Decreased hepatic glucose production in obese rats by dipeptidyl peptidase-IV inhibitor sitagliptin / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 1690-1694, 2012.
Article
in English
| WPRIM
| ID: wpr-324908
ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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-(3)H-glucose and (14)C-glycerol as tracers.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pyrazines
/
Triazoles
/
Rats, Sprague-Dawley
/
Therapeutic Uses
/
Drug Therapy
/
Dipeptidyl-Peptidase IV Inhibitors
/
Sitagliptin Phosphate
/
Glucose
/
Liver
/
Metabolism
Limits:
Animals
Language:
English
Journal:
Chinese Medical Journal
Year:
2012
Type:
Article
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