PMID- 29546577
OWN - NLM
STAT- MEDLINE
DCOM- 20180717
LR  - 20181202
IS  - 1432-5233 (Electronic)
IS  - 0940-5429 (Linking)
VI  - 55
IP  - 6
DP  - 2018 Jun
TI  - Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with 
      type 2 diabetes.
PG  - 585-592
LID - 10.1007/s00592-018-1130-2 [doi]
AB  - AIMS: 5-Aminoimidazole-4-carboxamide riboside (AICAR) is an endogenous activator 
      of AMPK, a central regulator of energy homeostasis. Loss and/or reduction of AMPK 
      signaling plays an important role in the development of insulin resistance in 
      type 2 diabetes. The loss of AMPK in diabetes could be due to a loss of AICAR. 
      The aim of this study was to characterize urine levels of AICAR in diabetes and 
      determine whether an association exists with respect to late complications, e.g., 
      retinopathy, nephropathy and neuropathy. METHODS: Urine AICAR was measured by 
      liquid chromatography tandem mass spectrometry in 223 patients consisting of 5 
      healthy controls, 63 patients with pre-diabetes, 29 patients with newly diagnosed 
      type 2 diabetes and 126 patients with long-standing type 2 diabetes. For 
      statistical analyses, nonparametric Kruskal-Wallis test, one-way ANOVA and 
      multivariate regression analysis were performed to investigate the associations 
      of urinary AICAR excretion within different groups and different clinical 
      parameters. RESULTS: The mean urine AICAR for all 223 patients was 
      694.7 +/- 641.1 ng/ml. There was no significant difference in urine AICAR between 
      the control and patients with diabetes (592.3 +/- 345.1 vs. 697.1 +/- 646.5 ng/ml). 
      No association between any of the biochemical and/or clinical parameters measured 
      and urine AICAR was found, with the exception of age of patient (R = - 0.34; 
      p < 0.01) and estimated glomerular filtration rate (R = 0.19; p = 0.039). These 
      results were confirmed additionally by linear regression analysis. CONCLUSIONS: 
      Clinical diabetes is not associated with a change in endogenous AICAR levels. 
      Loss of AICAR may therefore not be a mechanism by which AMPK signaling is reduced 
      in diabetes.
FAU - Mendler, Michael
AU  - Mendler M
AD  - Department of Medicine I and Clinical Chemistry, University Hospital of 
      Heidelberg, INF 410, Heidelberg, Germany. michael.mendler@med.uni-heidelberg.de.
FAU - Kopf, Stefan
AU  - Kopf S
AD  - Department of Medicine I and Clinical Chemistry, University Hospital of 
      Heidelberg, INF 410, Heidelberg, Germany.
AD  - German Center for Diabetes Research (DZD), Ingolstadter Landstrasse 1, 85764, 
      Neuherberg, Germany.
FAU - Groener, Jan B
AU  - Groener JB
AD  - Department of Medicine I and Clinical Chemistry, University Hospital of 
      Heidelberg, INF 410, Heidelberg, Germany.
AD  - German Center for Diabetes Research (DZD), Ingolstadter Landstrasse 1, 85764, 
      Neuherberg, Germany.
FAU - Riedinger, Christin
AU  - Riedinger C
AD  - Department of Medicine I and Clinical Chemistry, University Hospital of 
      Heidelberg, INF 410, Heidelberg, Germany.
FAU - Fleming, Thomas H
AU  - Fleming TH
AD  - Department of Medicine I and Clinical Chemistry, University Hospital of 
      Heidelberg, INF 410, Heidelberg, Germany.
AD  - German Center for Diabetes Research (DZD), Ingolstadter Landstrasse 1, 85764, 
      Neuherberg, Germany.
FAU - Nawroth, Peter P
AU  - Nawroth PP
AD  - Department of Medicine I and Clinical Chemistry, University Hospital of 
      Heidelberg, INF 410, Heidelberg, Germany.
AD  - German Center for Diabetes Research (DZD), Ingolstadter Landstrasse 1, 85764, 
      Neuherberg, Germany.
AD  - Institute for Diabetes and Cancer, IDC Helmholtz Center Munich, Germany & Joint 
      Heidelberg-IDC Translational Diabetes Program, Neuherberg, Germany.
FAU - Okun, Jurgen G
AU  - Okun JG
AD  - Dietmar-Hopp Metabolic Center, Center for Child and Adolescent Medicine, 
      University of Heidelberg, Heidelberg, Germany.
LA  - eng
GR  - CRC1118/Deutsche Forschungsgemeinschaft/
GR  - CRC1118/Deutsche Forschungsgemeinschaft/
GR  - CRC1118/Deutsche Forschungsgemeinschaft/
GR  - CRC1118/Deutsche Forschungsgemeinschaft/
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20180315
PL  - Germany
TA  - Acta Diabetol
JT  - Acta diabetologica
JID - 9200299
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - Adenylate Kinase/metabolism
MH  - Adult
MH  - Aged
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/urine
MH  - Animals
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Diabetes Complications/metabolism/prevention & control/urine
MH  - Diabetes Mellitus, Type 2/complications/metabolism/prevention & control/*urine
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Prediabetic State/pathology/therapy/urine
MH  - Ribonucleotides/*urine
MH  - Risk Factors
MH  - Risk Reduction Behavior
MH  - Signal Transduction/physiology
OTO - NOTNLM
OT  - AICAR
OT  - AMPK
OT  - Diabetes
OT  - Late diabetic complications
OT  - Urine analysis
EDAT- 2018/03/17 06:00
MHDA- 2018/07/18 06:00
CRDT- 2018/03/17 06:00
PHST- 2017/11/27 00:00 [received]
PHST- 2018/03/08 00:00 [accepted]
PHST- 2018/03/17 06:00 [pubmed]
PHST- 2018/07/18 06:00 [medline]
PHST- 2018/03/17 06:00 [entrez]
AID - 10.1007/s00592-018-1130-2 [pii]
AID - 10.1007/s00592-018-1130-2 [doi]
PST - ppublish
SO  - Acta Diabetol. 2018 Jun;55(6):585-592. doi: 10.1007/s00592-018-1130-2. Epub 2018 
      Mar 15.