Induction of Energy Expenditure by Sitagliptin Is Dependent on GLP-1 Receptor.
Sitagliptin (SG) increases serum GLP-1 (Glucagon-like peptide-1) through inhibition of the hormone degradation. Resistant starch (RS) induces GLP-1 expression by stimulating L-cells in the intestine. Sitagliptin and resistant starch may have a synergistic interaction in the induction of GLP-1. This possibility was tested in current study in a mouse model of type 2 diabetes. Hyperglycemia was induced in the diet-induced obese mice by a signal injection of streptozotocin (STZ). Sitagliptin (0.4g/100g diet) was tested in the mice (n = 55) with dietary RS (HAM-RS2) at three dosages (0, 15, or 28g/100g diet). Energy and glucose metabolism were monitored in the evaluation of synergistic activity, and GLP-1 activity was determined in the GLP-1 receptor knockout (KO) mice. In the wild type mice, body weight and adiposity were reduced by sitagliptin, which was enhanced by RS (28g). Serum GLP-1 was induced and energy expenditure was enhanced by sitagliptin. Fasting glucose, insulin, and leptin levels were decreased by sitagliptin. The sitagliptin effects were lost in the KO mice (n = 25) although induction of serum GLP-1 by sitagliptin was even stronger in KO mice. The data suggests that sitagliptin is able to reduce adiposity and insulin resistance through induction of energy expenditure. The effect of sitagliptin is partially enhanced by RS. GLP-1 receptor may regulate serum GLP-1 by facilitating the hormone clearance.
Louisiana State University Agricultural Center, Baton Rouge, Louisiana 70803, United States of America.
Felicia
F
Goldsmith
Louisiana State University Agricultural Center, Baton Rouge, Louisiana 70803, United States of America.
Michael J
MJ
Keenan
Louisiana State University Agricultural Center, Baton Rouge, Louisiana 70803, United States of America.
Anne M
AM
Raggio
Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, United States of America.
Xin
X
Ye
Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, United States of America.
Zheng
Z
Hao
Louisiana State University Agricultural Center, Baton Rouge, Louisiana 70803, United States of America.
Holiday
H
Durham
Louisiana State University Agricultural Center, Baton Rouge, Louisiana 70803, United States of America.
James
J
Geaghan
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Weiping
W
Jia
Western Human Nutrition Research Center, Davis, California 95616, United States of America; Department of Food Science and Technology, University of California Davis, Davis, California 95616, United States of America.
Roy J
RJ
Martin
Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, United States of America.
Jianping
J
Ye
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*
D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D000068900:Sitagliptin Phosphate