Departamento de Fisiología Dr Mauricio Russek, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México, DF, México.
Nutr Res. 2010 Nov;30(11):791-800. doi: 10.1016/j.nutres.2010.10.008.
The levels of circulating nonesterified fatty acids increase during obesity and contribute to insulin resistance by inhibiting insulin-stimulated glucose transport and phosphorylation in human muscles. In cells, glucose-6-phosphate is primarily used in glycogenesis and glycolysis; only 1% to 3% is converted to glucosamine-6-phosphate, which enters the hexosamine-biosynthesis pathway. The major end product of this pathway, uridine-5'-diphosphate-N-acetyl-glucosamine, which is increased by exogenous glucosamine (GlcN) administration, mediates insulin resistance. We hypothesized that the administration of GlcN to rats receiving a high-fat (HF) diet may potentiate the effects of an HF diet on glucose tolerance and other metabolic variables. To evaluate this relationship, 2 groups of rats were fed with a control or HF diet; and another 2 groups received glucosamine hydrochloride at a dose of 500 mg/kg dissolved in drinking water for 21 weeks. Metabolic variables related to insulin resistance were then measured. The levels of blood glucose and serum insulin were higher in a glucose tolerance test in the HF group as compared with the control group. Rats receiving GlcN had reduced liver glycogen and only slightly worsened glucose tolerance as compared with control rats, although this did not induce insulin resistance as evaluated by the homeostasis model assessment. Glucosamine administration was able to partially or completely inhibit some effects of the HF diet by reducing fat depot weight and serum leptin levels, thus resulting in a smaller increase in the insulinemic response to a glucose injection and lower postabsorptive glycemia.
在肥胖症期间，循环非酯化脂肪酸的水平升高，并通过抑制人肌肉中胰岛素刺激的葡萄糖转运和磷酸化来导致胰岛素抵抗。在细胞中，葡萄糖-6-磷酸主要用于糖异生和糖酵解；只有 1%到 3%转化为进入己糖胺生物合成途径的葡萄糖胺-6-磷酸。该途径的主要终产物，尿苷-5'-二磷酸-N-乙酰葡萄糖胺，由外源性葡萄糖胺（GlcN）给药增加，介导胰岛素抵抗。我们假设给接受高脂肪（HF）饮食的大鼠给予 GlcN 可能会增强 HF 饮食对葡萄糖耐量和其他代谢变量的影响。为了评估这种关系，两组大鼠分别用对照或 HF 饮食喂养；另外两组大鼠则连续 21 周每天给予 500mg/kg 盐酸 GlcN 溶于饮用水中。然后测量与胰岛素抵抗相关的代谢变量。与对照组相比，HF 组的葡萄糖耐量试验中血糖和血清胰岛素水平更高。与对照组大鼠相比，给予 GlcN 的大鼠肝糖原减少，仅略微恶化葡萄糖耐量，但通过稳态模型评估并未诱导胰岛素抵抗。GlcN 给药能够通过降低脂肪沉积重量和血清瘦素水平部分或完全抑制 HF 饮食的一些作用，从而导致葡萄糖注射后的胰岛素反应较小和餐后血糖降低。
