Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs.
Bottom Line: Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported.All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks.Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.
Affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.Show MeSH
Related in: MedlinePlus
Mentions: Fasting blood glucose levels were not affected by any of the combination therapies throughout the study duration (Figure S7). At 12 weeks post-transplantation, mice in all HFD sham groups were glucose intolerant compared with LFD controls, regardless of the drug treatment used (Figure 7A). As expected based on our previous cohort, we found no effect of the cell therapy on glucose tolerance at 12 weeks post-transplantation in the HFD-fed mice without drug treatment (Figure 7B), and likewise, the combination with rosiglitazone was also ineffective at this time (Figure 7E). Interestingly, the cell therapy significantly improved glucose tolerance at 12 weeks post-transplantation when combined with either metformin (Figure 7C) or sitagliptin (Figure 7D) treatment. In fact, glycemic control during an oral glucose challenge was indistinguishable between the LFD controls and HFD-fed mice receiving sitagliptin with the cell therapy, with the exception of a marginally higher peak glucose level at 15 min post-gavage (Figure 7D). The improved glucose tolerance in cell transplant recipients from the metformin- and sitagliptin-treated groups was associated with significantly reduced fasting mouse C-peptide levels compared with their respective sham controls at 16 weeks post-transplantation (Figure 7G), an effect that was not yet evident at 4 weeks (Figure 7F). Interestingly, the improvements in glucose tolerance were not associated with differences in glucose-stimulated C-peptide secretion by hESC-derived grafts. All transplant recipients showed robust glucose-responsive human C-peptide secretion at 16 weeks, and there were no differences in human C-peptide levels between HFD-fed mice treated with different antidiabetic drugs (Figure 7H).
Affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.