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.
Arvid Wretlinds Laboratory for Metabolic and Nutritional Research, Department of Surgery, Karolinska Institute at Huddinge University Hospital, 141 86 Huddinge, Sweden.
L
L
Strömmer
J
J
Permert
U
U
Arnelo
C
C
Koehler
B
B
Isaksson
J
J
Larsson
I
I
Lundkvist
M
M
Björnholm
Y
Y
Kawano
H
H
Wallberg-Henriksson
J R
JR
Zierath
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