Effects of dapagliflozin and/or insulin glargine on beta cell mass and hepatic steatosis in db/db mice

Objective: To explore the beneficial effects of dapagliflozin and/or insulin glargine on the pancreatic beta cell mass and hepatic steatosis in db/db mice. Methods: Six-week-old db/db mice were assigned to one of four groups: untreated (Placebo), treated with dapagliflozin (Dapa), treated with insulin glargine (Gla), or treated with dapagliflozin and insulin glargine (Dapa+Gla). After 8 weeks of treatment, we determined glucose tolerance, beta cell mass, hepatic lipid content and gene expression. Results: Glucose tolerance was significantly ameliorated in the three treated groups to the same degree compared with the Placebo group. Immunohistochemical analysis revealed that the pancreatic beta cell mass was significantly maintained in the Dapa and Dapa+Gla groups, but not in the Gla group, compared with the Placebo group (Placebo 2.25 +/- 1.44 mg, Dapa 5.01 +/- 1.63 mg, Gla 3.79 +/- 0.96 mg, Dapa+Gla 5.19 +/- 1.78 mg). However, the triglyceride content of the liver was markedly elevated in the Gla group compared with that in the other three groups (Placebo 24.1 +/- 11.5 mg, Dapa 30.6 +/- 12.9 mg, Gla 128 +/- 49.7 mg, Dapa+Gla 54.4 +/- 14.1 mg per gram liver). The expression levels of genes related to fatty acid synthesis and lipid storage were significantly upregulated in the Gla group. Conclusions: Our results showed that beta cell mass was sustained and hepatic steatosis was prevented, after 8weeks of treatment with either dapagliflozin or dapagliflozin plus insulin glargine, but not with insulin glargine alone, in db/db mice. (C) 2019 Elsevier Inc. All rights reserved.