1. MAP4K4 and IL-6 + Th17 cells play important roles in non-obese type 2 diabetes.
- Author
-
Chuang HC and Tan TH
- Subjects
- Animals, Asia, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 pathology, Europe, Humans, Mice, Mice, Knockout, Th17 Cells pathology, Diabetes Mellitus, Type 2 immunology, Epigenesis, Genetic immunology, Interleukin-6 genetics, Interleukin-6 immunology, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins immunology, Polymorphism, Single Nucleotide, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases immunology, Th17 Cells immunology
- Abstract
Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6
+ Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.- Published
- 2017
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