title: The Effects of Empagliflozin, an SGLT2 Inhibitor, on Pancreatic β-Cell Mass and Glucose Homeostasis in Type 1 Diabetes.
abstract: The novel sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin has recently been reported to improve glycemic control in streptozotocin-induced type 1 diabetic rats in an insulin-independent manner, via an increase in urinary glucose output. We investigated the potential of empagliflozin to recover insulin pathways in type 1 diabetes by improving pancreatic β-cell mass. Blood glucose homeostasis was assessed by an intraperitoneal glucose tolerance test. Serum insulin levels and insulin mRNA expression were determined using commercial insulin ELISA kits and real-time quantitative polymerase chain reaction, respectively. Immunohistochemistry was used to investigate β-cell areas, β-cell proliferation, apoptosis of pancreatic β-cells, and reactive oxygen species production in the pancreatic β-cells. Results showed that glucose tolerance was significantly improved in streptozotocin-induced type 1 diabetic mice treated with empagliflozin. Empagliflozin-treated mice also showed an increase in insulin mRNA expression. Higher serum insulin levels were detected in mice treated with empagliflozin compared with the vehicle group. Immunohistochemistry indicated that β-cell area/total pancreatic area and the expression of cell proliferation marker Ki-67 (co-stained with insulin) were significantly enhanced by empagliflozin treatment. These effects were due, probably, to a reduction in apoptosis and reactive oxygen species in the pancreatic β-cells. Taken together, the results of this study indicate that empagliflozin may have a beneficial effect on preserving β-cell regeneration, thus improving blood glucose homeostasis in type 1 diabetes mellitus, probably via the protection of pancreatic β-cell from glucotoxicity-induced oxidative stress.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
authors.forename: Sam Tsz Wai
authors.initials: ST
authors.lastname: Cheng
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
authors.forename: Stephen Yu Ting
authors.initials: SY
authors.lastname: Li
authors.affiliation: Boehringer-Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Mayoux
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
authors.forename: Po Sing
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006706:Homeostasis; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; C490299:Slc5a2 protein, mouse; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin; D005947:Glucose