Subcellular distribution of GLUT 4 in the skeletal muscle of lean type 2 (non-insulin-dependent) diabetic patients in the basal state

Abstract

Insulin resistance of the skeletal muscle is a key feature of Type 2 (non-insulin-dependent) diabetes mellitus. To determine whether a decrease of glucose carrier proteins or an altered subcellular distribution of glucose transporters might contribute to the pathogenesis of the insulin resistant state, we measured glucose transporter numbers in membrane fractions of gastrocnemius muscle of 14 Type 2 diabetic patients and 16 non-diabetic control subjects under basal conditions. Cytochalasin-B binding and immunoblotting with antibodies against transporter-subtypes GLUT 1 and GLUT 4 were applied. The cytochalasin-B binding values (pmol binding sites/g muscle) found in a plasma membrane enriched fraction, high and low density membranes of both groups (diabetic patients and non-diabetic control subjects) suggested a reduced number of glucose transporters in the plasma membranes of the diabetic patients compared to the control subjects (diabetic patients: 1.47 +/- 1.01, control subjects: 3.61 +/- 2.29, p less than or equal to 0.003). There was no clear difference in cytochalasin-B binding sites in high and low density membranes of both groups (diabetic patients: high density membranes 3.76 +/- 1.82, low density membranes: 1.67 +/- 0.81; control subjects: high density membranes 5.09 +/- 1.68, low density membranes 1.45 +/- 0.90). By Western blotting analysis we determined the distribution of the glucose transporter subtypes GLUT 1 and GLUT 4 in the plasma membrane enriched fraction and low density membranes of seven patients of each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms and time course of impaired skeletal muscle glucose transport activity in streptozocin diabetic rats.

“…Theoretically there could be a decrease in transporter number, an impairment in transporter translocation and/or a decrease in transporter intrinsic activity (26). Conflicting data are available on the reduction of GLUT4 content as a mechanism of glucose transport impairment (19)(20)(21)(22)(23)(24)(25). Therefore, a major role could be played by a reduction in the transporter intrinsic activity.…”

“…However, whole muscle GLUT4 content includes both the functionally active transporters located on the plasma membrane and the transporters located in the intracellular microsomal pool, which do not transport glucose into the cell. The few data available on the GLUT4 content in skeletal muscle plasma membranes of diabetic patients are conflicting, showing either a decrease (24) or no change (25). However, skeletal muscle glucose transport can be regulated not only by changes in the number of glucose transporters located on the plasma membrane, but also by changes in their functional activity (26)(27)(28)(29)(30)(31)(32)(33).…”

What we know about facilitative glucose transporters: Lessons from cultured cells, animal models, and human studies

“…Correspondingly the importance of GLUT4 in the maintenance of glucose homeostasis has been determined. In addition, a defect in its distribution or function has been implicated in the development of type 2 diabetes [82,83]. For example, a 90% impairment of insulin-stimulated GLUT4 translocation to the plasma membrane of skeletal muscle of type 2 diabetic subjects compared with normal controls was demonstrated utilizing a biotinylated photoaffinity label [84].…”

Marked depletion of GLUT4 glucose transporters in transverse tubules of skeletal muscle from streptozotocin‐induced diabetic rats

“…Recently, two groups have specifically looked at this possibility in human muscle from NIDDM subjects. Whereas Vogt et al [25] found a 40-50% decrease in GLUT4 in their plasma membrane fraction, Lund et al [26] reported no differences in plasma membrane GLUT4 content between muscles of control and diabetic individuals. However, the possibility that GLUT4 is depleted in muscle transverse tubules of diabetic animals or IDDM and NIDDM subjects remains to be investigated.…”