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Raleigh, NC, United States

Islet Sciences | Date: 2012-09-28

The invention relates to methods for promoting maturation of islet cells from pre-weaned mammals for the purpose of optimizing the islets for their use as donor tissue for xenotransplantation. The method of the invention removes the pancreas from donor animals and reduces the pancreas tissue to fragments that are greater than the size of an intact islet while retaining islets in their whole, insulin-producing condition. The method of the invention also serially cultures the digested tissue in novel maturation media that enhance the glucose responsiveness of the cultured islets, and selects islets that are sufficiently glucose-responsive for use in transplantation procedures.

The present invention provides novel, biocompatible matrices for cell encapsulation and transplantation. It further provides methods for delivering agents to encapsulated cells and to the local environment of a host system. The invention also provides methods for targeting and manipulating particular cells and/or proteins of the host system. In a composition aspect of the invention, a composition including a collection of capsules is provided. The capsules comprise an inner core, and the inner core is covered by an outer shell composed of a positive polyelectrolyte and a negative polyelectrolyte. The inner core of the capsules contains at least one cell.

Sykes A.P.,Glaxosmithkline | Kemp G.L.,Glaxosmithkline | Dobbins R.,Glaxosmithkline | O'Connor-Semmes R.,Glaxosmithkline | And 4 more authors.
Diabetes, Obesity and Metabolism | Year: 2015

The sodium-dependent glucose transporter 2 (SGLT2) inhibitor remogliflozin etabonate (RE) was evaluated in a 12-week, double-blind, randomized, placebo- and active-controlled, parallel-group study. A total of 252 newly diagnosed and drug-naïve people with type 2 diabetes and glycated haemoglobin (HbA1c) concentrations of 7.0-≤9.5% (53-80mmol/mol) were recruited. Participants were randomized to RE (100, 250, 500 or 1000mg once daily or 250mg twice daily), placebo or 30mg pioglitazone once daily. The primary endpoint was change in HbA1c concentration from baseline. Secondary endpoints included changes in fasting plasma glucose, body weight and lipid profiles, safety and tolerability. We observed a statistically significant trend in the RE dose-response relationship for change from baseline in HbA1c at week 12 (p<0.047). RE was generally well tolerated and no effects on LDL cholesterol were observed. © 2014 John Wiley & Sons Ltd.

Sykes A.P.,Glaxosmithkline | O'Connor-Semmes R.,Glaxosmithkline | Dobbins R.,Glaxosmithkline | Dorey D.J.,Glaxosmithkline | And 4 more authors.
Diabetes, Obesity and Metabolism | Year: 2015

We compared the efficacy of twice-daily doses of remogliflozin etabonate (RE) and once-daily pioglitazone with placebo for reduction in glycated haemoglobin (HbA1c) concentration. In this 12-week, double-blind, randomized, active- and placebo-controlled trial, 336 treatment-naïve subjects with type 2 diabetes and an HbA1c of 7.0-9.5% (53-80mmol/mol) were randomized to RE (50, 100, 250, 500 or 1000mg twice daily), matching placebo or 30mg pioglitazone once daily. The primary endpoint was change in HbA1c from baseline. Other endpoints included changes in body weight, lipid levels, safety and tolerability. RE produced a decreasing dose response in HbA1c at week 12 (p<0.001), with reductions in HbA1c versus placebo ranging from 0.64 to 1.07% (p<0.001). Statistically significant reductions in body weight for RE compared with placebo were also observed. Twice-daily RE resulted in a dose-ordered improvement in glycaemic control and was generally well tolerated. © 2014 John Wiley & Sons Ltd.

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