Effect of Prolactin Versus Growth Hormone on Islet Function and the Importance of Using Homologous Mammosomatotropic Hormones*

Abstract

The purpose of this study was to determine the effects of homologous rat PRL (rPRL) and rat GH (rGH) on islet B-cell function in neonatal and adult rat islets in vitro. In neonatal rat islets, exposure to rPRL for more than 24 h was necessary for a stimulatory effect on insulin secretion. By day 4, insulin secretion was 3.8-fold greater in the islets cultured with rPRL. rGH had a modest effect on insulin secretion, and this effect was additive with that of rPRL. Both rPRL and rGH increased islet insulin content and [3H]thymidine incorporation. After removal of rPRL, more than 24 h were necessary to detect a reversal in the level of insulin secretion. In addition, even after 5 days without rPRL the previously treated islets still had elevated levels of insulin secretion. In a dose-response study of rPRL on insulin secretion, a detectable effect was observed at 62.5 ng/ml, with a half-maximal effect of approximately 100 ng/ml. Glucose oxidation by neonatal islets was enhanced by rPRL treatment, but not by rGH treatment. In adult rat islets, exposure to rPRL, but not to rGH, enhanced insulin secretion. In contrast, when using heterologous human GH, results similar to those obtained with rPRL, but not rGH, were observed. The results from these experiments indicate that rPRL and rGH have both individual and shared regulatory effects on rat islets. However, it is rPRL and not rGH that has the primary influence on insulin secretion. When interpreting studies examining the effect of GH and PRL on islet function, it is important to consider whether homologous hormones are used.

Adaptation of pancreatic islet B-cells during the last third of pregnancy: regulation of B-cell function and proliferation by lactogenic hormones in rats

“…Therefore, most B-cells in the last third of pregnancy may no longer proliferate in response to lactogenic hormones. Several in vivo and in vitro studies have shown that prolonged stimulation of islets by lactogenic hormones can maintain the enhanced islet functions for extended periods (3,4,21). These results suggest the possibility that a downregulation mechanism may exist on the function of islet B-cells in the last third of pregnancy.…”

GH Signalling in Pancreatic β-Cells

“…Table 2 summarizes the reported actions of GH-related hormones in various types of insulin-secreting cells. In addition to their mitogenic effect [4][5][6][7][8][9][10][11], these hormones are known to stimulate insulin biosynthesis [6,9,[12][13][14], to promote oxidative metabolism of glucose [7,9], and to increase GLUT2 expression [15], thereby contributing to the functional maturation (increase in sensitivity to glucose for the stimulation of insulin secretion) of /3-cells [14][15][16]. In view of these various effects of GH-related peptides in /3-cells, to study their mode of action might reveal crucial mechanisms for the regulation of growth and the function of these cells, which are only partially understood [2,17].…”

Prolactin treatment increases GLUT2 but not the G protein subunit content in cell membranes from cultured neonatal rat islets

“…Among these hormones, prolactin (PRL) plays an important role in the maturation of the glucose sensing mechanisms. In fact, PRL treatment affects several physiological parameters of pancreatic B-cell, such as the glucose-induced reduction of K+ permeability [4], the glucose stimulation threshold [5], cell-to-cell coupling [5], [3H]thymidine incorporation [6] and the proliferation of j&cells in vitro [7]. GLUT2, the liver/j?cell glucose transporter, plays a key role in the glucose sensing apparatus [8].…”