TY - JOUR
T1 - Decreased hepatic glucose production in obese rats by dipeptidyl peptidase-IV inhibitor sitagliptin
AU - Lu, Ying Li
AU - Zhou, De Quan
AU - Zhai, Hua Ling
AU - Hui, Wu
AU - Guo, Zeng Kui
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Glycerol
KW - Hepatic glucose production
KW - Lipolysis
KW - Obesity
KW - Sitagliptin
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U2 - 10.3760/cma.j.issn.0366-6999.2012.10.003
DO - 10.3760/cma.j.issn.0366-6999.2012.10.003
M3 - Article
C2 - 22800885
AN - SCOPUS:84871685830
SN - 0366-6999
VL - 125
SP - 1690
EP - 1694
JO - Chinese medical journal
JF - Chinese medical journal
IS - 10
ER -