Reduction of GLUT2 is associated with loss of glucoseinduced insulin secretion in genetic and chemical diabetes and in transplanted islets exposed to chronic hyperglycemia. To examine the mechanisms for this loss of GLUT2 in normal islets exposed to hyperglycemia, we performed studies on Sprague Dawley rats 4 weeks after a 90% partial pancreatectomy (Px), a well-characterized model of hyperglycemia. GLUT2 immunofluorescence in the β-cell of Px rats was greatly reduced. Western blot analysis of homogenates of isolated Px islets also showed a reduction in GLUT2 protein; densitometry measurements were 36 ± 3% of values from islets of sham-operated controls. Insulin protein levels were decreased to a similar extent. Islet GLUT2 and insulin mRNA were measured with quantitative reverse transcriptase–polymerase chain reaction. The level of GLUT2 mRNA from Px islets was 24 ± 4% of that of islets from sham-operated controls; similar results were obtained for insulin. Because both these (β-cell–specific messages were reduced, we analyzed the Px islets for the pancreas-duodenum–specific transcription factor IDX-1(IPF-1, STF-1, PDX-1) protein. It was markedly reduced (∼80%) in islets from the Px rats. These data suggest that 1) the loss of GLUT2 protein associated with hyperglycemia is at least partially explained by reduced levels of the GLUT2 gene transcripts; 2) the reduction of β-cell insulin content during chronic hyperglycemia may not be completely due to degranulation (reduced levels of gene transcripts may play a role); and 3) the reduction in the transcription factor IDX-1 raises the possibility that dysregulation of transcription factors may contribute to the abnormal β-cell function found in states of chronic hyperglycemia.
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Original Articles|
February 01 1997
Reduced Insulin, GLUT2, and IDX-1 in β-Cells After Partial Pancreatectomy
David H Zangen;
David H Zangen
E.P. Joslin Laboratories, Joslin Diabetes Center, and the Department of Medicine, Deaconess Hospital and Brigham and Woman's Hospital, Harvard Medical School
Boston
Department of Pediatric Endocrinology, Massachusetts General Hospital, Harvard Medical School
Boston
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Susan Bonner-Weir;
Susan Bonner-Weir
E.P. Joslin Laboratories, Joslin Diabetes Center, and the Department of Medicine, Deaconess Hospital and Brigham and Woman's Hospital, Harvard Medical School
Boston
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Chung H Lee;
Chung H Lee
E.P. Joslin Laboratories, Joslin Diabetes Center, and the Department of Medicine, Deaconess Hospital and Brigham and Woman's Hospital, Harvard Medical School
Boston
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John B Latimer;
John B Latimer
E.P. Joslin Laboratories, Joslin Diabetes Center, and the Department of Medicine, Deaconess Hospital and Brigham and Woman's Hospital, Harvard Medical School
Boston
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Christopher P Miller;
Christopher P Miller
EGRP Group, Genetics Institute Inc
, Cambridge, Massachusetts
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Joel F Habener;
Joel F Habener
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School
Boston
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Gordon C Weir
Gordon C Weir
E.P. Joslin Laboratories, Joslin Diabetes Center, and the Department of Medicine, Deaconess Hospital and Brigham and Woman's Hospital, Harvard Medical School
Boston
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Address correspondence and reprint requests to Dr. David H. Zangen, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: [email protected].
1
J.F.H. is an investigator with the Howard Hughes Medical Institute of Massachusetts General Hospital.
2
FITC, fluorescein isothiocyanate; IDX-1, pancreas-duodenum–specific transcription factor; Px, pancreatectomy; RIA, radioimmunoassay; RTPRC, reverse transcriptase–polymerase chain reaction; ZDF rats, Zucker Diabetic Fatty rats.
Diabetes 1997;46(2):258–264
Article history
Received:
April 29 1996
Revision Received:
September 04 1996
Accepted:
September 04 1996
PubMed:
9000703
Citation
David H Zangen, Susan Bonner-Weir, Chung H Lee, John B Latimer, Christopher P Miller, Joel F Habener, Gordon C Weir; Reduced Insulin, GLUT2, and IDX-1 in β-Cells After Partial Pancreatectomy. Diabetes 1 February 1997; 46 (2): 258–264. https://doi.org/10.2337/diab.46.2.258
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