Effects of long-term streptozotocin diabetes on cytoskeletal and cytosolic phosphofructokinase and the levels of glucose 1,6-bisphosphate and fructose 2,6-bisphosphate in different rat muscles.
We show here that long-term streptozotocin diabetes affects differently the intracellular distribution of phosphofructokinase (PFK), the rate-limiting enzyme of glycolysis, in tibialis anterior and gastrocnemius muscles. Diabetes, which causes ultrastructural damage in both muscle fibers, induced a decrease in PFK binding to cytoskeleton in gastrocnemius muscle but not in the tibialis anterior muscle. However, the allosteric activity of cytoskeleton-bound and soluble PFK was reduced in both kinds of muscles, most probably due to the decrease in the level of glucose 1,6-bisphosphate, the potent allosteric activator of the enzyme. Levels of fructose 2,6-bisphosphate remained unchanged. A change in the allosteric properties of the cytoskeleton-bound PFK was found only in the diabetic tibialis anterior muscle; in contrast to normal muscle, where only the soluble but not the bound enzyme responded to allosteric effectors, in the diabetic tibialis anterior muscle, the bound enzyme exhibited allosteric properties similar to the soluble enzyme. The reduction in both cytosolic and cytoskeletal PFK, and, thereby, glycolysis in these two kinds of muscles, which results most probably from the reported high pathological intracellular Ca2+ concentration, may contribute to muscle damage in diabetes.
Chen-Zion
M
M
Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Livnat
T
T
Beitner
R
R
D000818:Animals; D003599:Cytoskeleton / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology; D005635:Fructosediphosphates / Q000032:analysis* / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000032:analysis* / Q000378:metabolism; D007328:Insulin / Q000172:deficiency; D008297:Male; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000201:enzymology* / Q000648:ultrastructure; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000494:pharmacology; D013997:Time Factors
D005635:Fructosediphosphates; D005958:Glucosephosphates; D007328:Insulin; D019298:Glucose-6-Phosphate; D013311:Streptozocin; C027652:fructose 2,6-diphosphate; C016473:glucose-1,6-bisphosphate; D010732:Phosphofructokinase-1