PMID- 19637187
OWN - NLM
STAT- MEDLINE
DCOM- 20091020
LR  - 20131121
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 50
IP  - 4
DP  - 2009 Oct
TI  - Abnormal hepatic energy homeostasis in type 2 diabetes.
PG  - 1079-86
LID - 10.1002/hep.23093 [doi]
AB  - Increased hepatocellular lipids relate to insulin resistance and are typical for 
      individuals with type 2 diabetes mellitus (T2DM). Steatosis and T2DM have been 
      further associated with impaired muscular adenosine triphosphate (ATP) turnover 
      indicating reduced mitochondrial fitness. Thus, we tested the hypothesis that 
      hepatic energy metabolism could be impaired even in metabolically well-controlled 
      T2DM. We measured hepatic lipid volume fraction (HLVF) and absolute 
      concentrations of gammaATP, inorganic phosphate (Pi), phosphomonoesters and 
      phosphodiesters using noninvasive (1)H/ (31)P magnetic resonance spectroscopy in 
      individuals with T2DM (58 +/- 6 years, 27 +/- 3 kg/m (2)), and age-matched and 
      body mass index-matched (mCON; 61 +/- 4 years, 26 +/- 4 kg/m (2)) and young lean 
      humans (yCON; 25 +/- 3 years, 22 +/- 2 kg/m (2), P < 0.005, P < 0.05 versus T2DM 
      and mCON). Insulin-mediated whole-body glucose disposal (M) and endogenous 
      glucose production (iEGP) were assessed during euglycemic-hyperinsulinemic 
      clamps. Individuals with T2DM had 26% and 23% lower gammaATP (1.68 +/- 0.11; 2.26 
      +/- 0.20; 2.20 +/- 0.09 mmol/L; P < 0.05) than mCON and yCON individuals, 
      respectively. Further, they had 28% and 31% lower Pi than did individuals from 
      the mCON and yCON groups (0.96 +/- 0.06; 1.33 +/- 0.13; 1.41 +/- 0.07 mmol/L; P < 
      0.05). Phosphomonoesters, phosphodiesters, and liver aminotransferases did not 
      differ between groups. HLVF was not different between those from the T2DM and 
      mCON groups, but higher (P = 0.002) than in those from the yCON group. T2DM had 
      13-fold higher iEGP than mCON (P < 0.05). Even after adjustment for HLVF, hepatic 
      ATP and Pi related negatively to hepatic insulin sensitivity (iEGP) (r =-0.665, P 
      = 0.010, r =-0.680, P = 0.007) but not to whole-body insulin sensitivity. 
      CONCLUSION: These data suggest that impaired hepatic energy metabolism and 
      insulin resistance could precede the development of steatosis in individuals with 
      T2DM.
FAU - Szendroedi, Julia
AU  - Szendroedi J
AD  - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for 
      Diabetes Research, Heinrich Heine University Dusseldorf, Germany.
FAU - Chmelik, Marek
AU  - Chmelik M
FAU - Schmid, Albrecht Ingo
AU  - Schmid AI
FAU - Nowotny, Peter
AU  - Nowotny P
FAU - Brehm, Attila
AU  - Brehm A
FAU - Krssak, Martin
AU  - Krssak M
FAU - Moser, Ewald
AU  - Moser E
FAU - Roden, Michael
AU  - Roden M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Phosphates)
RN  - 27YLU75U4W (Phosphorus)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Aged
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*metabolism/physiopathology
MH  - Energy Metabolism/*physiology
MH  - Fatty Liver/etiology/metabolism
MH  - Female
MH  - Homeostasis/*physiology
MH  - Humans
MH  - Insulin Resistance/physiology
MH  - Lipid Metabolism/physiology
MH  - Liver/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Phosphates/metabolism
MH  - Phosphorus/metabolism
EDAT- 2009/07/29 09:00
MHDA- 2009/10/21 06:00
CRDT- 2009/07/29 09:00
PHST- 2009/07/29 09:00 [entrez]
PHST- 2009/07/29 09:00 [pubmed]
PHST- 2009/10/21 06:00 [medline]
AID - 10.1002/hep.23093 [doi]
PST - ppublish
SO  - Hepatology. 2009 Oct;50(4):1079-86. doi: 10.1002/hep.23093.