Hypoxia inducible factors (HIFs) are master-regulators of cellular responses to hypoxia, and thus are crucial for survival. HIFs also play a role in regulating cellular processes in β-cells, liver, muscle, and adipose tissue, have effects on the regulation of weight, and play a role in type 2 diabetes (T2D). Indeed, in people with T2D the HIF pathway is dyregulated in major metabolic tissues involved in the pathogenesis of diabetes. This review covers the contrasting, complementary and conflicting effects of decreasing and increasing HIFs in various tissues, and shows that a delicate balance exists between HIF levels and optimal metabolic function. We propose that increasing the activity of HIFs might be a potential therapeutic strategy for treating T2D.
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