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Mingrone Geltrude - One of the best experts on this subject based on the ideXlab platform.
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Use of dicarboxylic Acids in type 2 diabetes
'Wiley', 2013Co-Authors: Mingrone Geltrude, Castagneto-gissey Lidia, Macé KatherineAbstract:Even-number, medium-chain dicarboxylic Acids (DAs), naturally occurring in higher plants, are a promising alternative energy substrate. Unlike the homologous fatty Acids, DAs are soluble in water as salts. They are β-oxidized, providing acetyl-CoA and succinyl-CoA, the latter being an intermediate of the tricarboxylic Acid cycle. Sebacic Acid and Dodecanedioic Acid, DAs with 10 and 12 carbon atoms respectively, provide 6.6 and 7.2 kcal g⁻¹ each; therefore, their energy density is intermediate between glucose and fatty Acids. Dicarboxylic Acids have been proved to be safe in both experimental animals and humans, and their use has recently been proposed in diabetes. Studies in animals and humans with type 2 diabetes showed that oral administration of sebacic Acid improved glycaemic control, probably by enhancing insulin sensitivity, and reduced hepatic gluconeogenesis and glucose output. Moreover, Dodecanedioic Acid intake reduced muscle fatigue during exercise in subjects with type 2 diabetes, suggesting an improvement of energy utilization and 'metabolic flexibility'. In this article, we review the natural sources of DAs, their fate in animals and humans and their effect in improving glucose metabolism in type 2 diabetes
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Use of Dicarboxylic Acids in Type 2 Diabetes
'Wiley', 2012Co-Authors: Mingrone Geltrude, Castagneto Gissey L, Mac\ue9 K.Abstract:Even number, medium chain dicarboxylic Acids (DAs), naturally occurring in high plants, are a promising alternative energy substrate. Contrary to the homologous fatty Acids, DAs are soluble in water as salts. They are \u3b2-oxidized providing Acetyl-CoAs and Succinyl-CoA, this latter an intermediate of the tricarboxylic Acid cycle. Sebacic Acid and Dodecanedioic Acid, DAs with 10 and 12 carbon atoms respectively, provide 6.6 kcal/g and 7.2 kcal/g each; therefore, their energy density is intermediate between glucose and fatty Acids. DAs have been proved to be safe in both experimental animal and humans and their use has been recently proposed in diabetes. Studies in animals and humans with type 2 diabetes showed that oral administration of sebacic Acid improved glycaemic control, probably by enhancing insulin sensitivity, and reduced hepatic gluconeogenesis and glucose output. Moreover, Dodecanedioic Acid intake reduced muscle fatigue during exercise in type-2 diabetes subjects, suggesting an improvement of energy utilization and "metabolic flexibility". In this article we will review the natural sources of DAs, their fate in animals and humans and their effect in improving glucose metabolism in type 2 diabetes. \ua9 2012 The Authors. British Journal of Clinical Pharmacology \ua9 2012 The British Pharmacological Society
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Approximate linear confidence and curvature of a kinetic model of Dodecanedioic Acid in humans
country:USA, 2005Co-Authors: Panunzi Simona, De Gaetano Andrea, Mingrone GeltrudeAbstract:Dicarboxylic Acids with an even number of carbon atoms have been proposed as an alternate energy substrate for enteral or parenteral nutrition in the acutely ill patient, due to their water solubility and their yielding TCA cycle intermediates upon beta-oxidation. In the present work, a nonlinear compartmental model of the kinetics of Dodecanedioic Acid is developed, and its parameters are estimated from time concentration experimental observations obtained from six healthy volunteers undergoing a per os administration of 3 g of the substance. Although the model is linear in the transfer of the free substance from plasma to the tissues, the exchange between gut and plasma compartments is represented as a saturable function. Albumin binding is then incorporated to obtain the final model in terms of the measured total concentrations. Estimates of the model's structural parameters were computed for each experimental subject, and the usual single-subject approximate confidence regions for the parameters were derived by inversion of the Hessian at the optimum. To verify the applicability of this approximation, the nonlinearity of the expectation surface at the optimum was measured by computing the normal (intrinsic) component of curvature. Because the model curvature was excessive in all subjects, the usual approximation could not be trusted to provide acceptable approximations to the parameter confidence regions. A suitable Monte Carlo simulation yielded empirical joint parameter distributions from which the approximate parameter variances could finally be obtaine
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Oxidation of D-[U-(14)C] glucose and [1,12-(14)C] Dodecanedioic Acid by pancreatic islets from Goto-Kakizaki rats.
'Georg Thieme Verlag KG', 2001Co-Authors: Malaisse Willy, Mingrone Geltrude, Doherty Margaret, Ladrière Laurence, Greco AlessandroAbstract:In pancreatic islets from hereditarily diabetic GK rats, [1,12 -(14)C] Dodecanedioic Acid (5.0 mM) was oxidized at a rate representing about 5 % of that of D-[U - (14)C] glucose (8.3 mM). Dioic Acid and hexose failed to exert any significant reciprocal effects on their respective oxidation. The production of (14)CO(2) from [1,12 -(14)C] Dodecanedioic Acid was proportional to its concentration in the 0.2 - 5.0 mM range. These results were essentially comparable to those obtained in islets from control rats. They extend, therefore, to GK rats the knowledge that Dodecanedioic Acid acts as a nutrient in pancreatic islet cells.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe
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Oxidation of [1,12-14C]Dodecanedioic Acid by rat pancreatic islets
2000Co-Authors: Wj Malaisse, Av Greco, Mingrone GeltrudeAbstract:Several aliphatic dioic Acids were recently reported to stimulate insulin release in isolated rat pancreatic islets incubated at close-to-physiological D-glucose concentrations. In order to gain insight into the mode of action of these Acids in pancreatic islet B-cells, the oxidation of [1,12-14C]Dodecanedioic Acid (5.0 mM) was now measured in rat islets. Expressed as pmol of [1, 12-14C]Dodecanedioic Acid equivalent, the production of 14CO2 was close to 1.0 pmol/islet per 120 min, representing about 8% of that attributable to the oxidation of D-[U-14C]-glucose (8.3 mM). The dioic Acid and the hexose failed to exert any significant reciprocal effect upon their respective oxidation rate. These findings support the view that the insulinotropic action of Dodecanedioic Acid, and presumably other aliphatic dioic Acids, is causally linked to their capacity to act as nutrients in pancreatic islet cells
Cornelis Jakobs - One of the best experts on this subject based on the ideXlab platform.
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novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase i deficiency
Molecular Genetics and Metabolism, 2005Co-Authors: Stanley H Korman, Hans R. Waterham, Alisa Gutman, Cornelis JakobsAbstract:Abstract Detection of hepatic carnitine palmitoyltransferase I (CPT IA) deficiency by metabolite screening may be problematic. The urine organic Acid profile is generally said to be normal and no abnormal or increased acylcarnitine species are evident on bloodspot tandem MS examination. We diagnosed CPT IA deficiency presenting with acute encephalopathy +/− hypoglycemia and hepatomegaly in one Bukharan Jewish and two Palestinian Arab infants from consanguineous families. CPT1A mutation analysis identified two novel nonsense mutations, c.1737C > A (Y579X) and c.1600delC (L534fsX), extending the known genetic heterogeneity in this disorder. A distinctive organic Aciduria was observed in all three patients, even several days after initiation of treatment and resolution of symptoms. Abnormal findings included a hypoketotic dicarboxylic Aciduria with prominence of the C 12 dicarboxylic (Dodecanedioic) Acid. This C 12 dicarboxylic Aciduria suggests that CPT I may play a role in uptake of long-chain dicarboxylic Acids by mitochondria after their initial shortening by β-oxidation in peroxisomes. In addition, increased excretion of 3-hydroxyglutaric Acid was detected in all three patients, a finding previously observed only in glutaric Aciduria type 1, ketosis, and short-chain hydroxyacyl-CoA dehydrogenase deficiency. Examination of urine organic Acids with awareness of these metabolic findings may lead to improved diagnosis of this seemingly rare disorder.
