Reduced insulin, GLUT2, and IDX-1 in β-cells after partial pancreatectomy

David H. Zangen*, Susan Bonner-Weir, Chung H. Lee, John B. Latimer, Christopher P. Miller, Joel F. Habener, Gordon C. Weir

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

Reduction of GLUT2 is associated with loss of glucose-induced 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.

Original languageAmerican English
Pages (from-to)258-264
Number of pages7
JournalDiabetes
Volume46
Issue number2
DOIs
StatePublished - Feb 1997
Externally publishedYes

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