Research Article Details
| Article ID: | A23715 |
| PMID: | 23544853 |
| Source: | Metab Syndr Relat Disord |
| Title: | Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats. |
| Abstract: | BACKGROUND: Studies investigating the effects of dipeptidyl peptidase-4 inhibitors on hepatic steatosis are lacking. We aimed to determine the effects of sitagliptin on nonalcoholic fatty liver disease (NAFLD) in rats with diet-induced obesity. METHODS: A total of 24 adult female Sprague-Dawley rats, which were 24 weeks old and weighed 199-240 grams, were used. The rats were randomly separated into two groups. The control group (n=6) was fed with standard rat diet; the remaining rats (n=18) were fed with a high-fat diet (HFD) to induce NAFLD. After 12 weeks, rats that were fed with a HFD were randomly separated into two groups: (1) HFD-only group (n=8) was fed with a HFD for an additional 4 weeks, (2) HFD-sitagliptin group (n=10) received sitagliptin (3 mg/kg) for 4 weeks in addition to HFD. At the end of the study (16(th) week), blood samples were drawn from all rats to determine serum glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), and plasma insulin levels. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR) index. Histopathologic evaluation of liver samples was undertaken. RESULTS: The HFD-sitagliptin group had significantly lower serum glucose (140.8±18.8 vs. 224.7±20.6 mg/dL, P<0.001), plasma insulin (15.8±4.4 vs. 28.0±5.9 μIU/L, P<0.001), HOMA-IR index (4.9±1.8 vs. 15.9±2.3, P<0.001), serum triglycerides (199.0±108.7 vs. 468.0±370.7 mg/dL, P<0.001), and cholesterol (82.0±26.7 vs. 90.5±7.0, P<0.001) values compared to the HFD-only group. Hepatic steatosis was significantly less (mean score, 1 vs. 2; P<0.001) in the HFD-sitagliptin group compared to the HFD-only group, whereas there was no difference in hepatic inflammation (P=0.057), liver weight (P=0.068), and ALT levels (P=0.232). CONCLUSION: Sitagliptin may improve hepatic steatosis by increasing insulin sensitivity and improving lipid profiles in rats. |
| DOI: | 10.1089/met.2012.0128 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D338 | Sitagliptin | Chemical drug | DB01261 | DPP4 inhibitor | Antidiabetic drug | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |