Myocardial uptake of iodine-125-labeled 15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid is decreased in chronic diabetic rats with changes in subcellular distribution.
Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (123I-BMIPP) is widely used to detect myocardial metabolic changes, but the preferred energy substrates in the myocardium would be expected to be altered in the presence of metabolic disorders such as diabetes mellitus (DM). We investigated the metabolism of branched-chain fatty acids in the myocardium of rats with DM. Streptozotocin-induced DM rats were examined 48 h (acute; AD) and 6 weeks (chronic; CD) after injection of streptozotocin. Hearts were excised 15 min or 60 min after injection of 0.185 MBq of 125I-BMIPP, followed by homogenization in an EDTA-Tris buffer. The homogenates were subjected to differential centrifugation to obtain the mitochondrial (MF) and cytoplasmic (CF) fractions. Myocardial 125I uptake tended to increase in the AD group, but the change was not significant. Myocardial 125I uptake at 15 min was significantly lower in the CD group than in the control group, even in the insulin-treated rats [control (CC), 4.4+/-0.4; not treated (CDN), 3.3+/-0.5; insulin-treated (CDI), 3.4+/-0.4 x 10(4) cpm/g, p<0.05 in each case]. The 125I count value corrected for the blood count (counts/min (cpm) per g of protein divided by blood cpm) in the MF decreased by 40% at 60 min in the CC group, but increased by 60% in the CDN group. The results of the present study suggest that the myocardial uptake of branched-chain fatty acids is decreased in rats with chronic diabetes, probably as a result of mitochondrial dysfunction.
Shinmura
K
K
Department of Geriatric Medicine, Keio University School of Medicine, Tokyo, Japan.
Tani
M
M
Suganuma
Y
Y
Hasegawa
H
H
Hayashi
Y
Y
Guo
X D
XD
Nakamura
Y
Y
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000097:blood / Q000493:pharmacokinetics*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008055:Lipids; C049338:iodofiltic acid