Decreased insulin content and secretion in rin 1046-38 cells overexpressing α a2-adrenergic receptors

M. S. Rodriguez Penn, C. Woodard, R. Collins, Allen M. Spiegel

Research output: Contribution to journalArticle

Abstract

The control of insulin secretion in the cell involves both stimulatory and inhibitory pathways. Gi protein-coupled receptors such as those for galanin, somatostatin or a2 adrenergic agonists, have been found to be normally expressed in islets/ cells where they play an important role in the physiologic inhibition of insulin secretion (1). To study the effect of supraphysiologic expression of an inhibitory receptor in insulin-secreting/ cells we stably transfected expression vectors pREP4 and pCDNA3 containing an epitope tagged a 2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected each overexpressing the a 2a-adrenergic receptor to varying degrees. Cell lines showing the highest level of receptor expression showed significantly reduced insulin content, and reduced basal and stimulated insulin secretion. Pertussis toxin treatment of cells was able to partially reverse the reduced insulin secretory response. Our results suggest that overexpression of a Giprotein-coupled receptor in islets/ cells can impair insulin secretion. Abnormalities in expression or function, e.g. constitutively activating mutations of such receptors could contribute to impaired insulin secretion in type II diabetes. (1). McDdermott, A.M. and Sharp, G.W, 1993. Inhibition of insulin secretion: a fall-safe system. Cell. Signal. 5:. 229.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997
Externally publishedYes

Fingerprint

insulin secretion
adrenergic receptors
Adrenergic Receptors
insulin
secretion
Insulin
receptors
islets of Langerhans
cells
Islets of Langerhans
Cells
cell lines
adrenergic agonists
pertussis toxin
somatostatin
Galanin
noninsulin-dependent diabetes mellitus
Cell Line
Adrenergic Agonists
epitopes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Decreased insulin content and secretion in rin 1046-38 cells overexpressing α a2-adrenergic receptors. / Rodriguez Penn, M. S.; Woodard, C.; Collins, R.; Spiegel, Allen M.

In: FASEB Journal, Vol. 11, No. 9, 1997.

Research output: Contribution to journalArticle

@article{0117a245f0854e3888cc870e3522f2f6,
title = "Decreased insulin content and secretion in rin 1046-38 cells overexpressing α a2-adrenergic receptors",
abstract = "The control of insulin secretion in the cell involves both stimulatory and inhibitory pathways. Gi protein-coupled receptors such as those for galanin, somatostatin or a2 adrenergic agonists, have been found to be normally expressed in islets/ cells where they play an important role in the physiologic inhibition of insulin secretion (1). To study the effect of supraphysiologic expression of an inhibitory receptor in insulin-secreting/ cells we stably transfected expression vectors pREP4 and pCDNA3 containing an epitope tagged a 2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected each overexpressing the a 2a-adrenergic receptor to varying degrees. Cell lines showing the highest level of receptor expression showed significantly reduced insulin content, and reduced basal and stimulated insulin secretion. Pertussis toxin treatment of cells was able to partially reverse the reduced insulin secretory response. Our results suggest that overexpression of a Giprotein-coupled receptor in islets/ cells can impair insulin secretion. Abnormalities in expression or function, e.g. constitutively activating mutations of such receptors could contribute to impaired insulin secretion in type II diabetes. (1). McDdermott, A.M. and Sharp, G.W, 1993. Inhibition of insulin secretion: a fall-safe system. Cell. Signal. 5:. 229.",
author = "{Rodriguez Penn}, {M. S.} and C. Woodard and R. Collins and Spiegel, {Allen M.}",
year = "1997",
language = "English (US)",
volume = "11",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "9",

}

TY - JOUR

T1 - Decreased insulin content and secretion in rin 1046-38 cells overexpressing α a2-adrenergic receptors

AU - Rodriguez Penn, M. S.

AU - Woodard, C.

AU - Collins, R.

AU - Spiegel, Allen M.

PY - 1997

Y1 - 1997

N2 - The control of insulin secretion in the cell involves both stimulatory and inhibitory pathways. Gi protein-coupled receptors such as those for galanin, somatostatin or a2 adrenergic agonists, have been found to be normally expressed in islets/ cells where they play an important role in the physiologic inhibition of insulin secretion (1). To study the effect of supraphysiologic expression of an inhibitory receptor in insulin-secreting/ cells we stably transfected expression vectors pREP4 and pCDNA3 containing an epitope tagged a 2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected each overexpressing the a 2a-adrenergic receptor to varying degrees. Cell lines showing the highest level of receptor expression showed significantly reduced insulin content, and reduced basal and stimulated insulin secretion. Pertussis toxin treatment of cells was able to partially reverse the reduced insulin secretory response. Our results suggest that overexpression of a Giprotein-coupled receptor in islets/ cells can impair insulin secretion. Abnormalities in expression or function, e.g. constitutively activating mutations of such receptors could contribute to impaired insulin secretion in type II diabetes. (1). McDdermott, A.M. and Sharp, G.W, 1993. Inhibition of insulin secretion: a fall-safe system. Cell. Signal. 5:. 229.

AB - The control of insulin secretion in the cell involves both stimulatory and inhibitory pathways. Gi protein-coupled receptors such as those for galanin, somatostatin or a2 adrenergic agonists, have been found to be normally expressed in islets/ cells where they play an important role in the physiologic inhibition of insulin secretion (1). To study the effect of supraphysiologic expression of an inhibitory receptor in insulin-secreting/ cells we stably transfected expression vectors pREP4 and pCDNA3 containing an epitope tagged a 2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected each overexpressing the a 2a-adrenergic receptor to varying degrees. Cell lines showing the highest level of receptor expression showed significantly reduced insulin content, and reduced basal and stimulated insulin secretion. Pertussis toxin treatment of cells was able to partially reverse the reduced insulin secretory response. Our results suggest that overexpression of a Giprotein-coupled receptor in islets/ cells can impair insulin secretion. Abnormalities in expression or function, e.g. constitutively activating mutations of such receptors could contribute to impaired insulin secretion in type II diabetes. (1). McDdermott, A.M. and Sharp, G.W, 1993. Inhibition of insulin secretion: a fall-safe system. Cell. Signal. 5:. 229.

UR - http://www.scopus.com/inward/record.url?scp=33750162514&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750162514&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33750162514

VL - 11

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 9

ER -