Novel insulin sensitizer MSDC-0602K improves insulinemia and fatty liver disease in mice, alone and in combination with liraglutide.
Novel insulin sensitizer MSDC-0602K improves insulinemia and fatty liver disease in mice, alone and in combination with liraglutide.
复制标题
DOI：
10.1016/j.jbc.2021.100807
复制
发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
McCommis KS
中科院分区：
文献类型：
--
作者：
Kamm DR;Pyles KD;Sharpe MC;Healy LN;Colca JR;McCommis KS
Insulin sensitizers and incretin mimetics are antidiabetic agents with vastly different mechanisms of action. Thiazolidinedione (TZD) insulin sensitizers are associated with weight gain, whereas glucagon-like peptide-1 receptor agonists can induce weight loss. We hypothesized that combination of a TZD insulin sensitizer and the glucagon-like peptide-1 receptor agonist liraglutide would more significantly improve mouse models of diabetes and nonalcoholic steatohepatitis (NASH). Diabetic db/db and MS-NASH mice were treated with the TZD MSDC-0602K by oral gavage, liraglutide (Lira) by s.c. injection, or combination 0602K+Lira. Lira slightly reduced body weight and modestly improved glycemia in db/db mice. Comparatively, 0602K-treated and 0602K+Lira-treated mice exhibited slight weight gain but completely corrected glycemia and improved glucose tolerance. 0602K reduced plasma insulin, whereas Lira further increased the hyperinsulinemia of db/db mice. Surprisingly, 0602K+Lira treatment reduced plasma insulin and C-peptide to the same extent as mice treated with 0602K alone. 0602K did not reduce glucose-stimulated insulin secretion in vivo, or in isolated islets, indicating the reduced insulinemia was likely compensatory to improved insulin sensitivity. In MS-NASH mice, both 0602K or Lira alone improved plasma alanine aminotransferase and aspartate aminotransferase, as well as liver histology, but more significant improvements were observed with 0602K+Lira treatment. 0602K or 0602K+Lira also increased pancreatic insulin content in both db/db and MS-NASH mice. In conclusion, MSDC-0602K corrected glycemia and reduced insulinemia when given alone, or in combination with Lira. However, 0602K+Lira combination more significantly improved glucose tolerance and liver histology, suggesting that this combination treatment may be an effective therapeutic strategy for diabetes and NASH.
登录
查看更多内容
影响因子：
8.1
作者：
McCommis KS;Hodges WT;Bricker DK;Wisidagama DR;Compan V;Remedi MS;Thummel CS;Finck BN
通讯作者：
Finck BN
影响因子：
7.7
作者：
Donath, MY;Ehses, JA;Reinecke, M
通讯作者：
Reinecke, M
影响因子：
4
作者：
Buganova, Martina;Pelantova, Helena;Haluzik, Martin
通讯作者：
Haluzik, Martin
影响因子：
29
作者：
McCommis KS;Chen Z;Fu X;McDonald WG;Colca JR;Kletzien RF;Burgess SC;Finck BN
通讯作者：
Finck BN
DOI：
10.1002/hep.29025
发表时间：
2017-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
McCommis KS;Hodges WT;Brunt EM;Nalbantoglu I;McDonald WG;Holley C;Fujiwara H;Schaffer JE;Colca JR;Finck BN
通讯作者：
Finck BN