Glutamine administration promotes hepatic glucose homeostasis through regulating the PI3K/Akt pathway in high-fat diet-induced obese mice with limb ischemia

Diana Mareta IFA Pitaloka, Chi Hsuan Ko, Ming Tsan Lin, Sung Ling Yeh, Chiu Li Yeh

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)45-53
Number of pages9
JournalNutrition Research
Volume68
DOIs
Publication statusPublished - Aug 1 2019

Keywords

  • Glutamine
  • Hepatic glucose metabolism
  • Limb ischemia
  • Obesity
  • PI3K-Akt pathway

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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