title: Glucosamine enhances body weight gain and reduces insulin response in mice fed chow diet but mitigates obesity, insulin resistance and impaired glucose tolerance in mice high-fat diet.
abstract: OBJECTIVE
  This study investigated the potential of glucosamine (GlcN) to affect body weight gain and insulin sensitivity in mice normal and at risk for developing diabetes.
  
  
  METHODS
  Male C57BL/6J mice were fed either chow diet (CD) or a high fat diet (HFD) and the half of mice from CD and HFD provided with a solution of 10% (w/v) GlcN. Total cholesterol and nonesterified free fatty acid levels were determined. Glucose tolerance test and insulin tolerance test were performed. HepG2 human hepatoma cells or differentiated 3T3-L1 adipocytes were stimulated with insulin under normal (5 mM) or high glucose (25 mM) conditions. Effect of GlcN on 2-deoxyglucose (2-DG) uptake was determined. JNK and Akt phosphorylation and nucleocytoplasmic protein O-GlcNAcylation were assayed by Western blotting.
  
  
  RESULTS
  GlcN administration stimulated body weight gain (6.58±0.82 g vs. 11.1±0.42 g), increased white adipose tissue fat mass (percentage of bodyweight, 3.7±0.32 g vs. 5.61±0.34 g), and impaired the insulin response in livers of mice fed CD. However, GlcN treatment in mice fed HFD led to reduction of body weight gain (18.02±0.66 g vs. 16.22±0.96 g) and liver weight (2.27±0.1 vs. 1.85±0.12 g). Furthermore, obesity-induced insulin resistance and impaired Akt insulin signaling in the liver were alleviated by GlcN administration. GlcN inhibited the insulin response under low (5 mM) glucose conditions, whereas it restored the insulin response for Akt phosphorylation under high (25 mM) glucose conditions in HepG2 and 3T3-L1 cells. Uptake of 2-DG increased upon GlcN treatment under 5 mM glucose compared to control, whereas insulin-stimulated 2-DG uptake decreased under 5 mM and increased under 25 mM glucose in differentiated 3T3-L1 cells.
  
  
  CONCLUSIONS
  Our results show that GlcN increased body weight gain and reduced the insulin response for glucose maintenance when fed to normal CD mice, whereas it alleviated body weight gain and insulin resistance in HFD mice. Therefore, the current data support the integrative function of the HBP reflecting the nutrient status of lipids or glucose and further implicate the importance of the pathway in insulin signaling for the regulation of metabolism.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: Department of Life Science, Inha University, Incheon, Republic of Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Endocrinology & Metabolism, Clinical Pharmacology, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Moon-Suk
authors.initials: MS
authors.lastname: Nam
authors.affiliation: Department of Chemistry, Inha University, Incheon, Republic of Korea.
authors.forename: Hyeongjin
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Republic of Korea. Electronic address: iohan@inha.ac.kr.
authors.forename: Inn-Oc
authors.initials: IO
authors.lastname: Han
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D045744:Cell Line, Tumor; D004032:Diet; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000378:metabolism*; D005944:Glucosamine / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000517:prevention & control*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D004041:Dietary Fats; D005944:Glucosamine
keywords: Glucosamine; Insulin resistance; Obesity