التفاصيل البيبلوغرافية
| العنوان: |
Global Biochemical Profiling Identifies β-Hydroxypyruvate as a Potential Mediator of Type 2 Diabetes in Mice and Humans. |
| المؤلفون: |
Sheng Zhang, Songyan Wang, Puhl, Matthew D., Jiang, Xuntian, Hyrc, Krzysztof L., Laciny, Erin, Wallendorf, Michael J., Pappan, Kirk L., Coyle, Joseph T., Wice, Burton M. |
| المصدر: |
Diabetes; Apr2015, Vol. 64 Issue 4, p1383-3194, 12p, 2 Color Photographs, 2 Charts, 4 Graphs |
| مصطلحات موضوعية: |
PYRUVATES, KETONIC acids, PYRUVIC acid, TYPE 2 diabetes, DIABETES |
| مستخلص: |
Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are incretins secreted by respective K and L enteroendocrine cells after eating and amplify glucose-stimulated insulin secretion (GSIS). This amplification has been termed the "incretin response." To determine the role(s) of K cells for the incretin response and type 2 diabetes mellitus (T2DM), diphtheria toxin-expressing (DT) mice that specifically lack GIP-producing cells were backcrossed five to eight times onto the diabetogenic NONcNZO10/Ltj background. As in humans with T2DM, DT mice lacked an incretin response, although GLP-1 release was maintained. With high-fat (HF) feeding, DT mice remained lean but developed T2DM, whereas wild-type mice developed obesity but not diabetes. Metabolomics identified biochemicals reflecting impaired glucose handling, insulin resistance, and diabetes complications in prediabetic DT/HF mice. β-Hydroxypyruvate and benzoate levels were increased and decreased, respectively, suggesting β-hydroxypyruvate production from D-serine. In vitro, β-hydroxypyruvate altered excitatory properties of myenteric neurons and reduced islet insulin content but not GSIS. β-Hydroxypyruvate-to-D-serine ratios were lower in humans with impaired glucose tolerance compared with normal glucose tolerance and T2DM. Earlier human studies unmasked a neural relay that amplifies GIP-mediated insulin secretion in a pattern reciprocal to β-hydroxypyruvate-to-D-serine ratios in all groups. Thus, K cells may maintain long-term function of neurons and β-cells by regulating β-hydroxypyruvate levels. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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