Diabetes represents a range of diseases in which metabolic dysfunction damages multiple organ systems including the liver, peripheral nerves, and kidneys. Although the beginning and advancement of these comorbidities are linked with insulin resistance, hyperglycaemia, and dyslipidemia, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes. Serine and glycine are closely related NEAAs whose levels are invariably decreased in patients with metabolic syndrome, but the mechanistic drivers and downstream consequences of this metabotype remain unclear.
Low systemic serine and glycine are also occurring as a hallmark of macular and peripheral nerve disorders. Normalization of serine by dietary supplementation and mitigation of dyslipidemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.
