Chronic Hyperglycemia, Independent of Plasma Lipid Levels, Is Sufficient for the Loss of β-Cell Differentiation and Secretory Function in the db/db Mouse Model of Diabetes

Chronic Hyperglycemia, Independent of Plasma Lipid Levels, Is Sufficient for the Loss of β-Cell Differentiation and Secretory Function in the db/db Mouse Model of Diabetes Cecilie Kjørholt , Mia C. Åkerfeldt , Trevor J. Biden and D. Ross Laybutt From the Diabetes and Obesity Research Program, Garvan...

Full description

Saved in:
Bibliographic Details
Published inDiabetes (New York, N.Y.) Vol. 54; no. 9; pp. 2755 - 2763
Main Authors KJØRHOLT, Cecilie, AKERFELDT, Mia C, BIDEN, Trevor J, LAYBUTT, D. Ross
Format Journal Article
LanguageEnglish
Published Alexandria, VA American Diabetes Association 01.09.2005
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Chronic Hyperglycemia, Independent of Plasma Lipid Levels, Is Sufficient for the Loss of β-Cell Differentiation and Secretory Function in the db/db Mouse Model of Diabetes Cecilie Kjørholt , Mia C. Åkerfeldt , Trevor J. Biden and D. Ross Laybutt From the Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent’s Hospital, Sydney, Australia Address correspondence and reprint requests to Ross Laybutt, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, Sydney 2010, Australia. E-mail: r.laybutt{at}garvan.org.au Abstract The β-cell is a highly specialized cell with a unique differentiation that optimizes glucose-induced insulin secretion (GIIS). Here, we evaluated changes in gene expression that accompany β-cell dysfunction in the db/db mouse model of type 2 diabetes. In db/db islets, mRNA levels of many genes implicated in β-cell glucose sensing were progressively reduced with time, as were several transcription factors important for the maintenance of β-cell differentiation. Conversely, genes normally suppressed in β-cells, such as a variety of stress response mediators and inhibitor of differentiation/DNA binding 1, a gene capable of inhibiting differentiation, were markedly increased. We assessed whether this global alteration in the pattern of β-cell gene expression was related more to chronic hyperglycemia or hyperlipidemia; db/db mice were treated with phlorizin, which selectively lowered plasma glucose, or bezafibrate, which selectively lowered plasma lipids. GIIS as well as the majority of the changes in gene expression were completely normalized by lowering glucose but were unaffected by lowering lipids. However, the restoration of GIIS was not accompanied by normalized uncoupling protein 2 or peroxisome proliferator–activated receptor γ mRNA levels, which were upregulated in db/db islets. These studies demonstrate that hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of β-cell differentiation and secretory function in db/db mice. ATF-3, activating transcription factor 3 Β2/NeuroD, β-cell E-box trans-activator 2 CPT-1, carnitine palmitoyl transferase 1 GIIS, glucose-induced insulin secretion HNF1α, hepatocyte nuclear factor 1α IAPP, islet amyloid polypeptide ID-1, inhibitor of differentiation/DNA binding 1 KRHB, Krebs-Ringer HEPES buffer mGPDH, mitochondrial glycerol phosphate dehydrogenase NEFA, nonesterified fatty acid PDX-1, pancreatic duodenal homeobox-1 PPAR, peroxisome proliferator–activated receptor SNAP25, synaptosomal-associated protein of 25 kDa UCP-2, uncoupling protein 2 Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted June 3, 2005. Received April 19, 2005. DIABETES
AbstractList The β-cell is a highly specialized cell with a unique differentiation that optimizes glucose-induced insulin secretion (GIIS). Here, we evaluated changes in gene expression that accompany β-cell dysfunction in the db/db mouse model of type 2 diabetes. In db/db islets, mRNA levels of many genes implicated in β-cell glucose sensing were progressively reduced with time, as were several transcription factors important for the maintenance of β-cell differentiation. Conversely, genes normally suppressed in β-cell, such as a variety of stress response mediators and inhibitor of differentiation/ DNA binding 1, a gene capable of inhibiting differentiation, were markedly increased. We assessed whether this global alteration in the pattern of β-cell gene expression was related more to chronic hyperglycemia or hyperlipidemia; db/db mice were treated with phlorizin, which selectively lowered plasma glucose, or bezafibrate, which selectively lowered plasma lipids. GIIS as well as the majority of the changes in gene expression were completely normalized by lowering glucose but were unaffected by lowering lipids. However, the restoration of GIIS was not accompanied by normalized uncoupling protein 2 or peroxisome proliferator-activated receptor γ mRNA levels, which were upregulated in db/db islets. These studies demonstrate that hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of β-cell differentiation and secretory function in db/db mice.
