Prolactin (<i>in Vitro</i>) Decreases the Glucose Stimulation Threshold, Enhances Insulin Secretion, and Increases Dye Coupling among Islet B Cells*

Sorenson, Robert L.; Brelje, T. Clark; Hegre, Orion D.; Marshall, Sue; Anaya, Pat; Sheridan, Judson D.

doi:10.1210/endo-121-4-1447

Cited by 79 publications

(43 citation statements)

References 18 publications

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“…Similarly, in pregnancy, there is a 50% increase in ␤-cell mass, with larger islets, increased ␤-cell replication, and hypertrophy of ␤-cells (28)(29)(30). Additional functional compensation is seen as changes of threshold for glucose-induced insulin secretion (31). During lactation, the ␤-cell mass returns to nonpregnant levels; this involution results from decreased replication, reduced cell volume from a hypertrophied state to a transient slightly atrophied one, and increased apoptosis (30,32,33).…”

Section: Dynamics Of ␤-Cell Massmentioning

confidence: 99%

beta-cell turnover: its assessment and implications.

2001

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The pancreatic ␤-cells are responsible for the maintenance of the body's glucose levels within a very narrow range; their population is dynamic and undergoes compensatory changes to maintain euglycemia. The structural parameters that allow mass changes (replication, neogenesis, cell volume changes, and cell death) can now be assessed and have proved to be powerful tools. Changes in one parameter can dramatically affect the ␤-cell mass. Unfortunately, conclusions are often drawn on measurements that do not assess ␤-cell mass but only relative volumes. Throughout the lifetime of a mammal, low levels of ␤-cell replication and apoptosis are balanced and result in a slowly increasing mass. The balance allows gradual replacement of the ␤-cell population; thus, ␤-cells should be considered a slowly renewed tissue. Two major implications of ␤-cell turnover are that 1) at any time, the ␤-cells would be at different ages and 2) any limitation on replacement could have dire consequences for glucose homeostasis. Diabetes 50 (Suppl. 1):S20-S24, 2001 T he evidence that the ␤-cell mass exists in a dynamic state is becoming increasingly strong. Accumulated experimental data from rodents show that ␤-cells change in mass and function to maintain plasma glucose levels in a very narrow range. The structural parameters that allow mass changes (replication, neogenesis, cell volume changes, and cell death) have been recognized for many years, but only in the last decade have integrated analyses of these parameters been done. From these studies, several concepts have emerged:• There is growth of the ␤-cell mass throughout the life span.• There is continued renewal and loss, that is, turnover, of ␤-cells.• There exist additional compensatory changes to maintain glucose homeostasis. This perspective will address the basis of these concepts, address the assessment of the components that regulate ␤-cell mass and turnover, and discuss the implications of having a slowly renewed and ever-expanding ␤-cell mass. ASSESSMENT TOOLS FOR ␤-CELL TURNOVERTo be able to document ␤-cell turnover, there are a number of parameters one must quantitate: ␤-cell mass, ␤-cell number, and ␤-cell replication. Two other parameters, ␤-cell neogenesis and ␤-cell apoptosis, can be documented for frequency, but rates for these cannot as yet be measured.The assessment of ␤-cell mass has proved to be a powerful tool. Unfortunately, often conclusions have been drawn on measurements that do not assess ␤-cell mass but only relative volumes. To estimate ␤-cell mass, one must have the pancreatic weight as well as quantitate the relative volume (also called relative density, volume density, or percentage of pancreatic tissue) of the ␤-cells. The pancreatic weight can be equated with pancreatic volume or mass if one makes the reasonable assumption that 1 cm 3 tissue weighs 1 g. With data for relative volume and pancreatic weight, one can estimate the absolute weight or mass of the ␤-cells (Fig. 1). Many different methods for quantitating the relative volume of a tissue exi...

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Section: Dynamics Of ␤-Cell Massmentioning

confidence: 99%

beta-cell turnover: its assessment and implications.

2001

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“…One of the target tissues of PRL is the endocrine pancreas where PRL and the related hormones growth hormone (GH) and placental lactogen have been found to be potent growth factors for the pancreatic ␤-cell and to enhance insulin production and glucose sensitivity of these cells (2)(3)(4)(5)(6). The stimulatory effects of PRL, GH, and placental lactogen are thought to play an important role in the adaptive growth and function of the ␤-cells during conditions of increased insulin demands.…”

Section: Prolactin (Prl)mentioning

confidence: 99%

Regulation of Prolactin Receptor (PRLR) Gene Expression in Insulin-producing Cells

Galsgaard¹,

Nielsen²,

Møldrup³

1999

Journal of Biological Chemistry

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Expression of the prolactin receptor (PRLR) gene is increased in pancreatic islets during pregnancy and in vitro in insulin-producing cells by growth hormone (GH) and prolactin (PRL). The 5-region of the rat PRLR gene contains at least three alternative first exons that are expressed tissue-specifically because of differential promoter usage. We show by reverse transcription-polymerase chain reaction analysis that both exon 1A-and exon 1C-containing PRLR transcripts are expressed in rat islets and that human (h)GH, ovine (o)PRL, and bovine (b)GH increase exon 1A expression 6.5 ؎ 0.8-fold, 6.8 ؎ 0.7-fold, and 3.9 ؎ 0.7-fold and exon 1C expression 4.8 ؎ 0.4-fold, 4.4 ؎ 0.6-fold, and 2.5 ؎ 0.7-fold, respectively. Expression of exon 1B was not detectable. The transcriptional activities of reporter constructs containing the 1A, 1B, or 1C promoter were found to be 22.8-fold, 2.7-fold, and 8.0-fold, respectively, above that of a promoterless reporter construct when transfected into the insulin-producing INS-1 cells. The transcriptional activity of the 1A promoter construct was increased 8.9 ؎ 1.9-fold by 0.5 g/ml hGH. Responsiveness to hGH of the 1A promoter was localized to the region from ؊225 to ؉81 with respect to the transcription start site. This region contains the sequence TTCTAGGAA that by gel retardation experiments was shown to bind the transcription factors STAT5a and STAT5b in response to stimulation by hGH, oPRL, or bGH. Mutation of this ␥-activated sequence-like element completely abolished transcriptional induction of the 1A promoter by hGH. Our results suggest that GH and PRL increase the levels of exon 1A-and 1C-containing PRLR mRNA species and furthermore that the transcriptional activity of the 1A promoter is increased via activation of STAT5a and STAT5b.

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1994

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Neonatal rat islets exhibit a reduced secretory response to glucose, compared to adult rat islets. The maturation of the secretory response is stimulated by prolactin (PRL). We show here by immunoblot analysis that PRL increases the B-cell/liver glucose transporter GLUT2 in membrane fractions from cultured neonatal rat islets. This increase (+86%) may explain, at least in part, the development of a mature glucose response. G proteins modulate insulin secretion from pancreatic p-cells. We show here by immunoblot analysis that, in contrast to the effect on GLUTZ, PRL treatment does not modify the G protein subunits ai2, ai3, cco, as, ccq and 835 and 836, in cultured neonatal islets.

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Prolactin (in Vitro) Decreases the Glucose Stimulation Threshold, Enhances Insulin Secretion, and Increases Dye Coupling among Islet B Cells*

Cited by 79 publications

References 18 publications

beta-cell turnover: its assessment and implications.

beta-cell turnover: its assessment and implications.

Regulation of Prolactin Receptor (PRLR) Gene Expression in Insulin-producing Cells

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

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