30
Views
2
CrossRef citations to date
0
Altmetric
Review

L-carnitine: implications in the treatment of the metabolic syndrome and Type 2 diabetes

Pages 777-783 | Published online: 10 Jan 2014

References

  • Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA287, 356–359 (2002).
  • Abate N, Chandalia M. Ethnicity and Type 2 diabetes: focus on Asian Indians. J. Diabetes Complicat.15, 320–327 (2001).
  • Meigs JB, Wilson PW, Fox CS et al. Body mass index, metabolic syndrome, and risk of Type 2 diabetes or cardiovascular disease. J. Clin. Endocrinol. Metab.91, 2906–2912 (2006).
  • Poobalan A, Aucott L, Smith WC et al. Effects of weight loss in overweight/obese individuals and long-term lipid outcomes – a systematic review. Obes. Rev.5, 43–50 (2004).
  • Lakka HM, Laaksonen DE, Lakka TA et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA288, 2709–2716 (2002).
  • Avramoglu RK, Qiu W, Adeli K. Mechanisms of metabolic dyslipidemia in insulin resistant states: deregulation of hepatic and intestinal lipoprotein secretion. Front. Biosci.8, d464–d476 (2003).
  • Moller DE, Kanfman KD. Metabolic syndrome: a clinical and molecular perspective. Ann. Rev. Med.56, 45–62 (2005).
  • Expert panel report on detection, evaluation and treatment of high blood cholesterol in adults. JAMA285, 2486–2497 (2001).
  • Vaz FM, Wanders RJ. Carnitine biosynthesis in mammals. J. Biol. Chem.361, 417–429 (2002).
  • Calò LA, Pagnin E, Davis PA et al. Antioxidant effect of L-carnitine and its short chain esters: relevance for the protection from oxidative stress related cardiovascular damage. Int. J. Cardiol.107, 54–60 (2006).
  • Gülçin I. Antioxidant and antiradical activities of L-carnitine. Life Sci.78, 803–811 (2006).
  • Conti P, Reale M, Stuard S et al. Reduced human lymphocyte blastogenesis and enhancement of adenosine triphosphate (ATP) by L-carnitine. Mol. Cell. Biochem.31, 1–8 (1994).
  • Virmani A, Gaetani F, Imam S, Binienda Z, Ali S. Possible mechanism for the neuroprotective effects of L-carnitine on methamphetamine-evoked neurotoxicity. Ann. NY Acad. Sci.993, 197–207 (2003)
  • Lohninger A, Pittner G, Pittner F. L-carnitine: new aspects of a known compound – a brief survey. Monatshefte Fur Chemie136, 1255–1268 (2005).
  • Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin. Pharmacol.42, 941–967 (2003).
  • Eder K et al. Free and total carnitine concentrations in pig plasma after oral ingestion of various L-carnitine compounds. Int. J. Vitamin Nutr. Res.75, 3–9 (2007).
  • Poorabbas A, Bagdadchi J, Fallah F et al. Assessment of free L-carnitine levels in Type 2 diabetic women with and without complications. Asia Pac.J. Clin. Nutr.13, S155 (2004).
  • Mamoulakis D, Galanakis E, Dionyssopoulou E, Evangeliou A, Sbyrakis S. Carnitine deficiency in children and adolescents with Type 1 diabetes. J. Diabetes Complicat.18, 271–274 (2004)
  • Ido Y, McHowat J, Chang KC et al. Neural dysfunction and metabolic imbalances in diabetic rats. Prevention by acetyl-L-carnitine. Diabetes43, 1469–1477 (1994).
  • Nakamura J, Koh N, Sakakibara F et al. Polyol pathway hyperactivity is closely related to carnitine deficiency in the pathogenesis of diabetic neuropathy of streptozotocin-diabetic rats. J. Pharmacol. Exp. Ther.287, 897–902 (1998).
  • Petersen KF, Befroy D, Dufour S et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science300, 1140–1142 (2003).
  • Rajasekar P, Anuradha CV. Effect of L-carnitine on skeletal muscle lipids and oxidative stress in rats fed high-fructose diet. Exp. Diabetes Res.2007, 72741–72748 (2007).
  • Sima AA, Calvani M, Mehra M et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care28, 89–94 (2005).
