Decreased glucose stimulation threshold, enhanced insulin secretion, and increased beta cell coupling in islets of prolactin-treated rats

Abstract

In order to determine the effect of lactogen on insulin secretion and junctional coupling among islet beta cells, ovine prolactin (oPRL) was infused by Alzet minipumps into female rats for 4 days. This treatment produced an oPRL level of 994 +/- 122 ng/ml which, combined with residual rat PRL (rPRL) (12 +/- 2 ng/ml), represented nearly a 20-fold increase from control (rPRL: 53 +/- 17 ng/ml). In addition, plasma insulin was increased nearly 50% (control: 21.9 +/- 3 microU/ml; experimental: 30.3 +/- 3 microU/ml; p less than 0.05). When pancreata from lactogen-treated and control animals were perfused with linear 30-200 mg/dl glucose gradients, the apparent glucose threshold for insulin secretion in the experimental group was nearly 33% lower than that of the controls (i.e., 70 +/- 4.6 mg/dl vs. 104 +/- 7.5 mg/dl; p less than 0.01). The oPRL treatment also increased dye coupling among beta cells. Central cells in islets isolated from lactogen-treated and control animals were injected with Lucifer Yellow CH to estimate the extent of gap junctional coupling. There was nearly a twofold increase in the projected area of dye transfer per injection in the experimental vs. the controls: 4,607 +/- 575 micron 2 vs. 2,302 +/- 474 micron 2, respectively; p less than 0.02. The effects of oPRL decreased the apparent glucose threshold for insulin release, increased the above-threshold glucose-induced insulin secretion, and increased the extent of dye coupling among beta cells. These changes in insulin secretion and dye coupling closely resemble those observed in islets from pregnant rats.