Carnitine in type 2 diabetes.
Carnitine, the L-beta-hydroxy-gamma-N-trimethylaminobutyric acid, is synthesized primarily in the liver and kidneys from lysine and methionine. Carnitine covers an important role in lipid metabolism, acting as an obligatory cofactor for beta-oxidation of fatty acids by facilitating the transport of long-chain fatty acids across the mitochondrial membrane as acylcarnitine esters. Furthermore, since carnitine behaves as a shuttle for acetyl groups from inside to outside the mitochondrial membrane, it covers also a key role in glucose metabolism and assists in fuel-sensing. A reduction of the fatty acid transport inside the mitochondria results in the cytosolic accumulation of triglycerides, which is implicated in the pathogenesis of insulin resistance. Acute hypercarnitinemia stimulates nonoxidative glucose disposal during euglycemic hyperinsulinemic clamp in healthy volunteers. Similar results were obtained in type 2 diabetic patients. The above findings were confirmed in healthy volunteers using the minimal modeling of glucose kinetics. The total end-clamp glucose tissue uptake was significantly increased by the administration of doses of acetyl-L-carnitine (ALC) from 3.8 to 5.2 mg/kg/min, without a significant dose-response effect. In conclusion, both L-carnitine and ALC are effective in improving insulin-mediated glucose disposal either in healthy subjects or in type 2 diabetic patients. Two possible mechanisms might be invoked in the metabolic effect of carnitine and its derivative: the first is a regulation of acetyl and acyl cellular trafficking for correctly meeting the energy demand; the second is a control action in the synthesis of key glycolytic and gluconeogenic enzymes.
Mingrone
Geltrude
G
Department of Internal Medicine, Catholic University, School of Medicine, 00135 Roma, Italy. gmingrone@rm.unicatt.it
D002331:Carnitine / Q000378:metabolism* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D000074058:Solute Carrier Family 22 Member 5
D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine