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Induction of Energy Expenditure by Sitagliptin Is Dependent on GLP-1 Receptor.

Goldsmith F, Keenan MJ, Raggio AM, Ye X, Hao Z, Durham H, Geaghan J, Jia W, Martin RJ, Ye J - PLoS ONE (2015)

Bottom Line: Fasting glucose, insulin, and leptin levels were decreased by sitagliptin.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.

View Article: PubMed Central - PubMed

Affiliation: Louisiana State University Agricultural Center, Baton Rouge, Louisiana 70803, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Body weight and adiposity.(A) Body weight of animals in response to treatment by SG and RS. (B) Body fat content as percentage of total weight. (C) Abdominal fat mass. (D) Body weight before treatment. (E) Blood glucose before treatment by SG and RG. The results are expressed as mean ± SEM (n = 9–10). * p<0.05 versus RS alone.
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pone.0126177.g001: Body weight and adiposity.(A) Body weight of animals in response to treatment by SG and RS. (B) Body fat content as percentage of total weight. (C) Abdominal fat mass. (D) Body weight before treatment. (E) Blood glucose before treatment by SG and RG. The results are expressed as mean ± SEM (n = 9–10). * p<0.05 versus RS alone.

Mentions: Sitagliptin was tested in the regulation of adiposity in type 2 diabetes mice, which was generated by a single injection of STZ into diet-induced obese mice. This obese and diabetic model was used in this study to mimic human type 2 diabetes, which is often associated with obesity. Pancreatic islets were partially impaired in the models by STZ to increase blood glucose further in the presence of insulin resistance in DIO mice. It is known that hyperglycemia is not strong in DIO mice. In this mouse model, sitagliptin reduced body weight, body fat content, and visceral fat (Fig 1A–1C). The effect was enhanced by resistant starch at 28% dosage (Fig 1B and 1C). Resistant starch alone did not exhibit an activity in the reduction of body weight, body fat, and visceral fat (Fig 1A–1C). There was no significant difference in body weight and blood glucose between the untreated and treated groups (Fig 1D and 1E). Blood glucose was above 240 mg/dl for qualification of diabetes in mice injected with STZ in this study. Blood glucose is below 100 mg/dl in normal lean mice. The inactivity of resistant starch is likely a result of fermentation inhibition by HFD (data not shown). The data suggest that sitagliptin is able to reduce adiposity and the effect is enhanced by resistant starch.


Induction of Energy Expenditure by Sitagliptin Is Dependent on GLP-1 Receptor.

Goldsmith F, Keenan MJ, Raggio AM, Ye X, Hao Z, Durham H, Geaghan J, Jia W, Martin RJ, Ye J - PLoS ONE (2015)

Body weight and adiposity.(A) Body weight of animals in response to treatment by SG and RS. (B) Body fat content as percentage of total weight. (C) Abdominal fat mass. (D) Body weight before treatment. (E) Blood glucose before treatment by SG and RG. The results are expressed as mean ± SEM (n = 9–10). * p<0.05 versus RS alone.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4418617&req=5

pone.0126177.g001: Body weight and adiposity.(A) Body weight of animals in response to treatment by SG and RS. (B) Body fat content as percentage of total weight. (C) Abdominal fat mass. (D) Body weight before treatment. (E) Blood glucose before treatment by SG and RG. The results are expressed as mean ± SEM (n = 9–10). * p<0.05 versus RS alone.
Mentions: Sitagliptin was tested in the regulation of adiposity in type 2 diabetes mice, which was generated by a single injection of STZ into diet-induced obese mice. This obese and diabetic model was used in this study to mimic human type 2 diabetes, which is often associated with obesity. Pancreatic islets were partially impaired in the models by STZ to increase blood glucose further in the presence of insulin resistance in DIO mice. It is known that hyperglycemia is not strong in DIO mice. In this mouse model, sitagliptin reduced body weight, body fat content, and visceral fat (Fig 1A–1C). The effect was enhanced by resistant starch at 28% dosage (Fig 1B and 1C). Resistant starch alone did not exhibit an activity in the reduction of body weight, body fat, and visceral fat (Fig 1A–1C). There was no significant difference in body weight and blood glucose between the untreated and treated groups (Fig 1D and 1E). Blood glucose was above 240 mg/dl for qualification of diabetes in mice injected with STZ in this study. Blood glucose is below 100 mg/dl in normal lean mice. The inactivity of resistant starch is likely a result of fermentation inhibition by HFD (data not shown). The data suggest that sitagliptin is able to reduce adiposity and the effect is enhanced by resistant starch.

Bottom Line: Fasting glucose, insulin, and leptin levels were decreased by sitagliptin.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.

View Article: PubMed Central - PubMed

Affiliation: Louisiana State University Agricultural Center, Baton Rouge, Louisiana 70803, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus