Ameliorative Effects of Oral Glucosamine on Insulin Resistance and Pancreatic Tissue Damage in Experimental Wistar rats on a High-fat Diet.

Hyperlipidemia due to a high-fat diet (HFD) is a risk factor for inducing insulin resistance (IR) and adverse effects on pancreatic ß-cells in obesity and type 2 diabetes mellitus. This relationship may be due to activation of the hexosaminebiosynthesis pathway. Administration of exogenous glucosamine (GlcN) can increase the end product of this pathway (uridine-5'-diphosphate-N-acetyl-glucosamine), which can mediate IR and protein glycosylation. The objective of this study was to evaluate the effects of oral GlcN and HFD on IR and pancreatic histologic damage in a 22 wk study of 4 groups of male Wistar rats: control group with normal chow diet, HFD group (24%. g/g lard), GlcN group (500 mg/kg-1 per day of glucosamine hydrochloride in drinking water) and HFD plus oral GlcN. Metabolic variables related to IR that were measured included triglycerides (TG), free fatty acids (FFAs) and malondialdehyde (MDA). Histopathologic evaluation of the pancreas was also performed. The results showed IR in the HFD group, which had increased pancreatic nuclear pyknosis and vacuolization, with fatty infiltration and structural alteration of the islets of Langerhans. TG, FFAs and MDA were higher in serum and pancreatic tissue as compared with the control group. The GlcN group did not develop IR and had only mild nuclear pyknosis with no significant change in the pancreatic content of TG, FFAs and MDA. However, the combined administration of GlcN and HFD attenuated IR and improved TG, FFAs and MDA levels in serum and pancreatic tissue and the pancreatic histopathologic changes, with no significant differences as compared with the control group. These findings suggest that the oral GlcN at a dose of 500 mg/kg-1 is protective against IR and the pancreatic histologic damage caused by HFD.

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.