The β-cell is a highly specialized cell with a unique differentiation that optimizes glucose-induced insulin secretion (GIIS). Here, we evaluated changes in gene expression that accompany β-cell dysfunction in the db/db mouse model of type 2 diabetes. In db/db islets, mRNA levels of many genes implicated in β-cell glucose sensing were progressively reduced with time, as were several transcription factors important for the maintenance of β-cell differentiation. Conversely, genes normally suppressed in β-cells, such as a variety of stress response mediators and inhibitor of differentiation/DNA binding 1, a gene capable of inhibiting differentiation, were markedly increased. We assessed whether this global alteration in the pattern of β-cell gene expression was related more to chronic hyperglycemia or hyperlipidemia; db/db mice were treated with phlorizin, which selectively lowered plasma glucose, or bezafibrate, which selectively lowered plasma lipids. GIIS as well as the majority of the changes in gene expression were completely normalized by lowering glucose but were unaffected by lowering lipids. However, the restoration of GIIS was not accompanied by normalized uncoupling protein 2 or peroxisome proliferator–activated receptor γ mRNA levels, which were upregulated in db/db islets. These studies demonstrate that hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of β-cell differentiation and secretory function in db/db mice.
The beta-cell is a highly specialized cell with a unique differentiation that optimizes glucose-induced insulin secretion (GIIS). Here, we evaluated changes in gene expression that accompany beta-cell dysfunction in the db/db mouse model of type 2 diabetes. In db/db islets, mRNA levels of many genes implicated in beta-cell glucose sensing were progressively reduced with time, as were several transcription factors important for the maintenance of beta-cell differentiation. Conversely, genes normally suppressed in beta-cells, such as a variety of stress response mediators and inhibitor of differentiation/DNA binding 1, a gene capable of inhibiting differentiation, were markedly increased. We assessed whether this global alteration in the pattern of beta-cell gene expression was related more to chronic hyperglycemia or hyperlipidemia; db/db mice were treated with phlorizin, which selectively lowered plasma glucose, or bezafibrate, which selectively lowered plasma lipids. GIIS as well as the majority of the changes in gene expression were completely normalized by lowering glucose but were unaffected by lowering lipids. However, the restoration of GIIS was not accompanied by normalized uncoupling protein 2 or peroxisome proliferator-activated receptor gamma mRNA levels, which were upregulated in db/db islets. These studies demonstrate that hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of beta-cell differentiation and secretory function in db/db mice.
Chronic Hyperglycemia, Independent of Plasma Lipid Levels, Is Sufficient for the Loss of β-Cell Differentiation and Secretory Function in the db/db Mouse Model of Diabetes Cecilie Kjørholt , Mia C. Åkerfeldt , Trevor J. Biden and D. Ross Laybutt From the Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent’s Hospital, Sydney, Australia Address correspondence and reprint requests to Ross Laybutt, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, Sydney 2010, Australia. E-mail: r.laybutt{at}garvan.org.au Abstract The β-cell is a highly specialized cell with a unique differentiation that optimizes glucose-induced insulin secretion (GIIS). Here, we evaluated changes in gene expression that accompany β-cell dysfunction in the db/db mouse model of type 2 diabetes. In db/db islets, mRNA levels of many genes implicated in β-cell glucose sensing were progressively reduced with time, as were several transcription factors important for the maintenance of β-cell differentiation. Conversely, genes normally suppressed in β-cells, such as a variety of stress response mediators and inhibitor of differentiation/DNA binding 1, a gene capable of inhibiting differentiation, were markedly increased. We assessed whether this global alteration in the pattern of β-cell gene expression was related more to chronic hyperglycemia or hyperlipidemia; db/db mice were treated with phlorizin, which selectively lowered plasma glucose, or bezafibrate, which selectively lowered plasma lipids. GIIS as well as the majority of the changes in gene expression were completely normalized by lowering glucose but were unaffected by lowering lipids. However, the restoration of GIIS was not accompanied by normalized uncoupling protein 2 or peroxisome proliferator–activated receptor γ mRNA levels, which were upregulated in db/db islets. These studies demonstrate that hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of β-cell differentiation and secretory function in db/db mice. ATF-3, activating transcription factor 3 Β2/NeuroD, β-cell E-box trans-activator 2 CPT-1, carnitine palmitoyl transferase 1 GIIS, glucose-induced insulin secretion HNF1α, hepatocyte nuclear factor 1α IAPP, islet amyloid polypeptide ID-1, inhibitor of differentiation/DNA binding 1 KRHB, Krebs-Ringer HEPES buffer mGPDH, mitochondrial glycerol phosphate dehydrogenase NEFA, nonesterified fatty acid PDX-1, pancreatic duodenal homeobox-1 PPAR, peroxisome proliferator–activated receptor SNAP25, synaptosomal-associated protein of 25 kDa UCP-2, uncoupling protein 2 Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted June 3, 2005. Received April 19, 2005. DIABETES
Audience Professional
Author Cecilie Kjørholt
D. Ross Laybutt
Mia C. Åkerfeldt
Trevor J. Biden
Author_xml – sequence: 1
  givenname: Cecilie
  surname: KJØRHOLT
  fullname: KJØRHOLT, Cecilie
  organization: Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia
– sequence: 2
  givenname: Mia C
  surname: AKERFELDT
  fullname: AKERFELDT, Mia C
  organization: Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia
– sequence: 3
  givenname: Trevor J
  surname: BIDEN
  fullname: BIDEN, Trevor J
  organization: Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia
– sequence: 4
  givenname: D. Ross
  surname: LAYBUTT
  fullname: LAYBUTT, D. Ross
  organization: Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia
BackLink http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17075837$$DView record in Pascal Francis
https://www.ncbi.nlm.nih.gov/pubmed/16123366$$D View this record in MEDLINE/PubMed
BookMark eNptkt2KEzEUx4OsuN3VF_BCcqMgOt0kM0lmLpfuJ4worIJ3QyY5aSPTTDeZ0e07eeWD-Eym20pZKAdO4PD7n5PzcYKOfO8BodeUTFmeyzPjVAsDxCkvptWUSc6foQmt8irLmfx-hCaEUJZRWcljdBLjD0KISPYCHVNBUwYhJuj3bBF67zS-Wa8gzLu1hqVTH_GtN7CC5PyAe4u_dCouFa7dyhlcw0_oYmIivhutddptKNsHPCwA132MG8nfP9kMug5fOGshJMKpwfUeK2_wHegAQx_W-Gr0-jHs_KPatGemxZ_6MULyBrpNqotdoy_Rc6u6CK927yn6dnX5dXaT1Z-vb2fndaY5Y0NWSkWVkIa3hipTiIqzsqCiYjSnhklTlAIkKaluuSnbtiqkYtwCEAFMqIrnp-jdNu8q9PcjxKFZuqhTM8pD-lkjSk5zWZUJzLbgXHXQOG_7ISg9Bw9BdWlZ1qXwOc3TuAnJ88RPD_DJTJq6Pih4_0SQmAEehrkaY2zK6_opy7asDmkFAWyzCm6pwrqhpNkcTPP_YBpeNFWzOZgkerNrdWyXYPaS3YUk4O0OUFGrzgbltYt7ThLJy1wm7sOWW7j54pcLsK92oOw_6uvb9g
CODEN DIAEAZ
CitedBy_id crossref_primary_10_1016_j_semcdb_2020_01_003
crossref_primary_10_1111_j_1463_1326_2010_01291_x
crossref_primary_10_1016_j_ejphar_2008_11_017
crossref_primary_10_1016_j_metabol_2024_155813
crossref_primary_10_1016_j_tem_2014_01_003
crossref_primary_10_1007_s00125_012_2776_x
crossref_primary_10_2337_db12_0701
crossref_primary_10_1016_j_devcel_2015_10_019
crossref_primary_10_1097_GME_0b013e31828f5e3c
crossref_primary_10_2337_db11_1084
crossref_primary_10_3390_ijms23095104
crossref_primary_10_3390_metabo11040218
crossref_primary_10_1124_jpet_106_115337
crossref_primary_10_1016_S2213_8587_20_30022_X
crossref_primary_10_1210_en_2016_1393
crossref_primary_10_3390_biology10030176
crossref_primary_10_1016_j_jcyt_2021_01_005
crossref_primary_10_1016_j_bbrc_2015_10_038
crossref_primary_10_1016_j_jep_2008_09_036
crossref_primary_10_1111_j_1463_1326_2011_01445_x
crossref_primary_10_1210_en_2012_1425
crossref_primary_10_3390_ijms23052846
crossref_primary_10_1016_j_mce_2012_08_003
crossref_primary_10_1111_j_2040_1124_2010_00021_x
crossref_primary_10_2337_db19_0138
crossref_primary_10_3390_ijms23010324
crossref_primary_10_1007_s00125_011_2139_z
crossref_primary_10_1111_j_1872_034X_2007_00069_x
crossref_primary_10_1152_ajpendo_00145_2005
crossref_primary_10_3390_biom12091228
crossref_primary_10_3389_fendo_2020_00378
crossref_primary_10_1111_j_1463_1326_2008_00940_x
crossref_primary_10_1016_j_nut_2008_12_010
crossref_primary_10_1210_en_2013_1523
crossref_primary_10_1016_j_vascn_2010_04_001
crossref_primary_10_1016_j_jaut_2016_02_001
crossref_primary_10_1016_j_mce_2019_110524
crossref_primary_10_1371_journal_pone_0029807
crossref_primary_10_1016_j_jgg_2022_03_002
crossref_primary_10_1007_s00125_015_3503_1
crossref_primary_10_4093_dmj_2011_35_5_458
crossref_primary_10_3390_cells12050773
crossref_primary_10_1152_ajpendo_90235_2008
crossref_primary_10_1371_journal_pone_0082813
crossref_primary_10_1111_nyas_12031
crossref_primary_10_1016_j_molmet_2017_04_003
crossref_primary_10_1111_j_1463_1326_2009_01156_x
crossref_primary_10_1126_sciadv_aba0145
crossref_primary_10_1530_JME_13_0016
crossref_primary_10_1016_j_cytogfr_2015_12_009
crossref_primary_10_1016_j_ejphar_2008_04_018
crossref_primary_10_1016_S1001_9294_09_60023_7
crossref_primary_10_1210_me_2011_1256
crossref_primary_10_1002_dmrr_653
crossref_primary_10_1530_JOE_17_0516
crossref_primary_10_1007_s00125_011_2197_2
crossref_primary_10_1186_s12974_024_03021_x
crossref_primary_10_1111_dom_12732
crossref_primary_10_3727_096368915X687958
crossref_primary_10_1172_JCI64151
crossref_primary_10_1155_2014_618652
crossref_primary_10_1038_ncomms15652
crossref_primary_10_1155_2016_6035046
crossref_primary_10_1111_j_1476_5381_2009_00145_x
crossref_primary_10_3389_fgene_2014_00193
crossref_primary_10_1152_ajpendo_00388_2009
crossref_primary_10_2337_db07_1252
crossref_primary_10_1016_j_taap_2018_12_011
crossref_primary_10_1038_s41467_022_32162_x
crossref_primary_10_1038_s41419_023_05906_w
crossref_primary_10_2337_db18_0201
crossref_primary_10_1111_j_1872_034X_2008_00363_x
crossref_primary_10_1016_j_tem_2014_02_003
crossref_primary_10_2337_db06_1033
crossref_primary_10_2337_db10_0450
crossref_primary_10_2337_db07_1802
crossref_primary_10_1016_j_npep_2006_08_002
crossref_primary_10_1096_fj_202100009R
crossref_primary_10_1007_s00125_007_0749_2
crossref_primary_10_1016_j_molmet_2018_01_010
crossref_primary_10_1016_j_bbrc_2006_10_076
crossref_primary_10_1007_s00125_006_0590_z
crossref_primary_10_1007_s00125_022_05669_7
crossref_primary_10_1038_ncomms11740
crossref_primary_10_2337_db11_1179
crossref_primary_10_2337_db14_1752
crossref_primary_10_1371_journal_pone_0252607
crossref_primary_10_1038_aps_2013_196
crossref_primary_10_2337_db11_0083
crossref_primary_10_1007_s00424_008_0548_8
crossref_primary_10_1016_j_molmet_2024_101955
crossref_primary_10_1111_dom_14459
crossref_primary_10_1074_jbc_M114_595579
crossref_primary_10_1016_j_phymed_2024_155396
crossref_primary_10_1111_1440_1681_12368
crossref_primary_10_1210_me_2008_0482
crossref_primary_10_2337_db20_0881
crossref_primary_10_1101_gad_227785_113
crossref_primary_10_1007_s00125_016_3942_3
crossref_primary_10_1080_19382014_2018_1503027
crossref_primary_10_1155_2018_4561309
crossref_primary_10_3390_nu13051635
crossref_primary_10_1111_j_1463_1326_2009_01112_x
crossref_primary_10_1016_j_celrep_2019_08_073
crossref_primary_10_2337_db13_0272
crossref_primary_10_1007_s00125_014_3226_8
crossref_primary_10_1111_j_1463_1326_2012_01655_x
crossref_primary_10_1111_dom_13378
crossref_primary_10_1111_1753_0407_12022
crossref_primary_10_1210_me_2014_1299
crossref_primary_10_2337_db11_1054
crossref_primary_10_1016_j_celrep_2022_110872
crossref_primary_10_1016_j_cmet_2007_08_012
Cites_doi 10.1128/MCB.23.20.7222-7229.2003
10.1007/s001250051643
10.2337/diabetes.53.4.1007
10.1016/S0303-7207(97)00190-1
10.1210/en.2003-0410
10.1073/pnas.87.17.6492
10.1093/jn/113.1.184
10.1242/dev.127.24.5533
10.1172/JCI420
10.1016/S0021-9258(17)32299-8
10.1007/s00125-004-1454-z
10.2337/diabetes.50.1.63
10.1186/1743-7075-2-1
10.1016/S0021-9258(17)37581-6
10.2337/diabetes.50.11.2481
10.1152/ajpendo.00426.2003
10.1073/pnas.91.23.10878
10.2337/diabetes.50.2007.S89
10.1074/jbc.272.48.30261
10.2337/diabetes.45.5.580
10.1007/s00109-003-0450-y
10.2337/diab.40.2.166
10.1111/j.1749-6632.1999.tb07798.x
10.1083/jcb.128.6.1019
10.1016/S1535-6108(03)00141-7
10.2337/diabetes.45.11.1626
10.2337/diabetes.51.4.977
10.1128/mcb.11.3.1734-1738.1991
10.1073/pnas.122686299
10.1172/JCI115858
10.1073/pnas.91.20.9253
10.2337/diabetes.44.12.1447
10.1016/j.bbrc.2004.03.067
10.1074/jbc.274.20.14112
10.1128/MCB.14.10.6704
10.1210/jc.84.2.670
10.2337/diabetes.52.1.1
10.1074/jbc.M100986200
10.1074/jbc.M210581200
10.1016/S0092-8674(01)00378-6
10.2337/diabetes.51.3.662
10.2337/diabetes.48.7.1482
10.1007/BF00429772
10.1073/pnas.95.5.2498
10.1161/01.CIR.98.19.2088
10.1210/jcem-42-2-222
10.1097/00007890-198709000-00015
10.1016/j.metabol.2003.11.021
10.1007/s00125-004-1368-9
10.1016/S0891-5849(99)00084-2
10.1073/pnas.0305683101
10.2337/diabetes.50.2007.S154
10.2337/diabetes.54.3.727
10.2337/diabetes.51.2.413
10.1152/ajpendo.00149.2002
10.2337/diabetes.50.10.2181
ContentType Journal Article
Copyright 2005 INIST-CNRS
COPYRIGHT 2005 American Diabetes Association
Copyright_xml – notice: 2005 INIST-CNRS
– notice: COPYRIGHT 2005 American Diabetes Association
DBID IQODW
CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
8GL
7X8
DOI 10.2337/diabetes.54.9.2755
DatabaseName Pascal-Francis
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
Gale In Context: High School
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
MEDLINE - Academic
DatabaseTitleList
CrossRef
MEDLINE - Academic
MEDLINE

Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1939-327X
EndPage 2763
ExternalDocumentID A136120033
10_2337_diabetes_54_9_2755
16123366
17075837
diabetes_54_9_2755
Genre Research Support, Non-U.S. Gov't
Journal Article
GeographicLocations Australia
GeographicLocations_xml – name: Australia
GroupedDBID -
08R
0R
1AW
29F
2WC
3V.
4.4
53G
55
5GY
5RE
5RS
5VS
7RV
7X7
88E
88I
8AF
8AO
8C1
8F7
8FE
8FH
8FI
8FJ
8G5
8GL
8R4
8R5
AAQQT
AAWTL
AAYEP
AAYJJ
ABFLS
ABOCM
ABPTK
ABUWG
ACDCL
ACGOD
ACPRK
ADACO
ADBBV
ADBIT
AENEX
AFFNX
AFKRA
AHMBA
ALMA_UNASSIGNED_HOLDINGS
AZQEC
BAWUL
BBAFP
BBNVY
BCR
BCU
BEC
BENPR
BES
BHPHI
BKEYQ
BKNYI
BLC
BPHCQ
BVXVI
C1A
CS3
DIK
DU5
DWQXO
E3Z
EBS
EDB
EJD
EX3
F5P
FRP
FYUFA
GICCO
GJ
GNUQQ
GUQSH
GX1
H13
HCIFZ
HZ
IAG
IAO
IEA
IHR
INH
INR
IOF
IPO
J5H
K-O
K9-
KM
KQ8
L7B
LK8
M0R
M1P
M2O
M2P
M2Q
M5
M7P
MBDVC
O0-
O9-
OB3
OBH
OK1
OVD
P2P
PADUT
PCD
PEA
PQEST
PQQKQ
PQUKI
PRINS
PROAC
PSQYO
Q2X
RHF
RHI
RPM
S0X
SJFOW
SJN
SV3
TDI
WH7
WOQ
WOW
X7M
XZ
ZA5
ZGI
ZXP
ZY1
---
.55
.GJ
.XZ
08P
0R~
18M
1CY
354
6PF
AAKAS
AAUGY
AAYOK
ACGFO
ADZCM
AEGXH
AERZD
AFHIN
AI.
