Research Article Details
| Article ID: | A46811 |
| PMID: | 15051828 |
| Source: | J Nutr |
| Title: | Mice heterozygous for Atp10c, a putative amphipath, represent a novel model of obesity and type 2 diabetes. |
| Abstract: | Atp10c is a novel type IV P-type ATPase and is a putative phospholipid transporter. The purpose of this study was to assess the overall effect of the heterozygous deletion of Atp10c on obesity-related phenotypes and metabolic abnormalities in mice fed a high-fat diet. Heterozygous mice with maternal inheritance of Atp10c were compared with heterozygous mice with paternal inheritance of Atp10c and wild-type controls. Body weight, adiposity index, and plasma insulin, leptin and triglyceride concentrations were significantly greater in the mutants inheriting the deletion maternally compared with their sex- and age-matched control male mice fed a 10% fat (% energy) diet and female mice fed a 45% fat (% energy) diet. Glucose and insulin tolerance tests were performed after mice consumed the diets for 4 and 8 wk. Mutants had altered glucose tolerance and insulin response compared with controls, suggesting insulin resistance in both sexes. Mice were killed at 12 wk and routine gross and histological evaluations of the liver, pancreas, adipose tissue, and heart were performed. Histological evaluation showed micro- and macrovesicular lipid deposition within the hepatocytes that was more severe in the mutant mice than in age-matched controls. Although sex differences were observed, our data suggest that heterozygous deletion along with an unusual pattern of maternal inheritance of the chromosomal region containing the single gene, Atp10c, causes obesity, type 2 diabetes, and nonalcoholic fatty liver disease in these mice. |
| DOI: | 10.1093/jn/134.4.799 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |