PMID- 16988889
OWN - NLM
STAT- MEDLINE
DCOM- 20070731
LR  - 20220716
IS  - 0300-8177 (Print)
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 299
IP  - 1-2
DP  - 2007 May
TI  - Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: role of 
      sarcolemmal substrate transporters.
PG  - 5-18
AB  - Cardiovascular disease is the primary cause of death in obesity and type-2 
      diabetes mellitus (T2DM). Alterations in substrate metabolism are believed to be 
      involved in the development of both cardiac dysfunction and insulin resistance in 
      these conditions. Under physiological circumstances the heart utilizes 
      predominantly long-chain fatty acids (LCFAs) (60-70%), with the remainder covered 
      by carbohydrates, i.e., glucose (20%) and lactate (10%). The cellular uptake of 
      both LCFA and glucose is regulated by the sarcolemmal amount of specific 
      transport proteins, i.e., fatty acid translocase (FAT)/CD36 and GLUT4, 
      respectively. These transport proteins are not only present at the sarcolemma, 
      but also in intracellular storage compartments. Both an increased workload and 
      the hormone insulin induce translocation of FAT/CD36 and GLUT4 to the sarcolemma. 
      In this review, recent findings on the insulin and contraction signalling 
      pathways involved in substrate uptake and utilization by cardiac myocytes under 
      physiological conditions are discussed. New insights in alterations in substrate 
      uptake and utilization during insulin resistance and its progression towards T2DM 
      suggest a pivotal role for substrate transporters. During the development of 
      obesity towards T2DM alterations in cardiac lipid homeostasis were found to 
      precede alterations in glucose homeostasis. In the early stages of T2DM, 
      relocation of FAT/CD36 to the sarcolemma is associated with the myocardial 
      accumulation of triacylglycerols (TAGs) eventually leading to an impaired 
      insulin-stimulated GLUT4-translocation. These novel insights may result in new 
      strategies for the prevention of development of cardiac dysfunction and insulin 
      resistance in obesity and T2DM.
FAU - Coort, Susan L M
AU  - Coort SL
AD  - Department of Molecular Genetics, Cardiovascular Research Institute Maastricht 
      (CARIM), Maastricht University, Maastricht, The Netherlands.
FAU - Bonen, Arend
AU  - Bonen A
FAU - van der Vusse, Ger J
AU  - van der Vusse GJ
FAU - Glatz, Jan F C
AU  - Glatz JF
FAU - Luiken, Joost J F P
AU  - Luiken JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Fatty Acids)
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Fatty Acids/metabolism
MH  - Glucose/metabolism
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Myocardium/*metabolism
MH  - Obesity/*metabolism
MH  - Sarcolemma/*metabolism
MH  - Signal Transduction
PMC - PMC1915649
EDAT- 2006/09/22 09:00
MHDA- 2007/08/01 09:00
PMCR- 2007/07/13
CRDT- 2006/09/22 09:00
PHST- 2006/09/22 09:00 [pubmed]
PHST- 2007/08/01 09:00 [medline]
PHST- 2006/09/22 09:00 [entrez]
PHST- 2007/07/13 00:00 [pmc-release]
AID - 9372 [pii]
AID - 10.1007/s11010-005-9030-5 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2007 May;299(1-2):5-18. doi: 10.1007/s11010-005-9030-5.