Researchers performed a prospective study examining CMPF levels in human participants during a 5 year follow-up period and studies in prediabetic (high-fat diet, or HFD, and genetically predisposed) animal models to determine whether rapid elevation in plasma CMPF levels participates in the induction of beta cell failure and accelerates the pathological progression of diabetes.
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, authors 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.
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