Cells In Pathogenesis Of Type Research Articles

Unveiling the role of NK cells, NKT-like cells, and γδ cells in pathogenesis of type 1 reactions in leprosy

Leprosy is a disease with spectral clinical manifestations along with two types of reactions, type 1 reaction (T1R) and type 2 reaction (T2R). T1R especially occurs because of the defensive upgradation of cell-mediated immunity (CMI) to M. leprae antigens. T1R is the main cause of disability in leprosy. The role of conventional adaptive T cells has been well studied to understand T1R. A comprehensive understanding of the role of unconventional T cells in the manifestation of inflammation during T1R is crucial and has not been studied. In our study, we found significantly higher plasma levels of TNFα, IL1β, IL17, and IP10 in T1R when compared to non-reaction (NR). Gene expression for cytokines in blood circulation by qPCR showed significantly higher expression of IFNγ, IP10, TNFα, IL6, IL17A and chemokines CCL3, CCR1, CCR5, and CXCR3 in T1R as compared to NR. Frequencies of NKT-like cells (48.7 %) and NK cells (22.3 %) were found significantly higher in T1R in comparison to NR (36.9 %, 18.3 %, respectively) (p = 0.0001). Significantly lower levels of γδT cells (3.32 %) were observed in T1R in comparison to NR (5.16 %). The present study has provided evidence for the first time on the role of plausible unconventional T cells in the immunopathogenesis of T1R in leprosy.

The effect of metformin and pioglitazone on glucagon of patients with diabetes and metabolic syndrome

Objective To observe and evaluate the effects of metformin and pioglitazone on blood glucose, insulin, glucagon, β-cell function and insulin resistance among patients with diabetes and metabolic syndrome, so as to discuss the role of pancreatic α cells in pathogenesis of type 2 diabetes mainly caused by insulin resistance and the change of α-cell function after treatment. Methods A total of 60 patients diagnosed with diabetes and metabolic syndrome were selected in Beijing Chaoyang District Diabetes Center from April 2012 to April 2013 and divided with random number table into metformin group (treated with metformin 0.5 g orally thrice a day for 1 year, n=30) and pioglitazone group (treated with pioglitazone 15 mg orally once a day for 1 year, n=30). 30 normal healthy people who had physical examination at the Center during the same period were enrolled into the control group, matched in age and gender with the intervention groups. The general condition of the 3 groups, and blood levels of glucose, insulin, and glucagon, insulin sensitivity index (ISI)-Matsuda, homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function index (HOMA-β), 1-phase index, 2-phase index, and insulin secretion sensitivity index (ISSI) at baseline in the 3 groups and after treatment in the metformin group and the pioglitazone group were measured and calculated. Results Compared with the control group before treatment, the intervention groups as a whole had significantly higher fasting glucagon level [(146.22±25.41) pmol/L vs. (21.31±7.85) pmol/L, P=0.002] and area under curve (AUC) of glucagon [(469.84±13.12) pmol/(L·h) vs. (100.94±7.73) pmol/(L·h), P=0.006]. Compared with the results before treatment, the metformin group exhibited significantly reduced fasting glucose [(6.46±1.38) mmol/L vs. (7.54±0.43) mmol/L, P=0.031], fasting insulin [(119.22±69.01) pmol/L vs. (139.38±71.13) pmol/L, P=0.042], fasting glucagon [(91.69±22.11) pmol/L vs. (142.81±24.56) pmol/L, P=0.029], AUC of glucose [(25.19±1.31) mmol/(L·h) vs. (32.68±1.12) mmol/(L·h), P=0.043], AUC of insulin [(468.65±20.10) pmol/(L·h) vs. (786.32±21.37) pmol/(L·h), P=0.017], and AUC of glucagon [(280.60±8.26) pmol/(L·h) vs. (487.14±14.31) pmol/(L·h), P=0.032]; while the pioglitazone group after treatment also showed significantly decreased fasting glucose [(6.58±2.21) mmol/L vs. (7.68±0.59) mmol/L, P=0.028], fasting insulin [(107.92±17.81) pmol/L vs. (144.66±74.43) pmol/L, P=0.033], fasting glucagon [(76.07±20.57) pmol/L vs. (148.34±28.94) pmol/L, P=0.025], AUC of glucose [(25.58±1.22) mmol/(L·h) vs. (35.07±1.38) mmol/(L·h), P=0.038], AUC of insulin [(435.54±19.30) pmol/(L·h) vs. (854.75±20.61) pmol/(L·h), P=0.013], and AUC of glucagon [(223.43±5.83) pmol/(L·h) vs. (458.55±12.96) pmol/(L·h), P=0.026]. The before-after-treatment differences were significantly smaller in the metformin group than in the pioglitazone group in terms of fasting insulin [(20.16±2.98) mmol/L vs. (36.74±2.88) mmol/L, P=0.011], fasting glucagon [(51.12±3.67) pmol/L vs. (72.27±4.58) pmol/L, P=0.016], AUC of insulin [(317.67±13.45) pmol/(L·h) vs. (419.21±15.44) pmol/(L·h), P=0.031] and AUC of glucagon [(206.54±9.66) pmol/(L·h) vs. (235.12±10.29) pmol/(L·h), P=0.046]. Conclusions Glucagon in patients with diabetes and metabolic syndrome is higher than that in normal individuals. Metformin and pioglitazone can decrease the level of glucagon in patients with metabolic syndrome and diabetes as well as improve the glucose control, β-cell function and insulin resistance, suggesting improving effect of these two drugs on α-cell function. Pioglitazone manifests a stronger effect than metformin does. Key words: Metformin; Pioglitazone; Glucagon; Insulin