Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice

Svetlana E Nikoulina1, Dietmar Fuchs2, Phillip Moheno11SanRx Pharmaceuticals, Inc, La Jolla, CA, USA; 2Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, AustriaAbstract: Calcium pterins have been shown to be significant immunotherapeutic agents in models of breast...

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Autores principales:	Fuchs D, Nikoulina SE, Moheno P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/8a1efcd4dc8c4f15886ee1c6458b8f7d
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spelling	oai:doaj.org-article:8a1efcd4dc8c4f15886ee1c6458b8f7d2021-12-02T09:03:43ZEffect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice1178-7007https://doaj.org/article/8a1efcd4dc8c4f15886ee1c6458b8f7d2012-02-01T00:00:00Zhttp://www.dovepress.com/effect-of-orally-administered-dipterinyl-calcium-pentahydrate-on-oral--a9341https://doaj.org/toc/1178-7007Svetlana E Nikoulina1, Dietmar Fuchs2, Phillip Moheno11SanRx Pharmaceuticals, Inc, La Jolla, CA, USA; 2Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, AustriaAbstract: Calcium pterins have been shown to be significant immunotherapeutic agents in models of breast cancer, hepatitis B, and tuberculosis (Bacillus Calmette-Gu&eacute;rin mycobacteria). These compunds modulate the immuno-enzyme indoleamine 2,3-dioxygenase (IDO) and the blood levels of several identified inflammatory cytokines. Recent research into the pathology of diabetes implicates inflammatory factors in the progression of the disease, leading the authors to study its possible control by one of the calcium pterins, dipterinyl calcium pentahydrate (DCP).The investigators tested DCP as a novel therapeutic for type 2 diabetes. Female C57BL/6 J mice with diet-induced obesity were fed a high-fat diet and were administered DCP in 0.4% carboxymethylcellulose for 21 days. Blood glucose was followed during the dosing period, and an oral glucose tolerance test (OGTT) was carried out on day 21. Measurements of plasma indoleamine 2,3-dioxygenase metabolites (tryptophan and kynurenine) and certain cytokines and chemokines were also taken. DCP 7 mg/kg/day reduced OGTT area under the curve (OGTT/AUC) by 50% (P &lt; 0.05). A significant multivariate regression (P = 0.013; R2 = 0.571) of OGTT/AUC was derived from DCP dosage and plasma Trp. Elevated plasma Trp concentration, likely from heterogeneity in diet and/or indoleamine 2,3-dioxygenase activity, was found to correlate with higher OGTT/AUC diabetic measures, possibly via inhibition of histamine degradation. In conclusion, an optimum dose of DCP 7 mg/kg/day significantly improved the OGTT diabetic state in these female diet-induced obese mice.Keywords: diabetes, immunotherapy, oral glucose tolerance test, tryptophan, kynurenineFuchs DNikoulina SEMoheno PDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2012, Iss default, Pp 43-47 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Fuchs D Nikoulina SE Moheno P Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice
description	Svetlana E Nikoulina1, Dietmar Fuchs2, Phillip Moheno11SanRx Pharmaceuticals, Inc, La Jolla, CA, USA; 2Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, AustriaAbstract: Calcium pterins have been shown to be significant immunotherapeutic agents in models of breast cancer, hepatitis B, and tuberculosis (Bacillus Calmette-Gu&eacute;rin mycobacteria). These compunds modulate the immuno-enzyme indoleamine 2,3-dioxygenase (IDO) and the blood levels of several identified inflammatory cytokines. Recent research into the pathology of diabetes implicates inflammatory factors in the progression of the disease, leading the authors to study its possible control by one of the calcium pterins, dipterinyl calcium pentahydrate (DCP).The investigators tested DCP as a novel therapeutic for type 2 diabetes. Female C57BL/6 J mice with diet-induced obesity were fed a high-fat diet and were administered DCP in 0.4% carboxymethylcellulose for 21 days. Blood glucose was followed during the dosing period, and an oral glucose tolerance test (OGTT) was carried out on day 21. Measurements of plasma indoleamine 2,3-dioxygenase metabolites (tryptophan and kynurenine) and certain cytokines and chemokines were also taken. DCP 7 mg/kg/day reduced OGTT area under the curve (OGTT/AUC) by 50% (P &lt; 0.05). A significant multivariate regression (P = 0.013; R2 = 0.571) of OGTT/AUC was derived from DCP dosage and plasma Trp. Elevated plasma Trp concentration, likely from heterogeneity in diet and/or indoleamine 2,3-dioxygenase activity, was found to correlate with higher OGTT/AUC diabetic measures, possibly via inhibition of histamine degradation. In conclusion, an optimum dose of DCP 7 mg/kg/day significantly improved the OGTT diabetic state in these female diet-induced obese mice.Keywords: diabetes, immunotherapy, oral glucose tolerance test, tryptophan, kynurenine
format	article
author	Fuchs D Nikoulina SE Moheno P
author_facet	Fuchs D Nikoulina SE Moheno P
author_sort	Fuchs D
title	Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice
title_short	Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice
title_full	Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice
title_fullStr	Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice
title_full_unstemmed	Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice
title_sort	effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/8a1efcd4dc8c4f15886ee1c6458b8f7d
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Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice

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