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PMID: 1309953 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Engineering of glucose-stimulated insulin secretion and biosynthesis in non-islet cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 2 ·1992-01-15 ·Pages 688-92

Hughes SD, Johnson JH, Quaade C, Newgard CB

Abstract

The high-capacity glucose transporter known as GLUT-2 and the glucose phosphorylating enzyme glucokinase are thought to be key components of the "glucose-sensing apparatus" that regulates insulin release from the beta cells of the islets of Langerhans in response to changes in external glucose concentration. AtT-20ins cells are derived from anterior pituitary cells and are like beta cells in that they express glucokinase and have been engineered to secrete correctly processed insulin in response to analogs of cAMP, but, unlike beta cells, they fail to respond to glucose and lack GLUT-2 expression. Herein we demonstrate that stable transfection of AtT-20ins cells with the GLUT-2 cDNA confers glucose-stimulated insulin secretion and glucose regulation of insulin biosynthesis and also results in glucose potentiation of the secretory response to non-glucose secretagogues. This work represents a first step toward creation of a genetically engineered "artificial beta cell."

MeSH Terms
Adrenocorticotropic Hormone/metabolism Animals Cells, Cultured Gene Expression Glucose/metabolism,pharmacology Glucosephosphates/metabolism In Vitro Techniques Insulin/metabolism Insulin Secretion Monosaccharide Transport Proteins/physiology Pituitary Gland RNA, Messenger/genetics Rats Recombinant Proteins/metabolism Secretory Rate/drug effects Transfection
Chemicals
Glucosephosphates Insulin Monosaccharide Transport Proteins RNA, Messenger Recombinant Proteins Adrenocorticotropic Hormone Glucose
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hughes S D
Center for Diabetes Research, Gifford Laboratories, University of Texas Southwestern Medical Center, Dallas.
Johnson J H
Quaade C
Newgard C B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.2.688
Published
1992-01-15
Pages
688-92
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48304
Subset
IM
Grants
NIDDK NIH HHS · P01-DK42582 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.2.688 PMC Full Text View journal details
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