Roles of interstitial fluid pH in diabetes mellitus: Glycolysis and mitochondrial function

Figure 8 The pH-dependent mechanism of neural cell function in diabetes mellitus with dysfunction of mitochondria. Neural cells with dysfunction of mitochondria synthesize ATP required for maintenance of neural cell function only or mainly via glycolysis. Thus, neural cells with dysfunction of mitochondria produces much larger amounts of H⁺ than neural cells with normal function of mitochondria. H⁺ produced by glycolysis in neural cells with dysfunction of mitochondria[^11,18-20] is released to the extracellular space, lowering pH of interstitial fluids[^15-17] including the fluids in synaptic clefts. Lowered pH of synaptic cleft fluid diminishes the binding affinity of neurotransmitters to their receptors[⁶⁷]. Thus, activity of neural cells is diminished at lowered pH of synaptic cleft fluid. Namely, the amount of neurotransmitters released into the synaptic cleft is large enough for generation of action potential under conditions with normal function of mitochondria. However, the amount of neurotransmitters released into the synaptic cleft is insufficient for generation of action potential under conditions with dysfunction of mitochondria, since lowered pH of synaptic cleft diminishes the binding affinity of neurotransmitters to receptors. Modified from ref.[17] with allowance of free use of figures.