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T C Brelje

Publications and source records attributed to T C Brelje.

22 records · Page 2Linked to original sources

Effect of prolactin versus growth hormone on islet function and the importance of using homologous mammosomatotropic hormones.

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.

Animals↗

Three-dimensional imaging of intact isolated islets of Langerhans with confocal microscopy.

We present a new technique for analyzing the three-dimensional structure of intact isolated islets of Langerhans. Adult rat and human islets were stained with whole-mount immunofluorescence techniques and optically sectioned with a confocal microscope. This has several advantages over traditional methods: 1) the technical difficulties in serial sectioning and handling the large numbers of sections are avoided, 2) optical sectioning by confocal microscopy gives improved resolution and strongly suppresses light from out-of-focus structures, and 3) entire islets can be rapidly imaged for the presence of positive staining. This new technique should facilitate the study of the three-dimensional structure of islets of Langerhans.

Animals↗

Nutrient and hormonal regulation of the threshold of glucose-stimulated insulin secretion in isolated rat pancreases.

This study demonstrates that the threshold of glucose-stimulated insulin secretion can be regulated in vivo by long term hormonal and nutrient modifications. The sensitivity of the pancreatic B-cell to glucose stimulation was determined by examining the pattern of insulin release from pancreases perfused with linear glucose gradients. Male rats infused with ovine PRL for 4 days and rats receiving five hourly injections of glucose had a lower threshold and enhanced rates of insulin release at all stimulatory glucose concentrations. Infusion of bGH for 4 days was without effect on glucose gradient-stimulated insulin release. Fasting the rats for 48 h resulted in an elevation of the threshold and a substantial reduction in the extent of insulin release. To determine possible processes involved in these long term modifications of the threshold of glucose-stimulated insulin secretion, the in vitro effect of potentiators of insulin release was examined. Forskolin, glucagon, cholecystokinin, and carbamylcholine were able to lower the threshold and increase the extent of insulin release. This suggests that the long term regulation of insulin secretion may modulate processes controlling cAMP concentrations and the hydrolysis of phosphoinositides in pancreatic B-cells. Also, the proposed incretin gastric inhibitory polypeptide was capable of lowering the threshold and increasing insulin secretion at stimulatory glucose concentrations. The consequences of a decreased threshold is a markedly enhanced insulin secretion at normal serum glucose concentrations.

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Prolactin (in vitro) decreases the glucose stimulation threshold, enhances insulin secretion, and increases dye coupling among islet B cells.

The purpose of this study was to determine the in vitro effect of ovine PRL (oPRL) on the dynamics of insulin secretion and dye coupling among islet B cells. The effect of oPRL (2 micrograms/ml) on insulin secretion was time dependent and reached a maximum on day 4 when there was a 2.4-fold increase in insulin secretion from cultured neonatal rat islets (n = 6, P less than 0.001). When islets cultured in the presence of oPRL for 4 days were perifused, 300 mg/dl glucose stimulation resulted in insulin release of 131 +/- 20 microU/ml.100 micrograms islet tissue as compared to control islets 94 +/- 20 microU/ml.100 micrograms islet tissue (n = 7, P less than 0.02). Stimulation of the islets with a linear 30-250 mg/dl glucose gradient resulted in a threshold for glucose-stimulated insulin secretion of 73 +/- 6 mg/dl glucose for the oPRL treated islets (n = 7) as compared to a threshold of 123 +/- 6 mg/dl glucose for control islets (n = 7, P less than 0.001). Mean islet volume was unchanged after 4 days of oPRL treatment but was 34% greater after 8 days (n = 6, P less than 0.001). Dye coupling among central islet B cells was also increased after in vitro treatment with oPRL for 4 days. The mean projected area of dye spread was 2-fold greater in the oPRL treated islets (n = 33) in comparison to the control islets (n = 33, P less than 0.05). These results indicate that in vitro lactogen treatment, in the form of oPRL, alters insulin secretory behavior and B cell junctional communication and supports our hypothesis that lactogen, insulin secretion, and junctional communication among B cells are related.

Animals↗