Pretranslational suppression of a glucose transporter protein causes insulin resistance in adipocytes from patients with non-insulin-dependent diabetes mellitus and obesity

A major portion of insulin-mediated glucose uptake occurs via the translocation ofGLUT 4 glucose transporter proteins from an intracellular depot to the plasma membrane. We have exam-ined gene expression for the GLUT 4 transporter isoform in subcutaneous adipocytes, a classic insulin target cell, to better understand molecular mechanisms causing insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) and obe-sity. In subgroups of lean (body mass index [BMII = 24±1) and obese (BMI = 32±2) controls and in obese NIDDM (BMI = 35±2) patients, the number of GLUT 4 glucose transporters was measured in total postnuclear and subcellular membrane fractions using specific antibodies on Western blots. Relative to lean controls, the cellular content of GLUT 4 was decreased 40 % in obesity and 85 % in NIDDM in total cellular mem