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Novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase I deficiency
Molecular Genetics and Metabolism, 2005Co-Authors: Stanley H Korman, Hans R. Waterham, Alisa Gutman, Cornelis JakobsAbstract:Detection of hepatic carnitine palmitoyltransferase I (CPT IA) deficiency by metabolite screening may be problematic. The urine organic Acid profile is generally said to be normal and no abnormal or increased acylcarnitine species are evident on bloodspot tandem MS examination. We diagnosed CPT IA deficiency presenting with acute encephalopathy +/- hypoglycemia and hepatomegaly in one Bukharan Jewish and two Palestinian Arab infants from consanguineous families. CPT1A mutation analysis identified two novel nonsense mutations, c.1737C>A (Y579X) and c.1600delC (L534fsX), extending the known genetic heterogeneity in this disorder. A distinctive organic Aciduria was observed in all three patients, even several days after initiation of treatment and resolution of symptoms. Abnormal findings included a hypoketotic dicarboxylic Aciduria with prominence of the C12 dicarboxylic (Dodecanedioic) Acid. This C12 dicarboxylic Aciduria suggests that CPT I may play a role in uptake of long-chain dicarboxylic Acids by mitochondria after their initial shortening by beta-oxidation in peroxisomes. In addition, increased excretion of 3-hydroxyglutaric Acid was detected in all three patients, a finding previously observed only in glutaric Aciduria type 1, ketosis, and short-chain hydroxyacyl-CoA dehydrogenase deficiency. Examination of urine organic Acids with awareness of these metabolic findings may lead to improved diagnosis of this seemingly rare disorder.
Kaushik Chatterjee - One of the best experts on this subject based on the ideXlab platform.
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biodegradable galactitol based crosslinked polyesters for controlled release and bone tissue engineering
Materials Science and Engineering: C, 2017Co-Authors: Janeni Natarajan, Sahitya Movva, Giridhar Madras, Kaushik ChatterjeeAbstract:Various classes of biodegradable polymers have been explored towards finding alternates for the existing treatments for bone disorders. In this framework, two families of polyesters using an array of crosslinkers were synthesized. One was based on galactiol/adipic Acid and the other based on galactitol/Dodecanedioic Acid. The structures of the polymers were confirmed by FTIR and further confirmed by H-1 NMR. DSC showed that the polymers were amorphous and the glass transition temperature increased with increase in crosslinking. DMA and contact angle analysis revealed that the modulus and hydrophobicity increased with increase in crosslinking. Swelling studies demonstrated that %swelling decreased with increase in crosslinlcing. The in vitro hydrolytic degradation studies and dye release studies of all the polymers exhibited that the degradation and release rate decreased with increase in crosslinking, hydrophobicity and modulus. Degradation and release followed first order kinetics and Higuchi kinetics, respectively. The preliminary in vitro cytotoxicity studies proved that this array of polymers was not cytotoxic. Osteogenic differentiation of pre-osteoblasts was observed in three dimensional (3D) porous scaffolds prepared using these polymers. This study demonstrates the ability to modulate the physical properties, degradation and release kinetics of these biodegradable polymers through smart selection of crosslinkers. The findings of these studies have important implications for developing novel biodegradable polymers for drug delivery and tissue engineering applications. (C) 2017 Elsevier B.V.All rights reserved.
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localized delivery and enhanced osteogenic differentiation with biodegradable galactitol polyester elastomers
RSC Advances, 2016Co-Authors: Janeni Natarajan, Giridhar Madras, Kaushik ChatterjeeAbstract:Given that a large fraction of the population suffers from orthopaedic diseases, the research in developing polymeric biomaterials for bone tissue regeneration applications is witnessing an exponential growth rate. We present a spectrum of novel polyesters synthesized by the reaction of galactitol with dicarboxylic Acids, namely adipic Acid, suberic Acid and Dodecanedioic Acid. Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy confirmed the chemical structure of the polymers. Thermal characterization revealed that these polyesters were semi-crystalline. The molecular weight of the polyesters showed an increase with increase in the chain length of the diAcid and the molar ratio of galactitol : diAcid. Dynamic mechanical analysis showed that the polymers were elastomeric in nature with the increase in chain length and molar ratio of galactitol : diAcids. Surface hydrophobicity and the swelling ratio increase with increase in the chain length and molar ratio of galactitol : diAcids. Hydrolytic degradation studies demonstrated that the kinetics of the degradation followed first order. Dye release studies indicated that the rate of release followed Higuchi kinetics. In vitro studies confirmed the cytocompatible nature of these polymers. Mineralization by osteoblasts in vitro suggests that these polymers support osteogenic differentiation, thus elucidating that these polymers are promising candidate materials for bone tissue engineering. Thus, this study presents a significant advance in which the mechanical properties, degradation and release rates of the polyesters may be tuned by manipulating the process parameters.
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maltitol based biodegradable polyesters with tailored degradation and controlled release for bone regeneration
RSC Advances, 2016Co-Authors: Janeni Natarajan, Giridhar Madras, Kaushik ChatterjeeAbstract:Despite extensive research performed in the area of drug delivery and tissue engineering, the search for a perfect biomaterial remains an ongoing process. In an effort to find this material, novel maltitol-based polyesters using three different dicarboxylic Acids (DCAs; adipic Acid, Dodecanedioic Acid and suberic Acid) were synthesized and their properties were investigated. The chemical structure of the polymers was confirmed using Fourier transform infrared and proton nuclear magnetic resonance spectroscopies. Thermal characterization revealed that the polymers were amorphous and that the glass transition temperature decreased with an increase in the chain length and molar ratio of maltitol : DCAs. Mechanical studies showed that the moduli of these polymers were comparable to those of the components of the skeletal system. Contact angle goniometry confirmed that the hydrophobicity of the polymers increased with increase in chain length and the molar ratio of maltitol : DCAs. The polymer degradation followed first order kinetics whereas dye release from these polymers followed zero order kinetics. Both the degradation and dye release studies demonstrated that the degradation and release decreased with increase in chain length and molar ratio of maltitol : DCA. The degradation and dye release can be modulated based on the chain length and the molar ratio of Acids. Preliminary cytocompatibility studies showed that these polymers were cytocompatible. Mineralization studies revealed that these polymers showed increased mineralization when compared to results obtained with controls. Thus, this family of polyesters can serve as effective biomaterials for bone tissue engineering with tunable degradation and controlled release properties.
Stanley H Korman - One of the best experts on this subject based on the ideXlab platform.
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novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase i deficiency
Molecular Genetics and Metabolism, 2005Co-Authors: Stanley H Korman, Hans R. Waterham, Alisa Gutman, Cornelis JakobsAbstract:Abstract Detection of hepatic carnitine palmitoyltransferase I (CPT IA) deficiency by metabolite screening may be problematic. The urine organic Acid profile is generally said to be normal and no abnormal or increased acylcarnitine species are evident on bloodspot tandem MS examination. We diagnosed CPT IA deficiency presenting with acute encephalopathy +/− hypoglycemia and hepatomegaly in one Bukharan Jewish and two Palestinian Arab infants from consanguineous families. CPT1A mutation analysis identified two novel nonsense mutations, c.1737C > A (Y579X) and c.1600delC (L534fsX), extending the known genetic heterogeneity in this disorder. A distinctive organic Aciduria was observed in all three patients, even several days after initiation of treatment and resolution of symptoms. Abnormal findings included a hypoketotic dicarboxylic Aciduria with prominence of the C 12 dicarboxylic (Dodecanedioic) Acid. This C 12 dicarboxylic Aciduria suggests that CPT I may play a role in uptake of long-chain dicarboxylic Acids by mitochondria after their initial shortening by β-oxidation in peroxisomes. In addition, increased excretion of 3-hydroxyglutaric Acid was detected in all three patients, a finding previously observed only in glutaric Aciduria type 1, ketosis, and short-chain hydroxyacyl-CoA dehydrogenase deficiency. Examination of urine organic Acids with awareness of these metabolic findings may lead to improved diagnosis of this seemingly rare disorder.
