Previous studies by our group on
mangiferin demonstrated that it exerts an anti‑hyperglycemic effect through the regulation of
cell cycle proteins in 3‑month‑old, partially pancreatectomized (PPx) mice. However, β‑cell proliferation is known to become severely restricted with advanced age. Therefore, it is unknown whether
mangiferin is able to reverse the diabetic condition and retain β‑cell regeneration capability in aged mice. In the present study, 12‑month‑old C57BL/6J mice that had undergone PPx were subjected to
mangiferin treatment (90 mg/kg) for 28 days. Mangiferin‑treated aged mice exhibited decreased
blood glucose levels and increased
glucose tolerance, which was accompanied with higher serum
insulin levels when compared with those in untreated PPx control mice. In addition, islet
hyperplasia, elevated β‑cell proliferation and reduced β‑cell apoptosis were also identified in the mice that received
mangiferin treatment. Further studies on the
mRNA transcript and
protein expression levels indicated comparatively increased levels of cyclins D1 and D2 and cyclin‑dependent kinase 4 in mangiferin‑treated mice, while the levels of p27Kip1 and p16INK4a were decreased relative to those in the untreated PPx controls. Of note,
mangiferin treatment improved the proliferation rate of islet β‑cells in adult mice overexpressing p16INK4a, suggesting that
mangiferin induced β‑cell proliferation via the regulation of p16INK4a. In addition, the
mRNA transcription levels of critical genes associated with insulin secretion, including pancreatic and duodenal homeobox 1,
glucose transporter 2 and
glucokinase, were observed to be upregulated after
mangiferin treatment. Taken together, it was indicated that
mangiferin treatment significantly induced β‑cell proliferation and inhibited β‑cell apoptosis by regulating cell cycle checkpoint
proteins. Furthermore,
mangiferin was also demonstrated to regulate genes associated with insulin secretion. Collectively these, results suggest the therapeutic potential of
mangiferin in the treatment of diabetes in aged individuals.