Establishment of New Highly Insulin-Sensitive Cell Lines and Screening of Compounds to Facilitate Glucose Consumption

To obtain compounds that promote glucose uptake in muscle cells, the novel cell lines A31-IS derived from Balb/c 3T3 A31 and C2C12-IS from mouse myoblast C2C12 were established. In both cell lines, glucose consumption was induced by insulin and suppressed by the addition of Akt-activating kinase inh...

Full description

Bibliographic Details
Main Authors: Kenji Hayata, Katsuichi Sakano, Shigeyuki Nishinaka
Format: Article
Language:English
Published: Elsevier 2008-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319313428
id doaj-6bbdc3f991ad44d682e2d4fa2aa89af2
record_format Article
spelling doaj-6bbdc3f991ad44d682e2d4fa2aa89af22020-11-25T01:07:36ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-011083348354Establishment of New Highly Insulin-Sensitive Cell Lines and Screening of Compounds to Facilitate Glucose ConsumptionKenji Hayata0Katsuichi Sakano1Shigeyuki Nishinaka2R&D Division, Exploratory Research Laboratories II, 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan; Correspondence author. hayata.kenji.v6@daiichisankyo.co.jpR&D Division, Exploratory Research Laboratories I, Daiichi-Sankyo Co., Ltd., 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, JapanR&D Division, Exploratory Research Laboratories II, 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, JapanTo obtain compounds that promote glucose uptake in muscle cells, the novel cell lines A31-IS derived from Balb/c 3T3 A31 and C2C12-IS from mouse myoblast C2C12 were established. In both cell lines, glucose consumption was induced by insulin and suppressed by the addition of Akt-activating kinase inhibitor. The A31-IS cells highly express the insulin receptor β chains, Glut4, and uncoupling protein-3, as compared to the parent Balb /c 3T3 A31 cells, and C2C12-IS cells highly express the insulin receptor β chain as compared to its parent cell line. Using A31-IS cells, we screened our library compounds and obtained three compounds, DF-4394, DF-4451, and DG-5451. These compounds dose-dependently promoted glucose consumption in A31-IS cells and facilitated [3H]-2-deoxyglucose uptake in differentiated C2C12-IS cells. The compounds that we obtained from the library screening will be good candidates for improving insulin resistance in muscle cells. Keywords:: skeletal muscle cell, insulin, glucose uptakehttp://www.sciencedirect.com/science/article/pii/S1347861319313428
collection DOAJ
language English
format Article
sources DOAJ
author Kenji Hayata
Katsuichi Sakano
Shigeyuki Nishinaka
spellingShingle Kenji Hayata
Katsuichi Sakano
Shigeyuki Nishinaka
Establishment of New Highly Insulin-Sensitive Cell Lines and Screening of Compounds to Facilitate Glucose Consumption
Journal of Pharmacological Sciences
author_facet Kenji Hayata
Katsuichi Sakano
Shigeyuki Nishinaka
author_sort Kenji Hayata
title Establishment of New Highly Insulin-Sensitive Cell Lines and Screening of Compounds to Facilitate Glucose Consumption
title_short Establishment of New Highly Insulin-Sensitive Cell Lines and Screening of Compounds to Facilitate Glucose Consumption
title_full Establishment of New Highly Insulin-Sensitive Cell Lines and Screening of Compounds to Facilitate Glucose Consumption
title_fullStr Establishment of New Highly Insulin-Sensitive Cell Lines and Screening of Compounds to Facilitate Glucose Consumption
title_full_unstemmed Establishment of New Highly Insulin-Sensitive Cell Lines and Screening of Compounds to Facilitate Glucose Consumption
title_sort establishment of new highly insulin-sensitive cell lines and screening of compounds to facilitate glucose consumption
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2008-01-01
description To obtain compounds that promote glucose uptake in muscle cells, the novel cell lines A31-IS derived from Balb/c 3T3 A31 and C2C12-IS from mouse myoblast C2C12 were established. In both cell lines, glucose consumption was induced by insulin and suppressed by the addition of Akt-activating kinase inhibitor. The A31-IS cells highly express the insulin receptor β chains, Glut4, and uncoupling protein-3, as compared to the parent Balb /c 3T3 A31 cells, and C2C12-IS cells highly express the insulin receptor β chain as compared to its parent cell line. Using A31-IS cells, we screened our library compounds and obtained three compounds, DF-4394, DF-4451, and DG-5451. These compounds dose-dependently promoted glucose consumption in A31-IS cells and facilitated [3H]-2-deoxyglucose uptake in differentiated C2C12-IS cells. The compounds that we obtained from the library screening will be good candidates for improving insulin resistance in muscle cells. Keywords:: skeletal muscle cell, insulin, glucose uptake
url http://www.sciencedirect.com/science/article/pii/S1347861319313428
work_keys_str_mv AT kenjihayata establishmentofnewhighlyinsulinsensitivecelllinesandscreeningofcompoundstofacilitateglucoseconsumption
AT katsuichisakano establishmentofnewhighlyinsulinsensitivecelllinesandscreeningofcompoundstofacilitateglucoseconsumption
AT shigeyukinishinaka establishmentofnewhighlyinsulinsensitivecelllinesandscreeningofcompoundstofacilitateglucoseconsumption
_version_ 1725186570081796096