AIAGR
BTFSW
CCPQU
EMOBN
HZ~
H~9
IQODW
ITC
K2M
M5~
MVM
N4W
NAPCQ
O5R
O5S
OHH
TEORI
TR2
UKHRP
VH1
VVN
W8F
XOL
YFH
YHG
YOC
YQJ
~KM
AIZAD
ALIPV
CGR
CUY
CVF
ECM
EIF
HMCUK
NPM
AAYXX
CITATION
7X8
ID FETCH-LOGICAL-c522t-87a1a67d5bd1ad46952841692131d27d486e7081cb5d8bb947a25fee06e26a953
ISSN 0012-1797
IngestDate Fri Oct 25 05:03:31 EDT 2024
Thu Nov 14 22:02:10 EST 2024
Wed Nov 13 00:16:45 EST 2024
Thu Aug 01 19:33:57 EDT 2024
Fri Dec 06 04:21:00 EST 2024
Sat Sep 28 08:38:40 EDT 2024
Sun Oct 22 16:06:41 EDT 2023
Fri Jan 15 19:45:53 EST 2021
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 9
Keywords Endocrinopathy
Animal model
Diabetes mellitus
Langerhans islet
Rodentia
Lipids
Cell differentiation
Vertebrata
Chronic
Hyperglycemia
Mammalia
Mouse
Animal
β Cell
Endocrine pancreas
Language English
License CC BY 4.0
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c522t-87a1a67d5bd1ad46952841692131d27d486e7081cb5d8bb947a25fee06e26a953
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
OpenAccessLink https://diabetesjournals.org/diabetes/article-pdf/54/9/2755/383074/zdb00905002755.pdf
PMID 16123366
PQID 68513798
PQPubID 23479
PageCount 9
ParticipantIDs proquest_miscellaneous_68513798
pubmed_primary_16123366
gale_incontextgauss_8GL_A136120033
highwire_diabetes_diabetes_54_9_2755
gale_infotracgeneralonefile_A136120033
crossref_primary_10_2337_diabetes_54_9_2755
pascalfrancis_primary_17075837
gale_infotracacademiconefile_A136120033
ProviderPackageCode RHF
RHI
PublicationCentury 2000
PublicationDate 2005-09-01
PublicationDateYYYYMMDD 2005-09-01
PublicationDate_xml – month: 09
  year: 2005
  text: 2005-09-01
  day: 01
PublicationDecade 2000
PublicationPlace Alexandria, VA
PublicationPlace_xml – name: Alexandria, VA
– name: United States
PublicationTitle Diabetes (New York, N.Y.)
PublicationTitleAlternate Diabetes
PublicationYear 2005
Publisher American Diabetes Association
Publisher_xml – name: American Diabetes Association
References 21949000 - Diabetes. 2011 Oct;60(10):2455-6
2022031208155745000_R30
2022031208155745000_R39
2022031208155745000_R38
2022031208155745000_R37
2022031208155745000_R36
2022031208155745000_R35
2022031208155745000_R34
2022031208155745000_R33
2022031208155745000_R32
2022031208155745000_R31
2022031208155745000_R41
2022031208155745000_R40
2022031208155745000_R6
2022031208155745000_R7
2022031208155745000_R8
2022031208155745000_R9
2022031208155745000_R2
2022031208155745000_R3
2022031208155745000_R4
2022031208155745000_R5
2022031208155745000_R49
2022031208155745000_R48
2022031208155745000_R47
2022031208155745000_R46
2022031208155745000_R45
2022031208155745000_R44
2022031208155745000_R43
2022031208155745000_R42
2022031208155745000_R52
2022031208155745000_R51
2022031208155745000_R50
2022031208155745000_R1
2022031208155745000_R19
2022031208155745000_R18
2022031208155745000_R17
2022031208155745000_R16
2022031208155745000_R15
2022031208155745000_R14
2022031208155745000_R13
2022031208155745000_R12
2022031208155745000_R56
2022031208155745000_R11
2022031208155745000_R55
2022031208155745000_R10
2022031208155745000_R54
2022031208155745000_R53
2022031208155745000_R29
2022031208155745000_R28
2022031208155745000_R27
2022031208155745000_R26
2022031208155745000_R25
2022031208155745000_R24
2022031208155745000_R23
2022031208155745000_R22
2022031208155745000_R21
2022031208155745000_R20
References_xml – ident: 2022031208155745000_R13
  doi: 10.1128/MCB.23.20.7222-7229.2003
– ident: 2022031208155745000_R11
  doi: 10.1007/s001250051643
– ident: 2022031208155745000_R52
  doi: 10.2337/diabetes.53.4.1007
– ident: 2022031208155745000_R21
  doi: 10.1016/S0303-7207(97)00190-1
– ident: 2022031208155745000_R54
  doi: 10.1210/en.2003-0410
– ident: 2022031208155745000_R16
  doi: 10.1073/pnas.87.17.6492
– ident: 2022031208155745000_R8
  doi: 10.1093/jn/113.1.184
– ident: 2022031208155745000_R34
  doi: 10.1242/dev.127.24.5533
– ident: 2022031208155745000_R49
  doi: 10.1172/JCI420
– ident: 2022031208155745000_R19
  doi: 10.1016/S0021-9258(17)32299-8
– ident: 2022031208155745000_R45
  doi: 10.1007/s00125-004-1454-z
– ident: 2022031208155745000_R43
  doi: 10.2337/diabetes.50.1.63
– ident: 2022031208155745000_R14
  doi: 10.1186/1743-7075-2-1
– ident: 2022031208155745000_R22
  doi: 10.1016/S0021-9258(17)37581-6
– ident: 2022031208155745000_R46
  doi: 10.2337/diabetes.50.11.2481
– ident: 2022031208155745000_R31
  doi: 10.1152/ajpendo.00426.2003
– ident: 2022031208155745000_R47
  doi: 10.1073/pnas.91.23.10878
– ident: 2022031208155745000_R56
  doi: 10.2337/diabetes.50.2007.S89
– ident: 2022031208155745000_R48
  doi: 10.1074/jbc.272.48.30261
– ident: 2022031208155745000_R6
  doi: 10.2337/diabetes.45.5.580
– ident: 2022031208155745000_R25
  doi: 10.1007/s00109-003-0450-y
– ident: 2022031208155745000_R3
  doi: 10.2337/diab.40.2.166
– ident: 2022031208155745000_R7
  doi: 10.1111/j.1749-6632.1999.tb07798.x
– ident: 2022031208155745000_R23
  doi: 10.1083/jcb.128.6.1019
– ident: 2022031208155745000_R12
  doi: 10.1016/S1535-6108(03)00141-7
– ident: 2022031208155745000_R55
  doi: 10.2337/diabetes.45.11.1626
– ident: 2022031208155745000_R51
  doi: 10.2337/diabetes.51.4.977
– ident: 2022031208155745000_R36
  doi: 10.1128/mcb.11.3.1734-1738.1991
– ident: 2022031208155745000_R29
  doi: 10.1073/pnas.122686299
– ident: 2022031208155745000_R15
  doi: 10.1172/JCI115858
– ident: 2022031208155745000_R38
  doi: 10.1073/pnas.91.20.9253
– ident: 2022031208155745000_R4
  doi: 10.2337/diabetes.44.12.1447
– ident: 2022031208155745000_R24
  doi: 10.1016/j.bbrc.2004.03.067
– ident: 2022031208155745000_R32
  doi: 10.1074/jbc.274.20.14112
– ident: 2022031208155745000_R37
  doi: 10.1128/MCB.14.10.6704
– ident: 2022031208155745000_R41
  doi: 10.1210/jc.84.2.670
– ident: 2022031208155745000_R26
  doi: 10.2337/diabetes.52.1.1
– ident: 2022031208155745000_R28
  doi: 10.1074/jbc.M100986200
– ident: 2022031208155745000_R33
  doi: 10.1074/jbc.M210581200
– ident: 2022031208155745000_R18
  doi: 10.1016/S0092-8674(01)00378-6
– ident: 2022031208155745000_R53
  doi: 10.2337/diabetes.51.3.662
– ident: 2022031208155745000_R17
  doi: 10.2337/diabetes.48.7.1482
– ident: 2022031208155745000_R20
  doi: 10.1007/BF00429772
– ident: 2022031208155745000_R50
  doi: 10.1073/pnas.95.5.2498
– ident: 2022031208155745000_R30
  doi: 10.1161/01.CIR.98.19.2088
– ident: 2022031208155745000_R2
  doi: 10.1210/jcem-42-2-222
– ident: 2022031208155745000_R39
  doi: 10.1097/00007890-198709000-00015
– ident: 2022031208155745000_R9
  doi: 10.1016/j.metabol.2003.11.021
– ident: 2022031208155745000_R35
  doi: 10.1007/s00125-004-1368-9
– ident: 2022031208155745000_R40
  doi: 10.1016/S0891-5849(99)00084-2
– ident: 2022031208155745000_R42
  doi: 10.1073/pnas.0305683101
– ident: 2022031208155745000_R5
  doi: 10.2337/diabetes.50.2007.S154
– ident: 2022031208155745000_R44
  doi: 10.2337/diabetes.54.3.727
– ident: 2022031208155745000_R27
  doi: 10.2337/diabetes.51.2.413
– ident: 2022031208155745000_R10
  doi: 10.1152/ajpendo.00149.2002
– ident: 2022031208155745000_R1
  doi: 10.2337/diabetes.50.10.2181
SSID ssj0006060
Score 2.252775
Snippet Chronic Hyperglycemia, Independent of Plasma Lipid Levels, Is Sufficient for the Loss of β-Cell Differentiation and Secretory Function in the db/db Mouse Model...
The beta-cell is a highly specialized cell with a unique differentiation that optimizes glucose-induced insulin secretion (GIIS). Here, we evaluated changes in...
The β-cell is a highly specialized cell with a unique differentiation that optimizes glucose-induced insulin secretion (GIIS). Here, we evaluated changes in...
SourceID proquest
gale
crossref
pubmed
pascalfrancis
highwire
SourceType Aggregation Database
Index Database
Publisher
StartPage 2755
SubjectTerms Aging
Animals
Biological and medical sciences
Blood lipids
Cell Differentiation - physiology
Diabetes Mellitus - physiopathology
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Gene Expression Regulation - physiology
Hyperglycemia
Hyperglycemia - physiopathology
Insulin - metabolism
Islets of Langerhans - cytology
Islets of Langerhans - metabolism
Lipids - blood
Medical sciences
Mice
Observations
Pancreatic beta cells
RNA, Messenger - metabolism
Title Chronic Hyperglycemia, Independent of Plasma Lipid Levels, Is Sufficient for the Loss of β-Cell Differentiation and Secretory Function in the db/db Mouse Model of Diabetes
URI http://diabetes.diabetesjournals.org/content/54/9/2755.abstract
https://www.ncbi.nlm.nih.gov/pubmed/16123366
https://search.proquest.com/docview/68513798
Volume 54
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3bbtQwELVKKyFeEHeWS7FQBQ9ht02cOMljr1SwLajaSvsW2bFTAtvdapNFKh_FV_BhzMTOZUsRl5coiuzEyZyMZ8bjM4RsiDTlQsitvnQj2QftB3pQBarP0yyQLBWKCdzvfHTMD0_9d-NgvLLyo5O1tCjlIP127b6S_5EqXAO54i7Zf5Bsc1O4AOcgXziChOH4VzK2zLbOJ3Am52eTy1Sfm9zXvCluWy30X4CJfC6cSX6RK2eCaUKV9PLCKRYVhUTF0GTzDScwbWInqUvRx7h-U0SlNGKs1hsKNDerBXqcGbsZk0rCCynpYExBm0o7eLs6yNu1hvc6gd-rJYE6IYr3n3E5fyeag6Y2WSo6zSd5C9Yvep7piTKZJ7loI787uVWro7n-Cu_XBMWH4lIuzLrYnnMyK5ajH0GT3tVodNdDitWwq9ENLbVFbtxVz6HhBLZTvWeV69VpxGMVEUH9YQaBP4gHbd8uZ_fxh-TgdDhMRvvj0Q2yhnSM_ipZ29k__njSWATgJJqtUHasZvMWPmXz12csGUi1mVBzV2Pqrijg781M2ZXf-0WVfTS6Q25bx4ZuG5TeJSt6eo_cPLKpG_fJdwtWugTWN7QDVTrLqIEqraBKDVShTUFboFIAKgWgUQQqdmmASq8AlQJQaQNUWgMVHln1V3JTSVrBlFYwxZvVX-oBOT3YH-0e9m2xkH4KLkQJs7pwBQ9VIJUrlM_jwMMV9dhzmau8UPkR1yHYv6kMVCRl7IfCCzKtt7j2uIgD9pCsTmdT_ZhQlsIkKFgYcgn2uogkZ77vb6ksCJjivuoRp5ZQcmE4YRLwpVGeST3KJPCTOEF59shLFGKCZCtTzOY6E4uiSKK3w2TbZeBgYDnFHnltG2Wzci5SYTfHwICQn22p5aullmeGnf66hhs1atpRXTe89SVEtW8UgjcRsbBHXtQQS2DqQXGKqQbZJBy8NRbGUY88Mshr-yKpE-P8yR_7PiW32t_6GVkt5wv9HMz8Uq6TG-E4hGO0667bP-onMT8GGg
link.rule.ids 314,780,784,27924,27925,31720,33267,33745
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Chronic+hyperglycemia%2C+independent+of+plasma+lipid+levels%2C+is+sufficient+for+the+loss+of+beta-cell+differentiation+and+secretory+function+in+the+db%2Fdb+mouse+model+of+diabetes&rft.jtitle=Diabetes+%28New+York%2C+N.Y.%29&rft.au=Kj%C3%B8rholt%2C+Cecilie&rft.au=Akerfeldt%2C+Mia+C&rft.au=Biden%2C+Trevor+J&rft.au=Laybutt%2C+D+Ross&rft.date=2005-09-01&rft.issn=0012-1797&rft.volume=54&rft.issue=9&rft.spage=2755&rft.epage=2763&rft_id=info:doi/10.2337%2Fdiabetes.54.9.2755&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0012-1797&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0012-1797&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0012-1797&client=summon