A potential new role for muscle in blood glucose homeostasis.
The breakdown of tissue glycogen into glucose is critical for blood glucose homeostasis between meals. In the final steps of glycogenolysis, intracellular glucose 6-phosphate (Glc-6-P) is transported into the endoplasmic reticulum where it is hydrolyzed to glucose by glucose-6-phosphatase (Glc-6-Pase). Although the majority of body glycogen is stored in the muscle, the current dogma holds that Glc-6-Pase (now named Glc-6-Pase-alpha) is expressed only in the liver, kidney, and intestine, implying that muscle glycogen cannot contribute to interprandial blood glucose homeostasis. Recently we reported a second Glc-6-P hydrolase, Glc-6-Pase-beta. Glc-6-Pase-beta shares kinetic and structural similarities to Glc-6-Pase-alpha and couples with the Glc-6-P transporter to form an active Glc-6-Pase complex (Shieh, J.-J., Pan, C.-J., Mansfield, B. C., and Chou, J. Y. (2003) J. Biol. Chem. 278, 47098-47103). Here we demonstrate that muscle expresses both Glc-6-Pase-beta and Glc-6-P transporter and that they can couple to form an active Glc-6-Pase complex. Our data suggest that muscle may have a previously unrecognized role in interprandial glucose homeostasis.
Shieh
Jeng-Jer
JJ
Section on Cellular Differentiation, Heritable Disorders Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pan
Chi-Jiunn
CJ
Mansfield
Brian C
BC
Chou
Janice Yang
JY
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D018076:DNA, Complementary / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000096:biosynthesis* / Q000737:chemistry; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D013997:Time Factors
D001786:Blood Glucose; D018076:DNA, Complementary; D019298:Glucose-6-Phosphate; D006003:Glycogen; D005952:Glucose-6-Phosphatase; D005947:Glucose