AAT Bioquest

Restriction of Advanced Glycation End Products Improves Insulin Resistance in Human Type 2 Diabetes

With the changes in society we've seen over recent human history, it is only logical that our diets change as well. The introduction of high-fat, high-sugar foods, along with an increasingly sedentary lifestyle, has had numerous effects on human health, one of the most prominent being the rise in Type II diabetes. The logical conclusion to make is that these two phenomena are directly linked, but no such relationship has been emphatically proved. Since the cost of changing ones diet and lifestyle is far less, both physically and monetarily, than drugs and other treatments, there is an obvious desire to establish this link between dietary intake and diabetes. This was the focus of the study by Uribarri et al. from the Mount Sinai School of Medicine in New York.

Fortunately, quite a bit is know about how diabetes develops, and this serves as a useful jumping off point for the study by Uribarri's research team. For example, it is known that insulin action is regulated by silent mating type information regulation 2 homolog SIRT1, a member of the sirtuin 1 family of NAD+ deacetylases, via signaling mediatiors and transcription factors. In patients with diabetes, SIRT1 activity is decreased, as is the activity of advanced glycation end product (AGE) receptor-1 (AGER-1). This is because AGEs are oxidants, and when they are not controlled by AGER1, oxidative stress increases, as well as inflammation. Then, when glycooxidants are introduced while AGER1 is low, it is possible it will have a negative effect on SIRT1, leading to insulin resistance and diabetes. This is the key: what is the link between insulin resistance, dietary AGEs, and diabetes? Uribarri et al. went to find out. Since SIRT1 is in a NAD+ deacetylase, they needed a tool to measure NAD and NADH, for which they used the Amplite Fluorimetric Total NAD and NADH Assay Kit. This assay kit is more accurate than other NAD and NADH assays largely because it uses specific enzymes to recognize NAD/NADH, as opposed to measuring NAD/NADH absorption at 340nm, which is the preferred method of other assay kits. This allows for sensitivity and decreased interference, allowing for more accurate results.

In the end, Uribarri et al. were able to demonstrate that AGE restriction lowers insulin levels, which is a marker of insulin resistance and inflammation. Furthermore, AGER1 and SIRT1 levels were nearly normalized during AGE restriction, suggesting AGEs do in fact have an impact on insulin resistance. This research is invaluable for understanding diabetes and for developing potential therapies, as it sheds light on one of the condition's key processes that was previously a mystery. These results would not have been possible if the tools used did not allow for accurate and reliable measurements. By using the Amplite Fluorimetric Total NAD and NADH Assay Kit, the research team could be sure they were getting the most accurate reading, allowing them to confidently make conclusions that will greatly advance the field of study.



  1. Uribarri, Jaime, et al. "Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1." Diabetes care 34.7 (2011): 1610-1616.

Original created on February 7, 2018, last updated on February 7, 2018
Tagged under: