The Association of Acetyl-l-Carnitine and Nicotinamide Remits the Experimental Diabetes in Mice by Multiple Low-dose Streptozotocin

Cresto, Juan C.; Bruno, L; Cao, Gabriel; Pastorale, Claudia; Confalonieri, Nicolas; Camberos, María del Carmen; Basabe, J. C.

doi:10.1097/01.mpa.0000236740.07854.b1

Cited by 13 publications

(13 citation statements)

References 25 publications

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“…The first reason was that it had been reported that children and adolescents with overt T1D showed low levels of free carnitine in the blood, although circulating levels of acyl-carnitines were high. 7, 8 Comparable data were obtained in experimental models 16, 17, 18 . However, we found that, at birth, our cohort of future T1D patients had significant low levels not only of free carnitine, but also of some acyl-carnitines.…”

Section: Discussionmentioning

confidence: 77%

Children who develop type 1 diabetes early in life show low levels of carnitine and amino acids at birth: does this finding shed light on the etiopathogenesis of the disease?

et al. 2013

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Background:Children and adolescents with overt type 1 diabetes (T1D) have been found to show an altered carnitine profile. This pattern has not previously been analyzed in neonates before onset of the disease.Materials and methods:Fifty children who developed T1D during the first 6 years of life, born and living in the Tuscany and Umbria Regions of Italy, were identified and 200 controls were recruited into the study. All newborns were subjected to extended neonatal screening by mass spectrometry at 48–72 h of life. Four controls for each of the 50 index cases were taken randomly and blinded in the same analytical batch. The panel used for neonatal screening consists of 13 amino acids, free carnitine, 33 acyl-carnitines and 21 ratios. All Guthrie cards are analyzed within 2 days of collection.Results:Total and free carnitine were found to be significantly lower in neonates who later developed T1D compared with controls. Moreover, the concentrations of the acyl-carnitines – acetyl-L-carnitine (C2), proprionylcarnitine (C3), 3-hydroxyisovalerylcarnitine (C5OH), miristoylcarnitine (C4), palmitoylcarnitine (C16) and stearoylcarnitine (C18) – were also significantly low in the cases vs controls. Furthermore, total amino-acid concentrations, expressed as the algebraic sum of all amino acids tested, showed a trend toward lower levels in cases vs controls.Conclusions:We found that carnitine and amino-acid deficit may be evident before the clinical appearance of T1D, possibly from birth. The evaluation of these metabolites in the neonatal period of children human leukocyte antigen genetically at ‘risk' to develop T1D, could represent an additional tool for the prediction of T1D and could also offer the possibility to design new strategies for the primary prevention of the disease from birth.

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Section: Discussionmentioning

confidence: 77%

Children who develop type 1 diabetes early in life show low levels of carnitine and amino acids at birth: does this finding shed light on the etiopathogenesis of the disease?

et al. 2013

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“…The combined treatment was studied in male C57BL/6J inbred mice, after inducing autoimmune diabetes with the injection of multiples low doses of streptozotocin. A prolonged treatment with 50 mg/Kg of acetyl-L-carnitine and 25 mg/Kg of nicotinamide resolved the immune diabetes induced in mice [82]. The associated treatment normalized the glucose levels, plasma insulin and normalized the ß-cell mass.…”

Section: Studies Supporting the Proposed Treatmentmentioning

confidence: 92%

“…We observed (Figure 1) that "diabetic splenocytes" decreased the insulin secretion from normal ß-cells stimulated with 16.5 mmol/L of glucose plus 5.5 mmol/L of theophylline; and 200 µg/well of L-carnitine can overcome this inhibition. The inhibition was probably due to cytokines released [82][83][84].…”

Section: Studies Supporting the Proposed Treatmentmentioning

confidence: 96%

“…The limit of insulin secretion under stimulation of 16.5 mmol/L glucose plus 5.5 mmol/L theophylline was more than 25 μU insulin/5000 dispersed islets cells in 5 min. Below this value it was assumed as "immune aggression" [82]. This potential risk was increased if the siblings had the genetic predisposition (specially the alleles DQB1*0302/*0201 of high susceptibility) which increased the possibility of developing autoantibodies.…”

Section: Figurementioning

confidence: 99%

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Acetyl-L-Carnitine and Nicotinamide for Prevention of Type 1 Diabetes. I-Literature Review which Gave Support to the Treatment. II-Case Report, Evaluation of Five Years Treatment

Tonietti¹

2015

Immunome Res

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“…Potentially relevant to diabetic patients with renal failure, nicotinamide also has been shown to reduce intestinal absorption of phosphate and prevent the development of hyperphosphatemia and progressive renal dysfunction [81]. In animal and cell culture studies, nicotinamide also can maintain normal fasting blood glucose in animals with streptozotocin-induced diabetes [82,83], reduce peripheral nerve injury during elevated glucose [84], lead to the remission of type 1 DM in mice with acetyl-l-carnitine [85], and can inhibit oxidative stress pathways that lead to apoptosis [63, [86][87][88][89].…”

Section: Innovative Strategies For Neurovascular Protection During Dmmentioning

confidence: 99%

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

Maiese

2008

Biomedicine & Pharmacotherapy

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SummaryOxidative stress is a principal pathway for the dysfunction and ultimate destruction of cells in the neuronal and vascular systems for several disease entities, non promoting the ravages of oxidative stress to any less of a degree than diabetes mellitus. Diabetes mellitus is increasing in incidence as a result of changes in human behavior that relate to diet and daily exercise and is predicted to affect almost 400 million individuals worldwide in another two decades. Furthermore, both type 1 and type 2 diabetes mellitus can lead to significant disability in the nervous and cardiovascular systems, such as cognitive loss and cardiac insufficiency. As a result, innovative strategies that directly target oxidative stress to preserve neuronal and vascular longevity could offer viable therapeutic options to diabetic patients in addition to more conventional treatments that are designed to control serum glucose levels. Here we discuss the novel application of nicotinamide, Wnt signaling, and erythropoietin that modulate cellular oxidative stress and offer significant promise for the prevention of diabetic complications in the nervous and vascular systems. Essential to this process is the precise focus upon diverse as well as common cellular pathways governed by nicotinamide, Wnt signaling, and erythropoietin to outline not only the potential benefits, but also the challenges and possible detriments of these therapies. In this way, new avenues of investigation can hopefully bypass toxic complications, or at the very least, avoid contraindications that may limit care and offer both safe and robust clinical treatment for patients.

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The Association of Acetyl-l-Carnitine and Nicotinamide Remits the Experimental Diabetes in Mice by Multiple Low-dose Streptozotocin

Abstract: The treatment with AC + N induced remission of autoimmune type 1 diabetes in mice produced by multiple low doses of streptozotocin.

Cited by 13 publications

References 25 publications

Children who develop type 1 diabetes early in life show low levels of carnitine and amino acids at birth: does this finding shed light on the etiopathogenesis of the disease?

Children who develop type 1 diabetes early in life show low levels of carnitine and amino acids at birth: does this finding shed light on the etiopathogenesis of the disease?

Acetyl-L-Carnitine and Nicotinamide for Prevention of Type 1 Diabetes. I-Literature Review which Gave Support to the Treatment. II-Case Report, Evaluation of Five Years Treatment

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

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