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Updated: Jul 18, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Non-hypoxic induction of HIF-3alpha by 2-deoxy-D-glucose and insulin
Marc Heidbreder1, Fatimunnisa Qadri, Olaf Jöhren
1Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany. heidbred@medinf.mu-luebeck.de
Abstract:
Hypoxia-inducible factors (HIFs) are key mediators of cellular adaptation to hypoxia, but also respond to non-hypoxic stimuli. To clarify involvement in metabolic disturbances, HIFs were characterised in rats subjected to insulin-induced hypoglycaemia or cellular glucoprivation provoked by 2-deoxy-D-glucose (2-DG). Using real-time qPCR, organ-specific expression of HIF-1alpha, -2alpha, -3alpha, -1beta, and of the target gene GLUT-1 was determined. Distribution of HIF-3alpha proteins was examined by immunohistochemistry. Both, insulin and 2-DG resulted in a widespread increase in HIF-3alpha mRNA. HIF-2alpha mRNA increased in lung and heart after 2-DG only, whereas other HIFs remained unaffected. A pronounced increase of protein levels in cerebral cortex was observed for HIF-3alpha. Functional significance of HIF induction was reflected in enhancement of GLUT-1 mRNA. Transcriptional up-regulation of HIF-3alpha represents a typical response to in vivo hypoglycaemia and glucoprivation. These data suggest an involvement of the HIF system in metabolic derangements as for instance caused by diabetes.
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