Endocrine Abstracts

Physiological role of nerve growth factor (NGF) was characterized for the sensory and vegetative nervous systems, as well as for the central, endocrine and immune systems. The growth simulator and a cytokine, NGF is known to be involved in the metabolism of various pathological conditions. Recent clinical and academic studies among patients with diabetes mellitus, insulin resistance and Alzheimer’s disease have brought to light previously unreported cell and pathological conditions. Relevant epidemiological data can serve as the evidence for close association between cognitive deterioration and diabetes mellitus due to the defective glucose uptake in the neurons for energy generation. Insulin is known to control the synaptic plasticity due to internalization of neuroreceptors. Accordingly, it is of significant interest to find out if there is any association of diabetes mellitus, the body’s failure to produce enough insulin, with the compromised function of neurotrophins. The work was initiated to isolate NGF in blood specimens from patients with type 1 diabetes mellitus.

Materials and methods

Successively, adsorption chromatography on silica glass, gel filtration by means of Toyopearl HW55 resin (Tosoh Bioscience GmbH, Germany), carboxymethylcellulose chromatography and preparative PAGE were used to isolate the NGF fraction from blood serum of diabetics (n = 7) and non-diabetics (n = 7).

Results and discussion

By means of a method for generation of fractions, we compared blood sera from diabetic and non-diabetic donors for neurogrowth activity. The product we isolated is a high molecular weight complex of NGF and protein carrier of globulin nature with disulfide bond and neurite-stimulating activity of 2 × 10² BU/mg of protein, molecular mass of 160 kDa and pI 9.1–9.7. After treatment with dithiothreitol, we got a protein with molecular mass of 15–30 kDa and activity of 6 × 10² BU/mg of protein. All the properties indicated pertinence of the protein to NGF. Major complications, to name the dysfunction and degeneration of various peripheral neurons among them are typical of diabetes mellitus. Sensory impairments prevail; degeneration of small diameter sensory fibers results in major symptoms. Our findings demonstrated that blood serum NGF concentrations in the diabetics were 2.5 times lower than those in the non-diabetics. In diabetes mellitus, key components of the NGF signal pathway are found deregulated, the same goes to production of the NGF-controlled neuromodulators. Insulin therapy facilitated elevation of the regulator’s concentrations, but they did not reach the standard one. This seems to confirm the hypothesis that in diabetes both neuronal and peripheral insulin sensitivity is impaired.