EFFECTS OF GLUCOSAMINE ON INSULIN-STIMULATED GLUCOSE-METABOLISM IN RAT SOLEUS MUSCLE

Intracellular accumulation of glucosamine metabolites (which can be achieved by pre-incubation of cells with glucosamine) during hyperglycaemia may decrease the rate of insulin-mediated glucose transport in cells. Soleus muscle preparations were pre-incubated in the presence or absence of glucosamine in media that contained glutamine (Dulbecco's modified Eagle medium, DMEM; Medium 199, M199) or devoid of glutamine (Krebs-Henseleit's buffer, KHB). Subsequently, muscles were transferred to fresh media, in the absence of glucosamine, but with various concentrations of insulin and the rates of 2-deoxyglucose transport or intracellular glucose metabolism were measured. Glucosamine pre-exposure decreased both insulin-stimulated (1000 mu U/ml) glucose transport and phosphorylation. The percentage decreases for H-3-2-deoxyglucose transport after pre-incubation with 40 mM glucosamine compared with untreated muscles were: DMEM, 48%; KHB, 50%; M199, 29%. The percentage decreases for H-3-2-deoxyglucose-6-phosphate accumulation were: DMEM, 53%; KHB, 60%; M199, 37%. In DMEM and KHB, glucosamine pre-treatment of soleus muscle preparations markedly decreased the rate of lactate release and stimulated the rate of C-14-glucose incorporation into glycogen. Thus, a distinct shift of glucosyl units from glycolysis to glycogenesis occurred with low and high insulin concentrations, For the latter (1000 mu U of insulin/ml) the ratio of moles of glucose converted to lactate divided by moles of glucose incorporated into glycogen in muscles pre-incubated in the absence or presence of glucosamine (40 mM) was, respectively: DMEM, 4.34+0.52 vs 1.55+0.06, P < 0.001; KHB, 2.80+0.44 vs 0.76+0.03, P < 0.005). Glycogen synthesis was not stimulated in muscles pre-exposed to glucosamine in M199. In muscles pre-incubated to glucosamine and incubated in DMEM or KHB, there was a marked shift of glucose transported into the cell from glycolysis to glycogenesis. Thus, glucosamine or its metabolites had distinct effects on intracellular glucose handling.