Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose

Siddhartha Shankar Das, Hiroto Hayashi, Taiki Sato, Ren Yamada, Masahiro Hiratsuka, Noriyasu Hirasawa Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan Objective: Type 1 and 2 diabetes are characterize...

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Autores principales:	Das SS, Hayashi H, Sato T, Yamada R, Hiratsuka M, Hirasawa N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/eea5802a9134434587b41b69a54f9e36
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spelling	oai:doaj.org-article:eea5802a9134434587b41b69a54f9e362021-12-02T02:14:46ZRegulation of dipeptidyl peptidase 4 production in adipocytes by glucose1178-7007https://doaj.org/article/eea5802a9134434587b41b69a54f9e362014-05-01T00:00:00Zhttp://www.dovepress.com/regulation-of-dipeptidyl-peptidase-4-production-in-adipocytes-by-gluco-a16978https://doaj.org/toc/1178-7007 Siddhartha Shankar Das, Hiroto Hayashi, Taiki Sato, Ren Yamada, Masahiro Hiratsuka, Noriyasu Hirasawa Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan Objective: Type 1 and 2 diabetes are characterized by elevated blood glucose levels and increased dipeptidyl peptidase 4 (DPP4) activity levels in the serum. However, previous studies reported a negative correlation between glucose concentrations and DPP4 levels. The purpose of this study was to elucidate the connection between glucose and DPP4 in adipocytes under physiological and diabetic conditions, because DPP4 is an adipokine. Methods: Blood glucose and serum DPP4 levels were measured, and adipocytes were collected from mice under normal, high-fat diet fed, and diabetic conditions. The adipocytes obtained were incubated for 24 hours in medium containing 5.5 or 25 mM glucose, and 3T3-L1 preadipocytes were differentiated under 5.5 or 25 mM glucose. Adipocytes from mice and 3T3-L1 were stimulated by tumor necrosis factor-α (TNF-α) for 24 hours. The levels of released and intracellular DPP4 were determined by enzyme-linked immunosorbent assay. Results: Mice fed high-fat diet had lower serum DPP4 levels in the first and second week than controls. However, this difference gradually disappeared over 6 weeks. The differentiation of 3T3-L1 adipocytes under 25 mM glucose produced lower DPP4 levels than those differentiated under 5.5 mM; this was also observed in isolated adipocytes from mice. However, these effects of glucose were lost in adipocytes from diabetic mice, and an increase in total DPP4 levels was observed. The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration. Conclusion: The production of DPP4 in adipocytes was negatively regulated by 25 mM glucose under physiological conditions, but not in diabetic mice. Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release. Keywords: DPP4, 3T3-L1, diabetes, TNF-αDas SSHayashi HSato TYamada RHiratsuka MHirasawa NDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2014, Iss default, Pp 185-194 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Das SS Hayashi H Sato T Yamada R Hiratsuka M Hirasawa N Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose
description	Siddhartha Shankar Das, Hiroto Hayashi, Taiki Sato, Ren Yamada, Masahiro Hiratsuka, Noriyasu Hirasawa Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan Objective: Type 1 and 2 diabetes are characterized by elevated blood glucose levels and increased dipeptidyl peptidase 4 (DPP4) activity levels in the serum. However, previous studies reported a negative correlation between glucose concentrations and DPP4 levels. The purpose of this study was to elucidate the connection between glucose and DPP4 in adipocytes under physiological and diabetic conditions, because DPP4 is an adipokine. Methods: Blood glucose and serum DPP4 levels were measured, and adipocytes were collected from mice under normal, high-fat diet fed, and diabetic conditions. The adipocytes obtained were incubated for 24 hours in medium containing 5.5 or 25 mM glucose, and 3T3-L1 preadipocytes were differentiated under 5.5 or 25 mM glucose. Adipocytes from mice and 3T3-L1 were stimulated by tumor necrosis factor-α (TNF-α) for 24 hours. The levels of released and intracellular DPP4 were determined by enzyme-linked immunosorbent assay. Results: Mice fed high-fat diet had lower serum DPP4 levels in the first and second week than controls. However, this difference gradually disappeared over 6 weeks. The differentiation of 3T3-L1 adipocytes under 25 mM glucose produced lower DPP4 levels than those differentiated under 5.5 mM; this was also observed in isolated adipocytes from mice. However, these effects of glucose were lost in adipocytes from diabetic mice, and an increase in total DPP4 levels was observed. The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration. Conclusion: The production of DPP4 in adipocytes was negatively regulated by 25 mM glucose under physiological conditions, but not in diabetic mice. Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release. Keywords: DPP4, 3T3-L1, diabetes, TNF-α
format	article
author	Das SS Hayashi H Sato T Yamada R Hiratsuka M Hirasawa N
author_facet	Das SS Hayashi H Sato T Yamada R Hiratsuka M Hirasawa N
author_sort	Das SS
title	Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose
title_short	Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose
title_full	Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose
title_fullStr	Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose
title_full_unstemmed	Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose
title_sort	regulation of dipeptidyl peptidase 4 production in adipocytes by glucose
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/eea5802a9134434587b41b69a54f9e36
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Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose

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