Influence of insulin and glucose on the functional activity of T-helper-17 in vitro in type 2 diabetes

Influence of insulin and glucose on functional activity of Th17 in vitro was studied. The study included 11 patients with diabetes mellitus type 2 (DM2) and 13 nondiabetic volunteers. Peripheral blood mononuclear cells (PBMC) were cultured for 24 hours in the medium containing 5, 10 and 20 mmol/L of glucose; or the following combinations of insulin and glucose concentrations: 5 mmol/L glucose and 10-10 mol/L insulin, 5 mmol/L glucose and 10-8 mol/L insulin, 20 mmol/L glucose and 10-8 mol/L insulin. Number of active Th17 in culture and quantity of secreted IL17A were estimated. Percentage of Th17 ex vivo was studied in 32 patients with DM2, 12 patients with impaired glucose tolerance (IGT), and in 24 non diabetic healthy volunteers. Patients with IGT were characterized by the elevated number of Th17 ex vivo. PBMC from patients with DM2 revealed enhanced intracellular production of IL17 compared to PBMC from healthy volunteers when cultured in medium with 5 mmol/L glucose for 24 hours. Elevation of glucose content in the medium up to 10 mmol/L caused an increase in spontaneous intracellular production of IL17 both in patients and in healthy volunteers compared to 5 mmol/L glucose. In patients with DM2, cultivation of PBMC with 20 mmol/L of glucose led to the elevation of PMA stimulated intracellular production of IL17 compared to 5 mmol/L glucose. Insulin at all the used concentrations stimulated Th17 in healthy volunteers and in patients with DM2. Intracellular production of IL17 increased in the group of healthy volunteers when the medium was supplied both with 10-8 mol/L insulin and 20 mmol/L glucose. Our study shows that metabolic disturbances during DM2 may be accompanied by the increase of the Th17 functional activity in vitro.