Literature DB >> 10447518

Changes in glucose transport and protein kinase Cbeta(2) in rat skeletal muscle induced by hyperglycaemia.

Y Kawano1, J Rincon, A Soler, J W Ryder, L A Nolte, J R Zierath, H Wallberg-Henriksson.   

Abstract

AIMS/HYPOTHESIS: We have previously reported that hyperglycaemia activates glucose transport in skeletal muscle by a Ca(2+)-dependent pathway, which is distinct from the insulin-signalling pathway. The aim of this study was to explain the signalling mechanism by which hyperglycaemia autoregulates glucose transport in skeletal muscle.
METHODS: Isolated rat soleus muscle was incubated in the presence of various concentrations of glucose or 3-O-methylglucose and protein kinase C and phospholipase C inhibitors. Glucose transport activity, cell surface glucose transporter 1 and glucose transporter 4 content and protein kinase C translocation was determined.
RESULTS: High concentrations of 3-O-methylglucose led to a concentration-dependent increase in [(3)H]-3-O-methylglucose transport in soleus muscle. Dantrolene, an inhibitor of Ca(2+) released from the sarcoplasmic reticulum, decreased the V(max) and the K(m) of the concentration-response curve. Protein kinase C inhibitors (H-7 and GF109203X) inhibited the stimulatory effect of high glucose concentrations on hexose transport, whereas glucose transport stimulated by insulin was unchanged. Incubation of muscle with glucose (25 mmol/l) and 3-O-methylglucose (25 mmol/l) led to a three fold gain in protein kinase Cbeta(2) in the total membrane fraction, whereas membrane content of protein kinase Calpha, beta(1), delta, epsilon and theta were unchanged. A short-term increase in the extracellular glucose concentration did not change cell surface recruitment of glucose transporter 1 or glucose transporter 4, as assessed by exofacial photolabelling with [(3)H]-ATB-BMPA bis-mannose. CONCLUSION/
INTERPRETATION: Protein kinase Cbeta(2) is involved in a glucose-sensitive, Ca(2+)-dependent signalling pathway, which is possibly involved in the regulation of glucose transport in skeletal muscle. This glucose-dependent increase in 3-0-methylglucose transport is independent of glucose transporter 4 and glucose transporter 1 translocation to the plasma membrane and may involve modifications of cell surface glucose transporter activity.

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Year:  1999        PMID: 10447518     DOI: 10.1007/s001250051273

Source DB:  PubMed          Journal:  Diabetologia        ISSN: 0012-186X            Impact factor:   10.122


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