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Novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase I deficiency
Molecular Genetics and Metabolism, 2005Co-Authors: Stanley H Korman, Hans R. Waterham, Alisa Gutman, Cornelis JakobsAbstract:Detection of hepatic carnitine palmitoyltransferase I (CPT IA) deficiency by metabolite screening may be problematic. The urine organic Acid profile is generally said to be normal and no abnormal or increased acylcarnitine species are evident on bloodspot tandem MS examination. We diagnosed CPT IA deficiency presenting with acute encephalopathy +/- hypoglycemia and hepatomegaly in one Bukharan Jewish and two Palestinian Arab infants from consanguineous families. CPT1A mutation analysis identified two novel nonsense mutations, c.1737C>A (Y579X) and c.1600delC (L534fsX), extending the known genetic heterogeneity in this disorder. A distinctive organic Aciduria was observed in all three patients, even several days after initiation of treatment and resolution of symptoms. Abnormal findings included a hypoketotic dicarboxylic Aciduria with prominence of the C12 dicarboxylic (Dodecanedioic) Acid. This C12 dicarboxylic Aciduria suggests that CPT I may play a role in uptake of long-chain dicarboxylic Acids by mitochondria after their initial shortening by beta-oxidation in peroxisomes. In addition, increased excretion of 3-hydroxyglutaric Acid was detected in all three patients, a finding previously observed only in glutaric Aciduria type 1, ketosis, and short-chain hydroxyacyl-CoA dehydrogenase deficiency. Examination of urine organic Acids with awareness of these metabolic findings may lead to improved diagnosis of this seemingly rare disorder.
Yinhua Wan - One of the best experts on this subject based on the ideXlab platform.
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high level productivity of α ω Dodecanedioic Acid with a newly isolated candida viswanathii strain
Journal of Industrial Microbiology & Biotechnology, 2017Co-Authors: Weifeng Cao, Jianquan Luo, Junxiang Yin, Yinhua WanAbstract:α,ω-Dicarboxylic Acids (DC) are versatile chemical intermediates with different chain lengths, which are well-known as polymer building block. In this work, a new strain with high productivity of DC was isolated from oil-contaminated soil. Based on the morphology and phylogenetic analyses of the internal transcribed spacer sequences, it was characterized as Candida viswanathii. It was found that the contribution of carbon flux to the cell growth and DC production from n-dodecane could be regulated by the sucrose and yeast extract concentrations in the medium, and besides the broth pH, a suitable proportioning of sucrose and yeast extract was the key to achieve the optimal transition from cell growth phase to DC production phase. By optimizing culture conditions in a 7.5-L bioreactor, a higher DC productivity of 1.59 g·L−1 h−1 with a corresponding concentration of 181.6 g/L was obtained. After the purification of DC from the culture, the results from gas chromatography–mass spectrometry, infrared spectroscopy and 1H-NMR showed that α,ω-Dodecanedioic Acid (DC12) was the major product of C. viswanathii ipe-1 using pure n-dodecane as substrate. For the first time, we reported that a high productivity of DC12 could be produced by C. viswanathii.