Affiliation:
1. Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA
Abstract
Reduction of β-cell mass and function is central to the pathogenesis of type 2 diabetes. The terms glucotoxicity, lipotoxicity, and glucolipotoxicity are used to describe potentially responsible processes. The premise is that chronically elevated glucose levels are toxic to β-cells, that elevated lipid levels in the form of circulating free fatty acids (FFA) also have toxic effects, and that the combination of the two, glucolipotoxicity, is particularly harmful. Much work has shown that high concentrations of FFA can be very damaging to β-cells when used for in vitro experiments, and when infused in large amounts in humans and rodents they produce suppression of insulin secretion. The purpose of this Perspective is to raise doubts about whether the FFA levels found in real-life situations are ever high enough to cause problems. Evidence supporting the importance of glucotoxicity is strong because there is such a tight correlation between defective insulin secretion and rising glucose levels. However, there is virtually no convincing evidence that the alterations in FFA levels occurring during progression to diabetes are pathogenic. Thus, the terms lipotoxicity and glucolipotoxicity should be used with great caution, if at all, because evidence supporting their importance has not yet emerged.
Funder
National Institutes of Health
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference59 articles.
1. Wikipedia, s.v. “The Emperor’s New Clothes,” last modified 31 May 2019, 01:55, https://en.wikipedia.org/wiki/The_Emperor%27s_New_Clothes
2. Islet β cell mass in diabetes and how it relates to function, birth, and death;Weir;Ann N Y Acad Sci,2013
3. Type 2 diabetes-a matter of beta-cell life and death;Rhodes;Science,2005
4. Islet beta cell failure in type 2 diabetes;Prentki;J Clin Invest,2006
5. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes;Butler;Diabetes,2003
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