Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA.

Abstract

Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression. Increased free fatty acid (FFA) level has been suggested to be responsible for the upregulation. Because these metabolic states are also characterized by insulin deficiency, the present study was designed to examine whether insulin has a significant effect to regulate PDK mRNA expression in rat skeletal muscle. In study 1, overnight-fasted rats received an infusion of saline or insulin for 5 h (n = 6 each). During the insulin infusion, plasma glucose was clamped at basal levels (euglycemic hyperinsulinemic clamp). A third group (n = 6) received Intralipid infusion during the clamp to prevent a fall in plasma FFA. PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion). In contrast, PDK-4 mRNA level was decreased 72% by insulin (P < 0.05), and Intralipid infusion prevented only 20% of the decrease. PDK-4 protein level was decreased approximately 20% by insulin (P < 0.05), but this effect was not altered by Intralipid infusion. In study 2, overnight-fasted rats were refed or received an infusion of saline or nicotinic acid (NA, 30 micromol/h) for 5 h (n = 5 each). During the refeeding and NA infusion, plasma FFA levels were similarly (i.e., 60-70% vs. saline control) lowered. Muscle PDK-4 mRNA level decreased 77% after the refeeding (P < 0.05) but not after the NA infusion. In conclusion, the present data indicate that insulin had a profound effect to suppress PDK-4 expression in skeletal muscle and that, contrary to previous suggestions, circulating FFA had little impact on PDK-4 mRNA expression, at least within 5 h.

• Authors: Felix N Lee, Lihua Zhang, Dan Zheng, Woo S Choi, Jang H Youn
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 287 Issue 1 Pg. E69-74 (Jul 2004) ISSN: 0193-1849 [Print] United States
• PMID: 15026305 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Fat Emulsions, Intravenous
• Fatty Acids, Nonesterified
• Insulin
• Protein Kinases
• pyruvate dehydrogenase kinase 4

Topics

• Animals
• Blood Glucose (analysis)
• Fat Emulsions, Intravenous (administration & dosage)
• Fatty Acids, Nonesterified (blood)
• Glucose Clamp Technique
• Infusions, Intravenous
• Insulin (administration & dosage, blood)
• Insulin Resistance (physiology)
• Male
• Metabolic Clearance Rate
• Muscle, Skeletal (drug effects, enzymology)
• Protein Kinases (metabolism)
• Rats
• Rats, Wistar
• Statistics as Topic