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
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Mentions: All three of the HFDs used in this study (45% fat, 60% fat, and Western) induced rapid increases in fasting body weight (BW; Figure 1A) and blood glucose levels (Figure 1B) compared with low-fat diet (LFD) controls (10% fat). Moreover, after only 5 days, mice in all three HFD groups were severely glucose intolerant relative to LFD controls (Figure S1A), even though no differences in BW were observed at that time (Figure S1B). At 32 days, HFD mice were both glucose intolerant (Figure S1C) and significantly heavier (Figure S1D) than LFD controls. Mice fed 45% and 60% fat diets were overtly insulin resistant at day 42 (higher glucose levels at 10 and 60–120 min post-insulin, and reduced area above the curve relative to LFD controls), whereas mice on the Western diet only showed significant insulin resistance at 10 min after insulin administration (Figure 1E).
Affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.