Skeletal muscle insulin resistance after trauma: insulin signaling and glucose transport.
Surgical trauma induces peripheral insulin resistance; however, the cellular mechanism has not been fully elucidated. We examined the effects of surgical trauma on insulin receptor signaling and glucose transport in skeletal muscle, a tissue that plays a predominant role in maintaining glucose homeostasis. Surgical trauma was induced by intestinal resection in the rat. Receptor phosphorylation was not altered with surgical trauma. Phosphotyrosine-associated phosphatidylinositol (PI) 3-kinase association was increased by 60 and 82% compared with fasted and fed controls, respectively (P < 0. 05). Similar results were observed for insulin receptor substrate-1-associated PI 3-kinase activity. Insulin-stimulated protein kinase B (Akt kinase) phosphorylation was increased by 2.2-fold after surgical trauma (P < 0.05). The hyperphosphorylation of Akt is likely to reflect amplification of PI 3-kinase after insulin stimulation. Submaximal rates of insulin-stimulated 3-O-methylglucose transport were reduced in trauma vs. fasted rats by 51 and 38% for 100 and 200 microU/ml of insulin, respectively (P < 0.05). In conclusion, insulin resistance in skeletal muscle after surgical trauma is associated with reduced glucose transport but not with impaired insulin signaling to PI 3-kinase or its downstream target, Akt. The surgical trauma model presented in this report provides a useful tool to further elucidate the molecular mechanism(s) underlying the development of insulin resistance after surgical trauma.
Strömmer
L
L
Arvid Wretlinds Laboratory for Metabolic and Nutritional Research, Department of Surgery, Karolinska Institute at Huddinge University Hospital, 141 86 Huddinge, Sweden.
Permert
J
J
Arnelo
U
U
Koehler
C
C
Isaksson
B
B
Larsson
J
J
Lundkvist
I
I
Björnholm
M
M
Kawano
Y
Y
Wallberg-Henriksson
H
H
Zierath
J R
JR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004435:Eating; D004837:Epinephrine / Q000097:blood; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D007773:Lactates / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013514:Surgical Procedures, Operative; D014947:Wounds and Injuries / Q000097:blood / Q000503:physiopathology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D007773:Lactates; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose; D006854:Hydrocortisone; D004837:Epinephrine