Short-term exposure of high glucose concentrations induces generation of reactive oxygen species in endothelial cells: implication for the oxidative stress associated with postprandial hyperglycemia - Yano et al. (2004)

Key Points

  • Short-term high blood sugar causes oxidative stress

  • Insulin temporarily reduces oxidative stress associated with hyperglycemia

  • Slow breathing can help mitigate the negative effects of hyperglycemia and oxidative stress through its direct antioxidant effect

The Breathing Diabetic Summary

Oxidative stress can be detrimental and cause a whole host of problems.  Unfortunately for us diabetics, chronic high blood sugar is a major cause of oxidative stress (keep reading to see how we can mitigate this problem).  And, this oxidative stress contributes to many diabetic complications.  This paper, however, wanted to examine if even short-term high blood sugar increased oxidative stress.  This is important because people without diabetes still experience short-term postprandial hyperglycemia.

One thing to keep in mind is that this was a cell culture study.  They incubated cells in high glucose concentrations and then measured the production of reactive oxygen species (ROS) over time.  Thus, the results here might not be applicable in the same way within the body where lots of things are going on.  Nevertheless, studies like this are important because they show the mechanisms behind different processes, in this case, ROS production.

They found a significant increase in ROS production after 3 h of incubation in high glucose concentrations.  ROS production continued increasing for 10 h.  They also found that the ROS production occurred in the same way as it occurs in diabetics suffering from chronic hyperglycemia.  In all, the main finding was that even short bouts of high blood sugar cause oxidative stress.

They also looked at how insulin affected this process.  Interestingly, when physiological levels of insulin were present, ROS production was reduced within the first hour of hyperglycemia exposure.  However, after 3 hours, ROS production increased when insulin was present.  This makes sense to me because insulin would remove the hyperglycemia within an hour in the human body, so 3 hours of both hyperglycemia and insulin is unrealistic.  The authors found that the reduction in ROS production during the first hour when insulin was present was due to the generation of nitric oxide (NO).  Insulin is known to stimulate NO production, and NO is able to scavenge superoxide, thus reducing oxidative stress.  The benefits of NO seem to never end

Overall, this study highlights one of the many negative side effects of high blood sugar: increased oxidative stress.  They found that even a short bout of hyperglycemia can increase oxidative stress.  However, there is good news.  Although we might not be able to ever completely eliminate high blood sugars as diabetics (until it is cured!), we know we have a way to mitigate the oxidative stress.  Slow breathing has been shown to have a direct antioxidant effect.  Slow breathing also has been shown to reduce postprandial glucose concentrations.  Taken together, we see that slow breathing has the capability to reduce hyperglycemia and mitigate its associated oxidative stress.  Let’s start practicing Principle 1 today to improve our short-term oxidative stress and reduce the long-term complications it causes us down the road.

Abstract from Paper

Recent studies demonstrating a close relationship between postprandial hyperglycemia and the incidence of atherosclerotic cardiovascular disease prompted us to investigate the generation and source of reactive oxygen species (ROS) in endothelial cells stimulated by short-term exposure to a high glucose concentration. In addition, we investigated the effect of insulin on ROS production induced by high glucose concentration. Cultured bovine aortic endothelial cells demonstrated a significant increase in intracellular ROS generation after a 3-h exposure to 25 mM glucose (131.4% versus 5 mM glucose). This increased generation of ROS was suppressed by an inhibitor of NAD(P)H oxidase. Intracellular ROS production in cells exposed to 3 h of high glucose concentration was increased significantly by the presence of a physiological concentration of insulin. However, after a 1-h exposure to high glucose levels, ROS generation in cells incubated with insulin was only about 80% of that measured in cells incubated without insulin. The generation of intracellular nitric oxide (NO) resulting from an acute insulin effect may account for this difference. In conclusion, acute hyperglycemia itself may possibly cause endothelial oxidative stress in patients with postprandial hyperglycemia. Endothelial oxidative stress may be determined by the interaction between NO and superoxide generation.

Journal Reference:

Miho Yano, Goji Hasegawa, Michiyo Ishii, Masahiro Yamasaki, Michiaki Fukui, Naoto Nakamura, and Toshikazu Yoshikawa, (2004) Short-term exposure of high glucose concentrations induces generation of reactive oxygen species in endothelial cells: implication for the oxidative stress associated with postprandial hyperglycemia, Redox Report: Communications in free radical research, 9:2, 111-116, DOI: 10.1179/135100004225004779.