Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscle - Azevedo et al. (1995)

Key Points

  • Hypoxia significantly stimulated glucose transport in muscle from lean and obese patients

  • When hypoxia was combined with insulin, muscle glucose transport was significantly increased

  • The glucose transport pathway is still present in muscle of diabetics, even those with insulin resistance, and can be stimulated with hypoxia

The Breathing Diabetic Summary

Let’s first note that this paper was written in 1995 and, based off of the title, we can see that they already knew that hypoxia could stimulate glucose transport in muscle.  In fact, the background material from the introduction indicates that it was known that hypoxia stimulated glucose transport in a similar way that exercise does.  What this study aimed to discover was whether that hypoxia-driven glucose transport was still evident in insulin-resistant muscle.

Jumping straight into their findings, the two takeaway points were (1) that hypoxia stimulates glucose transport in insulin-resistant muscle and (2) that hypoxia + insulin are additive in their stimulating effect of glucose transport, i.e., insulin plus hypoxia will lower blood glucose more than either alone.

For us, the important thing to note is that hypoxia can stimulate glucose transport, even in insulin-resistant muscle (e.g., those with type-2 diabetes).   They also cited a previous study that found that intermittent hypoxia might have the capability to restore insulin sensitivity, a finding that will be confirmed by further research.

The results of this paper really resonated with me and helped me understand how practicing breath holds lowered my blood sugars, even without me knowing it at the time. Additionally, this paper led me down a rabbit hole of research showing that intermittent hypoxia improves glucose tolerance, which eventually led to the development of Principle 3.

Abstract from Paper

Insulin and muscle contraction stimulate glucose transport into muscle cells by separate signaling pathways, and hypoxia has been shown to operate via the contraction signaling pathway. To elucidate the mechanism of insulin resistance in human skeletal muscle, strips of rectus abdominis muscle from lean (body mass index [BMI] <25), obese (BMI >30), and obese non-insulin-dependent diabetes mellitus (NIDDM) (BMI >30) patients were incubated under basal and insulin-, hypoxia-, and hypoxia + insulin-stimulated conditions. Insulin significantly stimulated 2-deoxyglucose transport approximately twofold in muscle from lean (P < 0.05) patients, but not in muscle from obese or obese NIDDM patients. Furthermore, maximally insulin-stimulated transport rates in muscle from obese and diabetic patients were significantly lower than rates in muscle from lean patients (P < 0.05). Hypoxia significantly stimulated glucose transport in muscle from lean and obese patients. There were no significant differences in hypoxia-stimulated glucose transport rates among lean, obese, and obese NIDDM groups. Hypoxia + insulin significantly stimulated glucose transport in lean, obese, and diabetic muscle. The results of the present study suggest that the glucose transport effector system is intact in diabetic human muscle when stimulated by hypoxia.

Journal Reference:
John L. Azevedo, Jr., Julie O. Carey, Walter J. Pories, Patricia G. Morris, and G. Lynis Dohm, (1995), Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscl, Diabetes, 44, 695 – 698.