PMID- 26732686
OWN - NLM
STAT- MEDLINE
DCOM- 20160802
LR  - 20220316
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 310
IP  - 6
DP  - 2016 Mar 15
TI  - Assessment of myocardial metabolic flexibility and work efficiency in human type 
      2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.
PG  - E452-60
LID - 10.1152/ajpendo.00437.2015 [doi]
AB  - Altered myocardial fuel selection likely underlies cardiac disease risk in 
      diabetes, affecting oxygen demand and myocardial metabolic flexibility. We 
      investigated myocardial fuel selection and metabolic flexibility in human type 2 
      diabetes mellitus (T2DM), using positron emission tomography to measure rates of 
      myocardial fatty acid oxidation 16-[(18)F]fluoro-4-thia-palmitate (FTP) and 
      myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent 
      paired studies under fasting conditions, comparing 3-h insulin + glucose 
      euglycemic clamp conditions (120 mU.m(-2).min(-1)) to 3-h saline infusion. Lean 
      controls (n = 10) were compared with glycemically controlled volunteers with T2DM 
      (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both 
      groups (all P < 0.01) and significantly increased myocardial oxygen consumption 
      (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available 
      nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher 
      in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty 
      acid oxidation was seen in both groups (P < 0.0001). However, fatty acid 
      oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial 
      work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with 
      the insulin-induced increase in work and shift in fuel utilization (P = 0.01). 
      Augmented fatty acid oxidation is present under baseline and insulin-treated 
      conditions in T2DM, with impaired insulin-induced shifts away from fatty acid 
      oxidation. This is accompanied by reduced work efficiency, possibly due to 
      greater oxygen consumption with fatty acid metabolism. These observations suggest 
      that improved fatty acid suppression, or reductions in myocardial fatty acid 
      uptake and retention, could be therapeutic targets to improve myocardial ischemia 
      tolerance in T2DM.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Mather, K J
AU  - Mather KJ
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and kmather@iu.edu.
FAU - Hutchins, G D
AU  - Hutchins GD
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and.
FAU - Perry, K
AU  - Perry K
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and.
FAU - Territo, W
AU  - Territo W
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and.
FAU - Chisholm, R
AU  - Chisholm R
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and.
FAU - Acton, A
AU  - Acton A
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and.
FAU - Glick-Wilson, B
AU  - Glick-Wilson B
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and.
FAU - Considine, R V
AU  - Considine RV
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and.
FAU - Moberly, S
AU  - Moberly S
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and.
FAU - DeGrado, T R
AU  - DeGrado TR
AD  - Indiana University School of Medicine, Indianapolis, Indiana; and Mayo Clinic, 
      Rochester, Minnesota.
LA  - eng
GR  - TR000006/TR/NCATS NIH HHS/United States
GR  - M01-RR00750/RR/NCRR NIH HHS/United States
GR  - R01 HL117620/HL/NHLBI NIH HHS/United States
GR  - UL1 TR000006/TR/NCATS NIH HHS/United States
GR  - UL1 TR001108/TR/NCATS NIH HHS/United States
GR  - P30 DK097512/DK/NIDDK NIH HHS/United States
GR  - R21-DK-071142/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160105
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (16-fluoro-4-thiapalmitic acid)
RN  - 0 (Fatty Acids)
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Insulin)
RN  - 0 (Palmitates)
RN  - 0 (Thiones)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/diagnostic imaging/*metabolism
MH  - Efficiency
MH  - Fatty Acids/*metabolism
MH  - Female
MH  - Fluorine Radioisotopes
MH  - Glucose/*metabolism
MH  - Glucose Clamp Technique
MH  - Heart/*diagnostic imaging/drug effects
MH  - Humans
MH  - Insulin/pharmacology
MH  - Lipid Metabolism/drug effects/*physiology
MH  - Male
MH  - Middle Aged
MH  - Myocardium/*metabolism
MH  - Oxidation-Reduction/drug effects
MH  - Oxygen Consumption/drug effects/*physiology
MH  - Palmitates
MH  - Positron-Emission Tomography
MH  - Thiones
PMC - PMC4796267
OTO - NOTNLM
OT  - diabetes
OT  - heart
OT  - metabolic flexibility
OT  - metabolism
OT  - myocardial
OT  - positron emission tomography
EDAT- 2016/01/07 06:00
MHDA- 2016/08/03 06:00
PMCR- 2017/03/15
CRDT- 2016/01/07 06:00
PHST- 2015/10/05 00:00 [received]
PHST- 2015/12/19 00:00 [accepted]
PHST- 2016/01/07 06:00 [entrez]
PHST- 2016/01/07 06:00 [pubmed]
PHST- 2016/08/03 06:00 [medline]
PHST- 2017/03/15 00:00 [pmc-release]
AID - ajpendo.00437.2015 [pii]
AID - E-00437-2015 [pii]
AID - 10.1152/ajpendo.00437.2015 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2016 Mar 15;310(6):E452-60. doi: 
      10.1152/ajpendo.00437.2015. Epub 2016 Jan 5.