Recently, the furan fatty acid metabolite, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) was found to be significantly elevated in the plasma of patients with gestational and T2D. Further studies in animal models revealed a potential causal role of CMPF in diabetes development. However, the timing of the elevation in CMPF, and the role of CMPF in the deterioration of beta cell function during the progression to diabetes, before diabetes onset, has not yet been investigated.
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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