title: Effects of glucosamine on insulin-stimulated glucose metabolism in rat soleus muscle.
abstract: 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 microU/ml) glucose transport and phosphorylation. The percentage decreases for 3H-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 3H-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 14C-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 microU 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.
authors.affiliation: Department of Biochemistry, University of Oxford, U.K.
authors.forename: C
authors.initials: C
authors.lastname: Fürnsinn
authors.forename: A L
authors.initials: AL
authors.lastname: Sanderson
authors.forename: G K
authors.initials: GK
authors.lastname: Radda
authors.forename: B
authors.initials: B
authors.lastname: Leighton
mesh_terms: D000818:Animals; D001692:Biological Transport; D003847:Deoxyglucose / Q000378:metabolism; D005944:Glucosamine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
chemical_list: D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D006003:Glycogen; D003847:Deoxyglucose; D005947:Glucose; D005944:Glucosamine