Analysis of insulin-stimulated insulin receptor activation and glucose transport in cultured skeletal muscle cells from obese subjects.
Obesity is associated with impaired insulin-stimulated glucose disposal in the skeletal muscle, but whether this is an intrinsic or acquired factor is unknown. In many patients with type 2 diabetes mellitus (T2D) and their nondiabetic relatives, who have a genetic predisposition for diabetes, insulin resistance is maintained in cultured muscle cells. To study the association of obesity with defects in insulin action, we investigated insulin stimulation of both insulin receptor (IR) autophosphorylation and subsequent glucose transport in primary skeletal muscle cell cultures obtained from both nonobese and obese nondiabetic subjects. In these 2 groups, there was no difference in the ability of insulin to induce autophosphorylation of the IR, phosphorylation of the downstream serine kinase Akt/PKB, or stimulation of glucose transport. Moreover, there were no major differences in cultured muscle cell content of either the IR, the IR antagonist PC-1, or GLUT 1 and GLUT 4. These data therefore indicate that the insulin resistance associated with obesity is not maintained in cultured muscle cells and suggest that this insulin resistance is an acquired feature of obesity.
Pender
Celia
C
Division of Diabetes and Endocrine Research, Department of Medicine, Mount Zion Medical Center, University of California-San Francisco, Box 1616, San Francisco, CA 94143, USA.
Goldfine
Ira D
ID
Kulp
Jennifer L
JL
Tanner
Charles J
CJ
Maddux
Betty A
BA
MacDonald
Kenneth G
KG
Houmard
Joseph A
JA
Youngren
Jack F
JF
D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D011518:Proto-Oncogene Proteins; D011972:Receptor, Insulin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose