Decreased hepatic glucose production in obese rats by dipeptidyl peptidase-IV inhibitor sitagliptin.
- Author:
Ying-Li LU
1
;
De-Quan ZHOU
;
Hua-Ling ZHAI
;
Hui WU
;
Zeng-Kui GUO
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Dipeptidyl-Peptidase IV Inhibitors; therapeutic use; Glucose; metabolism; Liver; drug effects; metabolism; Male; Obesity; drug therapy; metabolism; Pyrazines; therapeutic use; Rats; Rats, Sprague-Dawley; Sitagliptin Phosphate; Triazoles; therapeutic use
- From: Chinese Medical Journal 2012;125(10):1690-1694
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDDipeptidyl 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.
METHODSSprague 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-(3)H-glucose and (14)C-glycerol as tracers.
RESULTSGlycerol 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).
CONCLUSIONSGluconeogenesis 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.