Rapid Elevation in CMPF May Act As a Tipping Point in Diabetes Development
| Autor: | Battsetseg Batchuluun, Jakob Bondo Hansen, Judith A. Eversley, Brian J. Cox, Kacey J. Prentice, Katherine Leavey, Ying Liu, Cheng Hu, Weiping Jia, David W. Wei, Michael B. Wheeler, Feihan F. Dai |
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| Rok vydání: | 2016 |
| Předmět: |
Glycation End Products
Advanced Male 0301 basic medicine Beta-cell dysfunction Metabolite Mice chemistry.chemical_compound 0302 clinical medicine Insulin-Secreting Cells Insulin Prediabetes Prospective cohort study lcsh:QH301-705.5 Proinsulin Membrane Potential Mitochondrial chemistry.chemical_classification Middle Aged Endoplasmic Reticulum Stress Tipping point (climatology) Female Glycolysis Adult medicine.medical_specialty 030209 endocrinology & metabolism Diet High-Fat General Biochemistry Genetics and Molecular Biology Prediabetic State 03 medical and health sciences Internal medicine Diabetes mellitus medicine Animals Humans Obesity Furans Pancreas Aged business.industry Fatty acid medicine.disease Disease Models Animal Oxidative Stress Glucose Logistic Models 030104 developmental biology Endocrinology lcsh:Biology (General) Diabetes Mellitus Type 2 Gene Expression Regulation chemistry Propionates Reactive Oxygen Species business |
| Zdroj: | Cell Reports, Vol 14, Iss 12, Pp 2889-2900 (2016) |
| ISSN: | 2211-1247 |
| Popis: | SummaryPrediabetes, a state of mild glucose intolerance, can persist for years before a sudden decline in beta cell function and rapid deterioration to overt diabetes. The mechanism underlying this tipping point of beta cell dysfunction remains unknown. Here, the furan fatty acid metabolite CMPF was evaluated in a prospective cohort. Those who developed overt diabetes had a significant increase in CMPF over time, whereas prediabetics maintained chronically elevated levels, even up to 5 years before diagnosis. To evaluate the effect of increasing CMPF on diabetes progression, we used obese, insulin-resistant models of prediabetes. CMPF accelerated diabetes development by inducing metabolic remodeling, resulting in preferential utilization of fatty acids over glucose. This was associated with diminished glucose-stimulated insulin secretion, increased ROS formation, and accumulation of proinsulin, all characteristics of human diabetes. Thus, an increase in CMPF may represent the tipping point in diabetes development by accelerating beta cell dysfunction. |
| Databáze: | OpenAIRE |
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