https://scholars.lib.ntu.edu.tw/handle/123456789/477404
Title: | Glutamine administration promotes hepatic glucose homeostasis through regulating the PI3K/Akt pathway in high-fat diet-induced obese mice with limb ischemia | Authors: | Pitaloka D.M.I. Ko C.-H. MING-TSAN LIN Yeh S.-L. Yeh C.-L. |
Keywords: | Glutamine; Hepatic glucose metabolism; Limb ischemia; Obesity; PI3K-Akt pathway | Issue Date: | 2019 | Publisher: | Elsevier Inc. | Journal Volume: | 68 | Start page/Pages: | 45-53 | Source: | Nutrition Research | Abstract: | High-fat diet-induced obesity can lead to hepatic insulin resistance (IR) and alter glucose metabolism. The decreased protein expression involved in the PI3K-Akt pathway may enhance hepatic glycogenolysis and gluconeogenesis. Obesity-associated glucose dysregulation and IR are risk factors for the development of peripheral arterial disease. Glutamine (Gln) has immunomodulatory properties and was found to attenuate IR and hyperglycemia in diabetic condition. Thus, in this study we hypothesized that Gln administration modulates hepatic glucose metabolism and improve IR via PI3K-Akt pathway in obese mice with limb ischemia. Mice were divided into a high-fat group (HC), and a high-fat Gln group (HG). Mice in the HC group were fed the high-fat diet for 8 weeks, while the HG group was initially fed the high-fat diet for 4 weeks followed by a high-fat diet with Gln for an additional 4 weeks. Part of the mice in the HC and HG groups were subjected to a limb ischemic operation and were euthanized after the operation. Liver tissues and blood samples were collected for analysis. The results showed that high-fat diet-induced obesity resulted in increased plasma glucose and insulin levels. Also, impairment of hepatic insulin signaling by downregulating PI3K-Akt pathway-associated protein expression was observed. Administration of Gln increased protein expression associated with PI3K-Akt signaling pathway, while reducing G6PC and FOXO1 expression in the hepatocytes that may promote glycogen synthesis and inhibit gluconeogenesis. These findings suggest that obese mice treated with Gln-containing high-fat diet may normalize blood glucose and improve IR in response to limb ischemia. ? 2019 Elsevier Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070533801&doi=10.1016%2fj.nutres.2019.05.008&partnerID=40&md5=4b7be8d7720e931045adbe8966ff50f6 https://scholars.lib.ntu.edu.tw/handle/123456789/477404 |
ISSN: | 0271-5317 | DOI: | 10.1016/j.nutres.2019.05.008 | SDG/Keyword: | glucose; glucose 6 phosphatase; glutamine; insulin; phosphoenolpyruvate carboxykinase (GTP); pyruvate carboxylase; transcription factor FKHR; Foxo1 protein, mouse; glucose; glucose 6 phosphatase; glutamine; insulin; phosphatidylinositol 3 kinase; protein kinase B; transcription factor FKHR; animal cell; animal experiment; animal model; animal tissue; Article; blood sampling; body weight; C57BL 6 mouse; controlled study; diet induced obesity; diet supplementation; down regulation; epididymal weight; gluconeogenesis; glucose blood level; glucose homeostasis; glycogen synthesis; insulin blood level; insulin resistance; limb ischemia; lipid diet; liver cell; liver metabolism; liver tissue; liver weight; male; metabolic regulation; mouse; nonhuman; organ weight; Pi3K/Akt signaling; priority journal; protein expression; treatment duration; adverse event; animal; blood; C57BL mouse; drug effect; homeostasis; insulin resistance; ischemia; limb; lipid diet; liver; metabolism; obesity; signal transduction; vascularization; Animals; Blood Glucose; Diet, High-Fat; Extremities; Forkhead Box Protein O1; Glucose; Glucose-6-Phosphatase; Glutamine; Homeostasis; Insulin; Insulin Resistance; Ischemia; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction |
Appears in Collections: | 醫學系 |
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