Glucosamine attenuates increases of intraabdominal fat, serum leptin levels, and insulin resistance induced by a high-fat diet in rats.
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.
Departamento de Fisiología Dr Mauricio Russek, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México, DF, México.
Cornelio
C
Barrientos
Radu
R
Racotta
Lucía
L
Quevedo
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005944:Glucosamine / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D020738:Leptin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015431:Weight Loss
D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D005944:Glucosamine