1. Carnitine in Type 2 Diabetes.
- Author
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MINGRONE, GELTRUDE
- Subjects
CARNITINE ,DIAGNOSIS of diabetes ,CARBOHYDRATE intolerance ,LYSINE ,VITAMIN deficiency ,AMINO acids - Abstract
Carnitine, the L-β-hydroxy-γ-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 β-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 hyper-carnitinemia stimulates nonoxidative glucose disposal during euglycemic hyper-insulinemic 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. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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