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Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2.

Publication ,  Journal Article
Petryk, A; Fleenor, D; Driscoll, P; Freemark, M
Published in: J Endocrinol
March 2000

Previous studies have shown that lactogenic hormones stimulate beta-cell proliferation and insulin production in pancreatic islets. However, all such studies have been conducted in cells incubated in medium containing glucose. Since glucose independently stimulates beta-cell replication and insulin production, it is unclear whether the effects of prolactin (PRL) on insulin gene expression are exerted directly or through the uptake and/or metabolism of glucose. We examined the interactions between glucose and PRL in the regulation of insulin gene transcription and the expression of glucose transporter-2 (glut-2) and glucokinase mRNAs in rat insulinoma (INS-1) cells. In the presence of 5.5 mM glucose, the levels of preproinsulin and glut-2 mRNAs in PRL-treated cells exceeded the levels in control cells (1.7-fold, P<0.05 and 2-fold, P<0.05 respectively). The maximal effects of PRL were noted at 24-48 h of incubation. PRL had no effect on the levels of glucokinase mRNA. The higher levels of glut-2 mRNA were accompanied by an increase in the number of cellular glucose transporters, as demonstrated by a 1. 4- to 2.4-fold increase in the uptake of 2-deoxy-d-[(3)H]glucose in PRL-treated INS-1 cells (P<0.001). These findings suggested that the insulinotropic effect of PRL is mediated, in part, by induction of glucose transport and/or glucose metabolism. Nevertheless, even in the absence of glucose, PRL stimulated increases in the levels of preproinsulin mRNA (3.4-fold higher than controls, P<0.0001) and glut-2 mRNA (2-fold higher than controls, P<0.01). These observations suggested that PRL exerts glucose-independent as well as glucose-dependent effects on insulin gene expression. Support for this hypothesis was provided by studies of insulin gene transcription using INS-1 cells transfected with a plasmid containing the rat insulin 1 promoter linked to a luciferase reporter gene. Glucose and PRL, alone and in combination, stimulated increases in cellular luciferase activity. The relative potencies of glucose (5.5 mM) alone, PRL alone, and glucose plus PRL in combination were 2.2 (P<0.001), 3.4 (P<0.01), and 7.9 (P<0.0001) respectively. Our findings suggest that glucose and PRL act synergistically to induce insulin gene transcription.

Duke Scholars

Published In

J Endocrinol

DOI

ISSN

0022-0795

Publication Date

March 2000

Volume

164

Issue

3

Start / End Page

277 / 286

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats
  • RNA, Messenger
  • Protein Precursors
  • Prolactin
  • Proinsulin
  • Pancreatic Neoplasms
  • Monosaccharide Transport Proteins
  • Luciferases
  • Insulinoma
 

Citation

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Petryk, A., Fleenor, D., Driscoll, P., & Freemark, M. (2000). Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2. J Endocrinol, 164(3), 277–286. https://doi.org/10.1677/joe.0.1640277
Petryk, A., D. Fleenor, P. Driscoll, and M. Freemark. “Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2.J Endocrinol 164, no. 3 (March 2000): 277–86. https://doi.org/10.1677/joe.0.1640277.
Petryk A, Fleenor D, Driscoll P, Freemark M. Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2. J Endocrinol. 2000 Mar;164(3):277–86.
Petryk, A., et al. “Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2.J Endocrinol, vol. 164, no. 3, Mar. 2000, pp. 277–86. Pubmed, doi:10.1677/joe.0.1640277.
Petryk A, Fleenor D, Driscoll P, Freemark M. Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2. J Endocrinol. 2000 Mar;164(3):277–286.
Journal cover image

Published In

J Endocrinol

DOI

ISSN

0022-0795

Publication Date

March 2000

Volume

164

Issue

3

Start / End Page

277 / 286

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats
  • RNA, Messenger
  • Protein Precursors
  • Prolactin
  • Proinsulin
  • Pancreatic Neoplasms
  • Monosaccharide Transport Proteins
  • Luciferases
  • Insulinoma