Post-operative effects on insulin resistance and specific tension of single human skeletal muscle fibres

1999 ◽  
Vol 97 (4) ◽  
pp. 449-455 ◽  
Author(s):  
Hans DEGENS ◽  
Mattias SOOP ◽  
Peter HÖÖK ◽  
Olle LJUNGQVIST ◽  
Lars LARSSON

Surgery and accidental trauma are associated with a transient period of insulin resistance, substrate catabolism and muscle weakness. In the present study, we evaluated the changes in the force-generating capacity of chemically skinned single muscle fibres following abdominal surgery. Biopsies of the m. vastus lateralis were obtained in three patients 1 day before and 3 or 6 days after surgery. Part of the biopsy was frozen for histochemical analysis of the fibre cross-sectional area (FCSA) and myofibrillar protein content, and another part was used for single-fibre contractile measurements. All patients developed insulin resistance following surgery. The maximum velocity of unloaded shortening of single muscle fibres did not change following surgery. The FCSA did not decrease after surgery, as determined either from histochemical sections or from single fibres measured at a fixed sarcomere length of 2.76±0.09 μm (mean±S.D.). Further, the force-generating capacity of the single fibres, measured as maximal Ca2+-activated force (P0) or as P0 normalized to FCSA (specific tension), remained unchanged, as did the myofibrillar protein content of the muscle. In conclusion, the muscle weakness associated with post-operative insulin resistance is not related to a decreased specific tension or a loss of myofibrillar proteins. Other potential cellular mechanisms underlying post-operative weakness are discussed.

1985 ◽  
Vol 365 (1) ◽  
pp. 147-163 ◽  
Author(s):  
K A Edman ◽  
C Reggiani ◽  
G te Kronnie

1999 ◽  
Vol 97 (4) ◽  
pp. 449 ◽  
Author(s):  
Hans DEGENS ◽  
Mattias SOOP ◽  
Peter HÖÖK ◽  
Olle LJUNGQVIST ◽  
Lars LARSSON

2001 ◽  
Vol 109 (5) ◽  
pp. 410-417 ◽  
Author(s):  
R.T. Jaspers ◽  
H.M. Feenstra ◽  
M.B.E. Lee-de Groot ◽  
P.A. Huijing ◽  
W.J. van der Laarse

1992 ◽  
Vol 448 (1) ◽  
pp. 511-523 ◽  
Author(s):  
A S Nagesser ◽  
W J van der Laarse ◽  
G Elzinga

1986 ◽  
Vol 7 (4) ◽  
pp. 327-332 ◽  
Author(s):  
N. A. Curtin ◽  
J. V. Howarth ◽  
J. A. Rall ◽  
M. G. A. Wilson ◽  
R. C. Woledge
Keyword(s):  

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ellen Jackson ◽  
Elizabeth Rendina-Ruedy ◽  
Matt Priest ◽  
Brenda Smith ◽  
Veronique Lacombe

Diabetes mellitus is an epidemic disease characterized by alterations in glucose transport, which is tightly regulated by a family of specialized proteins called the glucose transporters (GLUTs). Although diabetic cardiomyopathy is a common complication in diabetic patients, its pathogenesis is still not well understood. Toll-like receptor (TLR) 4, which plays a central role in pathogen recognition by the innate immune system, may also play a critical role in linking inflammation and metabolic disease. We hypothesized that TLR4 activation triggers cardiac insulin resistance. We used mice with a loss-of function mutation in TLR4 (C3H/HeJ) and age-matched wild-type (WT, C57BL/6N) mice (n=8/group) to investigate how feeding a high-fat diet (HFD, 60% kcal from fat) for 16 weeks affected whole-body and cardiac glucose metabolism. After 16 weeks, WT mice fed a HFD were obese and developed hyperglycemia and insulin resistance compared to WT mice on a control diet (10% kcal from fat). The C3H/HeJ mice were partially protected against HFD-induced obesity and insulin resistance. In the heart, WT mice fed a HFD had a 30% decrease (P<0.05) in GLUT4 protein content as measured by Western Blot of cardiac crude membrane protein extracts. In contrast, the loss-of-function point mutation in TLR4 partially rescued cardiac GLUT4 content in the face of a HFD. Interestingly, there was a 40% increase (P<0.05) in the novel GLUT isoform, GLUT8, in the heart when mice of either genotype were fed a HFD. Additionally, GLUT4 protein content was negatively (P<0.05) correlated with GLUT8 content in the myocardium, suggesting that GLUT8 may act as a compensatory mechanism in the face of HFD-induced GLUT4 downregulation. Phosphorylated Akt, a key protein of the insulin signaling pathway, was positively (P<0.05) correlated with GLUT4 content, while the basal/inactive form was negatively correlated. In conclusion, these data suggest that activation of TLR4 activation during diabetes and obesity alters glucose transport by an Akt mechanism, and as such is a pathogenic factor during peripheral and cardiac insulin resistance. Overall, TLR4 appears to be a key modulator in the cross-talk between inflammatory and metabolic pathways, as well as a potential therapeutic target for diabetes.


Sign in / Sign up

Export Citation Format

Share Document