Obstructive jaundice results in increased liver expression of uncoupling protein 2 and intact skeletal muscle glucose metabolism in the rat.
BACKGROUND
A majority of patients with pancreatic cancer have obstructive jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these patients is associated with significant morbidity. Uncoupling protein 2 (UCP2) has been proposed to regulate energy expenditure and promote liver vulnerability. The effects of obstructive jaundice on muscle glucose metabolism and expression of UCP2 in liver and muscle are unknown.


METHODS
Rats were operated with bile duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and muscle. Simultaneously, insulin-stimulated glucose transport and glycogen synthesis in skeletal muscle were analyzed in vitro.


RESULTS
The jaundiced rats lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold in liver but not in muscle in jaundiced rats compared to pair-fed controls. The jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or enhanced insulin action on skeletal muscle glucose transport and glycogen synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats.


CONCLUSIONS
Experimental obstructive jaundice in the rat is associated with increased liver expression of UCP2, rapid weight loss, and intact insulin action on skeletal muscle glucose metabolism. Obstructive jaundice, by upregulated liver UCP2, may contribute to the cachexia and high surgical morbidity observed in these patients, but not to skeletal muscle insulin resistance in pancreatic cancer patients.
Isaksson
B
B
Dept. of Surgery, Karolinska Institutet at Huddinge University Hospital, Stockholm. Sweden. bengt.isaksson@gastro.hs.sll.se
Rippe
C
C
Simonoska
R
R
Holm
J E
JE
Glaumann
H
H
Segersvärd
R
R
Larsson
J
J
Erlanson-Albertsson
C
C
Permert
J
J
D000818:Animals; D002779:Cholestasis / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000235:genetics* / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D007473:Ion Channels; D008099:Liver / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014475:Uncoupling Agents / Q000378:metabolism*; D000071246:Uncoupling Protein 2; D015431:Weight Loss / Q000235:genetics / Q000502:physiology
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C000604391:Ucp2 protein, rat; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D005947:Glucose