  • De Grandis D, Minardi C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D3, 223–231 (2002).
  • Malone JI, Schocken DD, Morrison AD, Gilbert-Barness E. Diabetic cardiomyopathy and carnitine deficiency. J. Diabetes Complicat.13, 86–90 (1999).
  • Tamamoğullari N, Siliğ Y, Içağasioğlu S, Atalay A. Carnitine deficiency in diabetes mellitus complications. J. Diabetes Complicat.13, 251–253 (1999).
  • Mingrone G, Greco AV, Capristo E et al.L-carnitine improves glucose disposal in type 2 diabetic patients. J. Am. Coll. Nutr.18, 77–82 (1999).
  • De Gaetano A, Mingrone G, Castagneto M, Calvani M. Carnitine increases glucose disposal in humans. J. Am. Coll. Nutr.18, 289–295 (1999).
  • Günal AI, Celiker H, Dönder E, Günal SY. The effect of L-carnitine on insulin resistance in hemodialysed patients with chronic renal failure. J. Nephrol.12, 38–40 (1999).
  • Uzun N, Sarikaya S, Uluduz D, Aydin A. Peripheric and automatic neuropathy in children with Type 1 diabetes mellitus: the effect of L-carnitine treatment on the peripheral and autonomic nervous system. Electromyogr. Clin. Neurophysiol.45, 343–351 (2005).
  • Stephens FB, Constantin-Teodosiu D, Laithwaite D et al. A threshold exists for the stimulatory effect of insulin on plasma L-carnitine clearance in humans. Am. J. Physiol. Endocrinol. Metab.292, E637–E641 (2007).
  • Derosa G, Cicero AF, Gaddi A et al. The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with Type 2 diabetes mellitus. Clin. Ther.25, 1429–1439 (2003).
  • Rahbar AR, Shakerhosseini R, Saadat N et al. Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with Type II diabetes mellitus. Eur. J. Clin. Nutr.59, 592–596 (2005).
  • Solfrizzi V, Capurso C, Colacicco AM et al. Efficacy and tolerability of combined treatment with L-carnitine and simvastatin in lowering lipoprotein(a) serum levels in patients with Type 2 diabetes mellitus. Atherosclerosis188, 455–461 (2006).
  • Ragozzino G, Mattera E, Madrid E et al. Effects of propionyl-carnitine in patients with Type 2 diabetes and peripheral vascular disease: results of a pilot trial. Drugs R D5, 185–190 (2004).
  • Elisaf M, Bairaktari E, Katopodis K et al. Effect of L-carnitine supplementation on lipid parameters in hemodialysis patients. Am. J. Nephrol.18, 416–421 (1998).
  • Carlson LA, Hamsten A, Asplund A. Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid. J. Int. Med.226, 271–276 (1989).
  • Maebashi M, Kawamura N, Sato M, Imamura A, Yoshinaga K. Lipid-lowering effect of carnitine in patients with type-IV hyperlipoproteinaemia. Lancet2, 805–807 (1978).
  • Reaven GM. Banting Lecture 1988. Role of insulin resistance in human disease. Nutrition13, 65 (1997).
  • Bezerra RM, Ueno M, Silva MS, Tavares DQ, Carvalho CR, Saad MJ. A high fructose diet affects the early steps of insulin action in muscle and liver of rats. J. Nutr.130, 1531–1535 (2000).
  • Kelley DE. Influence of weight loss and physical activity interventions upon muscle lipid content in relation to insulin resistance. Curr. Diab. Rep.4, 165–168 (2004).
  • Busserolles J, Gueux E, Rock E, Demigné C, Mazur A, Rayssiguier Y. Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. J. Nutr.133, 1903–1908 (2003).
  • Baciano H, Federico L, Adeli K. Fructose, insulin resistance and metabolic dyslipidemia. Nutr. Metab.21, 5 (2005).
  • Ruderman NB, Saha AK, Vavvas D, Witters LA. Malonyl-CoA, fuel sensing, and insulin resistance. Am. J. Physiol.276, E1–E18 (1999).
  • Schmitz-Peiffer C, Craig DL, Biden TJ. Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J. Biol. Chem.274, 24202–24210 (1999).
  • Lam TK, Carpentier A, Lewis GF et al. Mechanisms of the free fatty acid-induced increase in hepatic glucose production. Am. J. Physiol. Endocrinol. Metab.284, E863–E873 (2003).
