Effect of a cachectic factor on carbohydrate metabolism and attenuation by eicosapentaenoic acid.
The effect of a proteolysis-inducing factor (PIF), produced by cachexia-inducing tumours on glucose utilization by different tissues and the effect of pretreatment with the polyunsaturated fatty acid eicosapentaenoic acid (EPA), has been determined using the 2-deoxyglucose tracer technique. Mice receiving PIF showed a profound depression of body weight (2.3 g) over a 24-h period, which was completely abolished by pretreatment with a monoclonal antibody to PIF or by 3 days pretreatment with EPA at 500 mg kg(-1). Animals receiving PIF exhibited a marked hypoglycaemia, which was effectively reversed by both antibody and EPA pretreatment. There was an increase in glucose utilization by brain, heart and brown fat, but a decrease by kidney, white fat, diaphragm and gastrocnemius muscle after administration of PIF. Changes in organ glucose consumption were attenuated by either monoclonal antibody, EPA, or both. There was a decrease in 2-deoxyglucose uptake by C2C12 myoblasts in vitro, which was attenuated by EPA. This suggests a direct effect of PIF on glucose uptake by skeletal muscle. These results suggest that in addition to a direct catabolic effect on skeletal muscle PIF has a profound effect on glucose utilization during cachexia.
Hussey
H J
HJ
Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Tisdale
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal; D001798:Blood Proteins / Q000494:pharmacology*; D001835:Body Weight; D002100:Cachexia / Q000503:physiopathology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007003:Hypoglycemia; D051379:Mice; D018482:Muscle, Skeletal / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000150:complications; D011509:Proteoglycans
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D011509:Proteoglycans; C042057:proteolysis-inducing peptide; D015118:Eicosapentaenoic Acid; D005947:Glucose