis 55455.
Diabetes. 1994 Feb;43(2):263-73. doi: 10.2337/diab.43.2.263.
This study examined the effects of prolactin on beta-cell proliferation in pancreatic islet of Langerhans. Insulin secretion and beta-cell proliferation were significantly increased from neonatal rat islets cultured for 4 days in the presence of either 500 ng/ml ovine prolactin (oPRL) or rat prolactin (rPRL). These effects could be prevented by including anti-oPRL serum in the culture media. Although insulin secretion and beta-cell proliferation were slightly higher during the first 24 h of exposure to rPRL, maximal response was observed after 4 days for insulin secretion and 6-10 days for beta-cell proliferation. The initial mitogenic response of beta-cell to rPRL occurred by the limited recruitment of nondividing beta-cells into the cell cycle and by most daughter cells proceeding directly into additional cell division cycles. Subsequently, the maximal effect of rPRL on beta-cell proliferation was maintained by a higher rate of recruitment of previously nondividing beta-cells into cell cycle with only one fourth of the daughter cells continuing to divide. These observations are difficult to reconcile with the proposal that a limited pool of beta-cells capable of undergoing cell division exists in islets. Instead, these observations suggest that individual beta-cells are transiently re-entering the cell cycle and dividing infrequently in response to rPRL. In this case, the majority of the beta-cells would not be expected to be in an irreversible Go phase. We also demonstrated that the effects of rPRL on beta-cell proliferation occur at normal serum glucose concentrations and are affected by inhibitors of polyamine metabolism. Additional studies on the effects of rPRL on beta-cells should provide important information on the regulation of beta-cell proliferation during conditions of increased insulin demand.
本研究检测了催乳素对胰岛β细胞增殖的影响。在含有500 ng/ml绵羊催乳素（oPRL）或大鼠催乳素（rPRL）的条件下培养4天的新生大鼠胰岛，其胰岛素分泌和β细胞增殖显著增加。在培养基中加入抗oPRL血清可阻止这些效应。尽管在暴露于rPRL的最初24小时内胰岛素分泌和β细胞增殖略有升高，但胰岛素分泌在4天后达到最大反应，β细胞增殖在6 - 10天后达到最大反应。β细胞对rPRL的初始促有丝分裂反应是通过将非分裂β细胞有限地募集到细胞周期中，并且大多数子细胞直接进入额外的细胞分裂周期而发生的。随后，rPRL对β细胞增殖的最大效应通过将先前非分裂的β细胞以更高的速率募集到细胞周期中得以维持，只有四分之一的子细胞继续分裂。这些观察结果难以与胰岛中存在有限数量能够进行细胞分裂的β细胞这一观点相协调。相反，这些观察结果表明，单个β细胞会短暂地重新进入细胞周期，并对rPRL做出不频繁的分裂反应。在这种情况下，大多数β细胞预计不会处于不可逆的G0期。我们还证明，rPRL对β细胞增殖的影响在正常血清葡萄糖浓度下发生，并且受多胺代谢抑制剂的影响。关于rPRL对β细胞影响的进一步研究应能提供有关胰岛素需求增加情况下β细胞增殖调节的重要信息。
