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Objective: The aim of this review was to assess the hypothesis that type 1 or 2 diabetes mellitus produced a decrease of brain serotonergic neurotransmission through measurement of plasma free fraction of L-tryptophan (FFT) and intensity-dependence auditory–evoked potentials (IDAEPs). Methods: A diabetic mellitus (DM) model was produced through the administration of streptozotocin. After 7 days, the diabetic rats were divided into two groups. One group was treated with insulin and the other did not receive treatment. Their brainstems were removed to determine: L-tryptophan (L-Trp), 5-hydroxytryptamine (5-HT), and tryptophan-5-hydroxylase activity (TPH), besides its kinetics and activation through phosphorylating conditions. In addition, a series of cross-sectional studies were carried out in patients with diabetes type 1 and 2, with and without depression, in their plasma we determined FFT, and other amino acids unrelated to 5-HT metabolism; glucose and glycosylated hemoglobin. The IDAEP’s N1/P2 components were also determined. Results: A decrease in the synthesis of brain serotonin during the diabetic state was confirmed, due to changes in the kinetics and phosphorylation capacity of TPH and a decreased expression of the THP molecule, which did not return to normal levels with insulin. Also, all diabetic patients showed a significant decrease of FFT in the plasma. The diabetic patients presented an increase in the slope of the amplitude/stimulus intensity function (ASF slope) of the N1/P2 component. It is interesting to mention that the ASF slope was steeper in the diabetic patients with depression in relation to patients diabetic but without depression. Conclusions: The decrease of the FFT in plasma and the increase the N1/P2 component ́s amplitude may reflect a functional relationship between the brain serotonergic tone and the diabetic metabolic changes. The increase of the ASF slope in patients with type 1 diabetes suggest that the response of the auditory cortex to sound intensity stimulus may be regulated by the brain serotonergic activity and that decreased serotonergic neurotransmission may provoke a different behavior of sensory cortices. Therefore, the IDAEP (N1/P2 component) may be an electrophysiological indicator of brain changes of serotonergic neurotransmission in patients with diabetes type 1 and 2. These changes may be related to the psycho-emotional manifestations observed in diabetic children like anxiety and depression.

Clinical and Basic Studies on Diabetes and Brain Serotonin