  • Kim JK, Wi JK, Youn JH. Plasma free fatty acids decrease insulin stimulated skeletal muscle glucose uptake by suppressing glycolysis in conscious rats. Diabetes45, 446–453 (1996).
  • Barthel A, Nakatani K, Dandekar AA, Roth RA. Protein kinase C modulates the insulin-stimulated increase in Akt1 and Akt3 activity in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun.243, 509–513 (1998).
  • Danielsen AG, Liu F, Hosomi Y, Shii K, Roth RA. Activation of protein kinase c a inhibits signaling by members of the insulin receptor family. J. Biol.Chem.270, 21600–22605 (1995).
  • Rajasekar P, Ravichandran MK, Anuradha CV. Intraperitoneal L-carnitine regulates lipid metabolism and reduces oxidative stress in fructose-induced hyperlipidaemic rats. Diabetologia Croatica34, 87–95(2006).
  • McGarry JD. Banting lecture 2001. Dysregulation of fatty acid metabolism in the etiology of Type 2 diabetes. Diabetes51, 7–18 (2002).
  • Saha AK, Schwarsin AJ, Rodiut R et al. Acitvation of malonyl CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside. J. Biol. Chem.275, 24279–24283 (2000).
  • Stefanovic-Racic M, Perdomo1 G, Mantell BS et al. A moderate increase in carnitine palmitoyltransferase-1a activity is sufficient to substantially reduce hepatic triglyceride levels. Am. J. Physiol. Endocrinol. Metab.294, E969–E977 (2008).
  • Rajasekar P, Viswanathan P, Anuradha CV. Beneficial impact of L-carnitine in liver: a study in a rat model of syndrome X. Amino Acids35(2), 475–483 (2007).
  • Rajasekar P, Anuradha CV. Fructose-induced hepatic gluconeogenesis: effect of L-carnitine. Life Sci.80, 1176–1183 (2007).
  • Mayes PA. Intermediary metabolism of fructose. Am. J. Clin. Nutr.58, 754S–765S (1993).
  • Gschwendt M, Kittstein W, Marks F. Protein kinase C activation by phorbol esters: do cysteine-rich regions and pseudosubstrate motifs play a role? Trends Biochem. Sci.16, 167–169 (1991).
  • McClung JP, Roneker CA, Mu W et al. Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase. Proc. Natl Acad. Sci. USA101, 8852–8857 (2004).
  • Chen H, Wertheimer SJ, Lin CH et al. Protein tyrosine phosphatases PTP1B and Syp are modulators of insulin-stimulated translocation of GLUT4 in transfected rat adipose cells. J. Biol. Chem.272, 8026–8031 (1997).
  • Ernsberger P, Johnson JL, Rosenthal T, Mirelman D, Koletsky RJ. Therapeutic actions of allylmercaptocaptopril and captopril in a rat model of metabolic syndrome. Am. J. Hypertens.20, 866–874 (2007).
  • Chong T, Naples M, Federico L et al. Effect of rosuvastatin on hepatic production of apolipoprotein B-containing lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia. Atherosclerosis185, 21–31 (2006).
  • Fiévet C, Fruchart JC, Staels B. PPAR α and PPAR γ dual agonists for the treatment of Type 2 diabetes and the metabolic syndrome. Curr. Opin. Pharmacol.6, 606–614 (2006).
  • Hardie DG. Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease. FEBS Lett.582, 81–89 (2008).
  • Rajasekar P, Anuradha CV. L-carnitine inhibits protein glycation in vitro and in vivo: evidence for a role in diabetic management. Acta Diabetologia44, 83–90 (2007).
  • Rajasekar P, Palanisamy N, Anuradha CV. Increase in nitric oxide and reductions in blood pressure, protein kinase C β II and oxidative stress by L-carnitine: a study in the fructose-fed hypertensive rat. Clin. Exp. Hypertens.29, 517–530 (2007).
  • Power RA, Hulver MW, Zhang JY et al. Carnitine revisited: potential use as adjunctive treatment in diabetes. Diabetologia50, 824–832 (2007).
  • Hathcock JN, Shao A. Risk assessment for carnitine. Regul. Toxicol. Pharmacol.46, 23–28 (2006).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.