Decreased hepatic glucose production in obese rats by dipeptidyl peptidase-IV inhibitor sitagliptin

Ying Li Lu, De Quan Zhou, Hua Ling Zhai, Wu Hui, Zeng Kui Guo

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background Dipeptidyl peptidase-IV (DPP-4) inhibitors are now used to improve postprandial glycemic control in type 2 diabetes. However, their effects on hepatic glucose production (HGP) in obesity are not clear. This study was designed to test the hypothesis that gluconeogenesis and HGP can be modulated by DPP-4 inhibitors in obesity. Methods Sprague Dawley male rats were divided into four groups, each on a different diet: general rat chow, n=10 (G); G+sitagliptin, n=10; high fat chow (obesity), n=10 (55% fat calories, HFO); HFO+sitagliptin, n=10. After 10 weeks, the rats were fasted overnight and glucose metabolism was determined using 3-3H-glucose and 14C-glycerol as tracers. Results Glycerol rate of appearance (P <0.00001), plasma glycerol (P <0.05) and free fatty acid (FFA) (P <0.05) concentrations, and HGP (P <0.05) were decreased in HFO+sitagliptin group compared with HFO group, but there was no significant difference between G and G+sitagliptin groups (P >0.05). Gluconeogenesis in HFO group was five times of that in G rats (P <0.01), but was significantly declined in HFO+sitagliptin group (P <0.0001). Conclusions Gluconeogenesis and HGP were inhibited by sitagliptin in high fat-induced obese rats due to decreased glycerol availability, which was a result of reduced glycerol release from adipose tissues. The finding suggests that sitagliptin is potentially useful for controlling fasting glucose in obesity, thereby delaying or preventing the development of diabetes.

Original languageEnglish (US)
Pages (from-to)1690-1694
Number of pages5
JournalChinese medical journal
Issue number10
StatePublished - May 2012


  • Glycerol
  • Hepatic glucose production
  • Lipolysis
  • Obesity
  • Sitagliptin

ASJC Scopus subject areas

  • Medicine(all)


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