A Novel Long-Acting Glucagon-Like Peptide-1 Agonist with Improved Efficacy in Insulin Secretion and beta-Cell Growth

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by cleavage of proglucagon in intestinal L-cells. In the pancreas, GLP-1 stimulates post-prandial insulin secretion, promotes insulin biosynthesis, and improves insulin sensitivity. Because of its insulinotropic activity, GLP-1 has been considered a good candidate drug for treatment of diabetes mellitus. However, clinical use of GLP-1 has been limited by its short half-life, as a result of rapid degradation by dipeptidyl peptidase-IV (DPP-IV). METHODS: We designed a novel GLP-1 analog, Xenopus GLP-1 (xGLP)-E4. The Ala residue in the second position of xGLP was replaced with a Ser residue to increase the half-life in the body. The C-terminal tail of exendin-4 was added to enhance the binding affinity for the GLP-1 receptor (GLP1R). The potency of GLP-1 and its analogs was determined by luciferase assay. The stability of GLP1R agonists was evaluated by determining the activity of agonists that had been preincubated in the presence of fetal bovine serum, which contains innate DPP-IV activity. The effects of xGLP-E4 on insulin secretion and beta-cell growth were investigated using insulin enzyme-linked immunosorbent assay and cell counting. RESULTS: xGLP-E4 exhibited improved stability against DPP-IV activity and increased potency to GLP1R, compared with GLP-1. An increase in glucose-dependent insulin secretion was observed in xGLP-E4-treated pancreatic beta-cells. The effect of xGLP-E4 on beta-cell growth was greater than that of GLP-1. CONCLUSION: We developed a novel GLP-1 analog, xGLP-E4, that shows prolonged longevity and improved efficacy. This analog is a potential candidate for treatment of type 2 diabetes.

The Effect of Chest Physiotherapy on the Amount of Tracheal Secretion and PaO2 / 기본간호학회지

The purpose of this research was to find out the effect of chest physiotherapy on the amount of tracheal secretion and PaO2. After changing position of the neurosurgical patients who had tracheostomy cannula, experimental treatments were applied as bellows, manual chest percussion on group I, chest percussion and manual chest vibration on group II, chest percussion and mechanical chest vibration on group III were done. After these trials, we have analyzed the efficacy of each procedures comparing the group differences in the quantity of tracheal secretion and PaO2. Target samples were sixty patients aged between 20 to 60 who have tracheostomy state and decreased consciousness status that were admitted in NICU of a university hospital from June 1 to August 31, 1999. They assigned randomly into three experimental groups. To compare the effect of each interventions, tracheal secretion quantity was measured and PaO2 was analyzed via arterial blood gas analyzer. The data were analyzed by ANCOVA of 5% significance level using SPSS P/C program. The results were as bellows. 1) The first hypothesis " There is a difference in the quantity of the secretion among Group I, Group II and Group III" was accepted.(F=29.27, p=0.00) 2) The second hypothesis "There is a difference in PaO2 among Group I, Group II and Group III" was rejected.(F=1.71,p=0.19) From this study results, positional change and manual chest vibration including chest percussion were the most effective treatment to get maximum amount of tracheal secretion and it was confirmed that mechanical chest vibration also made much better effect than sole chest percussion method. Therefore, we concluded that the mechanical or manual chest vibration with chest percussion is more effective respiratory care method than the sole chest percussion.