RESULTS: In this study, L-cells were isolated from a primary intestinal cell line to create suitable target cells for insulin expression studies. The isolated cells displayed L-cell properties and were therefore used as an L-cell surrogate. Next, the isolated L-cells were transfected with the recombinant plasmid consisting of an insulin gene located downstream of the GLP-1 promoter. The secretion tests revealed that an increase in glucose concentration from 5 mM to 25 mM induced insulin gene expression in the L-cells by 2.7-fold. Furthermore, L-cells quickly responded to the glucose stimulation; the amount of insulin protein increased 2-fold in the first 30 minutes and then reached a plateau after 90 minutes.
CONCLUSION: Our data showed that L-cells efficiently produced the mature insulin protein. In addition, the insulin protein secretion was positively regulated with glucose induction. In conclusion, GLP-1 promoter and L-cell could be potential candidates for diabetes gene therapy agents.
AIMS: To examine the trends in prescribed antidiabetic treatments, including variations across age, gender, socioeconomic status and regions in the Irish population over the last 10 years.
METHODS: The Irish national pharmacy claims database was used to identify patients ≥ 16 years dispensed antidiabetic agents (oral or insulin) from January 2003 to December 2012 through the two main community drug schemes for diabetes. The rate of prescribing per 1,000 population was calculated. Logistic regression was used to examine variations in prescribing in patients with diabetes.
RESULTS: There was a significant increase in the prescribing of fast and long-acting insulin analogues with a rapid decline in the prescribing of human insulin (p < 0.0001). Increased prescribing of metformin, incretin modulators and fixed oral combination agents was observed (p < 0.0001). Females and older aged patients were more likely to be prescribed human insulin than other insulins. Metformin was less likely while sulphonylureas were more likely to be prescribed in older than younger aged patients. Socioeconomic differences were observed in increased prescribing of the newer and more expensive antidiabetic agents in the non-means tested scheme. Regional variations were observed in the prescribing of both insulin and oral antidiabetic agents.
CONCLUSION: There has been an increase over time in the prescribing of both insulin and oral antidiabetic agents in the Irish population with increasing uptake of newer antidiabetic agents. This has implications for projecting future uptake and expenditure of these agents given the rising level of diabetes in the population.
METHODS: This study was designed to investigate the effect of SynacinnTM and its individual biomarkers on drug metabolizing enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam), CYP3A4 (Testosteron)), to assess its herb-drug interaction potential through cytochrome P450 inhibition assay. This study was conducted using liquid chromatography- tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron).
RESULTS: Result showed that SynacinnTM at maximum concentration (5000 µg/ml) 100% inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron). IC50 values determined were 0.23, 0.60, 0.47, 0.78, 1.23, 0.99, 1.01, and 0.91 mg/ml for CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 (midazolam) and 3A4 (testosterone), respectively. Meanwhile, all individual biomarkers showed no, less or moderate inhibitory effect towards all the tested CYP450 except for curcumin that showed inhibition of CYP2C8 (91%), CYP2C9 (81%) and CYP2C19 (72%) at 10µM.
CONCLUSION: Curcumin was found to be an active constituent that might contribute to the inhibition of SynacinnTM against CYP2C8, CYP2C9 and CYP2C19. It can be suggested that SynacinnTM can be consumed separately from a drug known to be metabolized by all tested CYP450 enzymes.
RESEARCH DESIGN AND METHOD: We reviewed a number of published articles from 2002 to 2016 to find out the appropriate management of diabetes mellitus. The paramount parameters of the selected studies include the insulin type & its dose, type of diabetes, duration and comparison of different insulin protocols. In addition, various newly developed approaches for insulin delivery with potential output have also been evaluated.
RESULTS: A great variability was observed in managing diabetes mellitus through insulin therapy and the important controlling factors found for this therapy include; dose titration, duration of insulin use, type of insulin used and combination therapy of different insulin.
CONCLUSION: A range of research articles on current trends and recent advances in insulin has been summarized, which led us to the conclusion that multiple daily insulin injections or continuous subcutaneous insulin infusion (insulin pump) is the best method to manage diabetes mellitus. In future perspectives, development of the oral and inhalant insulin would be a tremendous breakthrough in Insulin therapy.
METHODS: Mixed method approach including surveying prescribing practices in hospitals coupled with dispensing practices and prices among community pharmacies and drug stores across Bangladesh. This method was adopted since public hospitals only dispense insulins such as soluble insulins free-of-charge until funds run out and all long-acting insulin analogues have to be purchased from community stores.
RESULTS: There has been growing prescribing and dispensing of long-acting insulins in Bangladesh in recent years, now accounting for over 80% of all insulins dispensed in a minority of stores. This increase has been helped by growing prescribing and dispensing of biosimilar insulin glargine at lower costs than the originator, with this trend likely to continue with envisaged growth in the number of patients. Consequently, Bangladesh can serve as an exemplar to other low- and middle-income countries struggling to fund long-acting insulin analogues for their patients.
CONCLUSIONS: It was encouraging to see continued growth in the prescribing and dispensing of long-acting insulin analogues in Bangladesh via the increasing availability of biosimilars. This is likely to continue benefitting all key stakeholder groups.