Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and IκB-α

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FIG. 2.
FIG. 2.

a and b: Effect of lipid infusion during a euglycemic-hyperinsulinemic clamp on PKC activity in the membrane (a) and cytosolic (b) fractions of skeletal muscle at 0, ∼2, and ∼6 h. Results are means ± SE of six observations. *P < 0.05 compared with all other observations, and **P < 0.03 compared with values in the same individual at 0 and ∼2 h. c and d: Effect of lipid infusion during a euglycemic-hyperinsulinemic clamp on the distribution of PKC-δ in the membrane (c) and cytosolic (d) fractions of skeletal muscle at 0, ∼2, and ∼6 h.. Muscle biopsies were homogenized, and 50 μg protein/lane was loaded on an 8% SDS-polyacrylamide gel. Blots were probed with PKC-δ polyclonal antibodies. Data were normalized to actin and are presented as means of densitometric units ± SE with n = 6 for all observations. *P < 0.003 compared with biopsies taken at 0 and ∼2 h from the same lipid-infused subjects and at ∼6 h from the glycerol-infused subjects. e and f: Effect of lipid infusion during a euglycemic-hyperinsulinemic clamp on the distribution of PKC-βΙΙ in membrane (e) and cytosolic (f) fractions of skeletal muscle. See legend to panels c and d for details. *P < 0.02 vs. values in biopsies taken at 0 and ∼2 h from the same individuals and ∼6 h from individuals infused with glycerol. g: Effect of lipid infusion during a euglycemic-hyperinsulinemic clamp on DAG (g) and ceramide (h) mass. Lipids were extracted from ∼10 mg muscle from biopsies taken at 0, ∼2, and ∼6 h from subjects infused with either glycerol or lipid. Extracts were run on a TLC plate, incorporation of P32 into DAG, and ceramide was determined. Results are means ± SE (n = 5) for all observations. *P < 0.05 vs. glycerol group at ∼6 h and values from the same subjects at 0 and 2 h. h: Effect of lipid infusion during a euglycemic-hyperinsulinemic clamp on the degradation of IκB-α. Muscle biopsies were homogenized, and 50 μg protein/lane protein of the cytosolic fraction was loaded on a 12% SDS-polyacrylamide gel. Blots were probed with IκB-α polyclonal antibodies. Data are presented as means ± SE (n = 6). *P < 0.02 compared with biopsies taken at ∼6 h from the glycerol-infused subjects and the lipid-infused subjects at the other time points.

This Article

  1. Diabetes vol. 51 no. 7 2005-2011