Randle cycle

The Randle cycle is a metabolic process involving the competition of glucose and fatty acids for substrates.[1] It is theorized to play a role in explaining type 2 diabetes and insulin resistance.[2][3]

The mechanism involves malonyl-CoA and its inhibition of carnitine palmitoyltransferase I (CPT1). Glucose oxidation produces citrate which can be converted to malonyl-CoA by acetyl-CoA carboxylase (ACC1 or ACC). Malonyl-CoA then can bind to and inhibit one of several tissue-specific CPT1 isoforms. CPT1 is a transporter of long-chain fatty acids at the outer mitochondrial membrane that regulates the rate-controlling step for fatty acid oxidation. Thus, increased glucose oxidation inhibits fatty acid oxidation via malonyl-CoA, which can then be utilized as a substrate for fatty acid synthesis.

It is named for Philip Randle, who described it in 1963.[4]

References

  1. ^ Bevilacqua S, Buzzigoli G, Bonadonna R, et al (1990). "Operation of Randle's cycle in patients with NIDDM". Diabetes 39 (3): 383–9. doi:10.2337/diabetes.39.3.383. PMID 2307295. 
  2. ^ Shuldiner AR, McLenithan JC (2004). "Genes and pathophysiology of type 2 diabetes: more than just the Randle cycle all over again". J. Clin. Invest. 114 (10): 1414–7. doi:10.1172/JCI200423586. PMC 525752. PMID 15545992. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=525752. 
  3. ^ Delarue J, Magnan C (2007). "Free fatty acids and insulin resistance". Current opinion in clinical nutrition and metabolic care 10 (2): 142–8. doi:10.1097/MCO.0b013e328042ba90. PMID 17285001. 
  4. ^ Randle PJ, Garland PB, Hales CN, Newsholme EA (1963). "The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus". Lancet 1 (7285): 785–9. doi:10.1016/S0140-6736(63)91500-9. PMID 13990765.