Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy.

Abstract

Up-regulation of maternal islet function is essential to accommodate the increased demand for insulin during pregnancy. Previously, we suggested that lactogenic activity regulates islet function during pregnancy. However, this hypothesis was based on the effect of homologous PRLs on islets, since the homologous placental lactogens (or islets) were unavailable. In this study we examine the direct effects of homologous placental lactogens (PL), PRL, and GH on insulin secretion and B-cell division in rat, mouse, and human islets in vitro. Neonatal rat islets were cultured for 8 days in the presence of 0-1000 ng/ml rat PL-I (rPL-I), rPRL, or rGH. Media were changed daily, and the insulin concentration was determined. rPL-I and rPRL (500 ng/ml) treatment resulted in a 2-fold increase in insulin secretion. rGH (1000 ng/ml) elicited a 30% increase in insulin secretion. Similarly, cell replication, as indicated by BrdU incorporation into B-cells, was increased 4-fold in the presence of rPL-I and rPRL. The ED50 for insulin secretion and 5'-bromo-2'-deoxyuridine (BrdU) incorporation was 70 ng/ml for rPL-I and 150 ng/ml for rPRL. Similarly, in adult rat islets, insulin secretion was increased 1.6-fold, and B-cell replication increased 3-fold in the presence of the lactogenic hormones. Neonatal mouse islets were cultured for 8 days in the presence of 500 ng/ml mouse (m) PL-I, mPL-II, mPRL, or mGH. mPL-I, mPL-II, and mPRL treatment resulted in a 2-fold increase in insulin secretion. mGH elicited a 30% increase in insulin secretion. BrdU incorporation into B-cells was increased 3-fold in the presence of mPL-I and mPRL and 2-fold in the presence of mPL-II. Adult human islets were cultured for 8 days in the presence of 1 microgram/ml human (h) PL, hPRL, or hGH. For human islets isolated from six pancreata obtained from females, hPL (138 +/- 10%), hPRL (133 +/- 9%), and hGH (117 +/- 3%) significantly increased insulin secretion compared to that from control islets. This study compares the direct effects among homologous PLs, PRLs, and GHs on insulin secretion and B-cell division in rat, mouse, and human islets. The results indicate that placental lactogen directly regulates islet function in several species and is probably the principal hormone responsible for the increased islet function observed during normal pregnancy.

Physiology of Reproduction

“…The placental lactogens contribute to the development of the mammary glands and to stimulation of progesterone synthesis in the corpora lutea during pregnancy. Recent studies have demonstrated that placental lactogens stimulate insulin secretion and the proliferation of maternal B cells in the pancreatic islets during the latter half of pregnancy in the rat (Brelje et al, 1993;Kawai and Kishi, 1997).…”

Co‐ordinated regulation of neurogenin‐3 expression in the maternal and fetal pancreas during pregnancy

“…Studies of pancreatic tissue from pregnant women have shown that the most likely source of the increased beta cell mass during pregnancy is neogenesis from unknown progenitor cells as no proliferation of beta cells was seen, whereas the number of small islets was increased . In rodents, it has been shown that somatolactogenic hormones such as prolactin, placental lactogen and placental growth hormone have an important role in the increase in beta cell mass because they are able to stimulate proliferation of beta cells in vitro . A twofold increase in insulin secretion and a fourfold increase in incorporation of 5‐bromo‐2′‐deoxyuridine, an indicator of DNA synthesis during S‐phase, were seen after treatment with rat placental lactogen‐1 and rat prolactin.…”

Prolactin and oleic acid synergistically stimulate β-cell proliferation and growth in rat islets

“…Islet cell proliferation was assessed by examining BrdU incorporation as described previously 4 , 14 , 20 , 21 . 10 µM BrdU was added during the last 12 hr of culture.…”

“…Glass beads were included in the mounting media (Prolong Gold anti-fade reagent; Life Technologies, Grand Island, NY) to support the coverslips and prevent excessive deformation of the islets. As described previously, 4 , 14 , 20 , 21 the number of BrdU-labeled nuclei/islet was determined by direct observation using a conventional fluorescence microscope. The scattered BrdU-labeled nuclei (typically, 0 to 50) are counted while focusing through intact islets.…”