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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/E1051    most recent 00631.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Salinari, S. Articles by Mingrone, G. Search for Related Content PubMed PubMed Citation Articles by Salinari, S. Articles by Mingrone, G.

Dodecanedioic acid overcomes metabolic inflexibility in type 2 diabetic subjects

¹Dipartimento di Informatica e Sistemistica, Università di Roma "La Sapienza," ²Istituto di Analisi dei Sistemi ed Informatica del Consiglio Nazionale delle Ricerche, and ³Istituto di Medicina Interna e Geriatria, Università Cattolica del Sacro Cuore, Rome, Italy

Submitted 12 December 2005 ; accepted in final form 19 June 2006

Metabolically healthy skeletal muscle possesses the ability to switch easily between glucose and fat oxidation in response to homeostatic signals. In type 2 diabetes mellitus and obesity, the skeletal muscle shows a great reduction in this metabolic flexibility. A substrate like dodecanedioic acid (C-12), able to increase skeletal muscle glycogen stores via succinyl-CoA formation, might both postpone the fatigue and increase fatty acid utilization, since it does not affect insulin secretion. In healthy volunteers and in type 2 diabetic subjects, the effect of an oral C-12 load was compared with a glucose or water load during prolonged, moderate-intensity, physical exercise. C-12 metabolism was analyzed by a mathematical model. After C-12, diabetics were able to complete the 2 h of exercise. Nonesterified fatty acids increased both during and after the exercise in the C-12 session. C-12 oxidation provided 14% of total energy expenditure, and the sum of C-12 plus lipids oxidized after the C-12 meal was significantly greater than lipids oxidized after the glucose meal (P < 0.025). The fraction of C-12 that entered the central compartment was 47% of that ingested. During the first phase of the exercise (60 min), the mean C-12 clearance from the central compartment toward tissues was 2.57 and 1.30 l/min during the second phase of the exercise. In conclusion, C-12 seems to be a suitable energy substrate during exercise, since it reduces muscle fatigue, is rapidly oxidized, and does not stimulate insulin secretion, which implies that lipolysis is not inhibited as reported after glucose ingestion.

dodecanedioic acid; energy substrate; physical exercise; mathematical modeling