PMID- 19141588
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20221207
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 94
IP  - 4
DP  - 2009 Apr
TI  - Effect of hyperglycemia on mitochondrial respiration in type 2 diabetes.
PG  - 1372-8
LID - 10.1210/jc.2008-1475 [doi]
AB  - AIM: Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus 
      (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function 
      is unknown. This study examined the effect of different levels of glycemia on 
      skeletal muscle mitochondrial function in patients with T2DM. PATIENTS AND 
      METHODS: Eleven patients with T2DM [9 males, 2 females; age, 52.8 +/- 2.5 yr 
      (mean +/- se); body mass index, 30.2 +/- 1.1 kg/m(2)] in poor glycemic control 
      were treated with insulin aspart and NPH insulin for a median period of 46 d 
      (range, 31-59). Mitochondrial respiration and citrate synthase activity (a marker 
      of mitochondrial content) were measured before and after treatment. Eleven 
      healthy subjects (age, 53.3 +/- 2.7 yr; body mass index, 30.6 +/- 1.1 kg/m(2)) 
      were included as controls. RESULTS: Hemoglobin A1c (9.1 +/- 0.5 to 7.5 +/- 0.3%; 
      P < 0.001) and fasting plasma glucose (12.7 +/- 1.1 to 6.5 +/- 0.3 mmol/liter; P 
      < 0.001) were reduced after treatment. Mitochondrial respiration per milligram 
      muscle was lower in T2DM compared to controls [substrates for complex I, 24% 
      lower (P < 0.05); substrates for complex I+II, 17% lower (P < 0.05)]. 
      Mitochondrial respiration and citrate synthase activity did not differ before and 
      after improvements in glycemic control, but mitochondrial respiration correlated 
      with fasting plasma glucose before (r(2) = 0.53; P < 0.05) but not after 
      treatment [r(2) = 0.0024; not significant (NS)]. Mitochondrial respiration 
      normalized to mitochondrial content did not differ between control subjects and 
      patients with T2DM. DISCUSSION: Mitochondrial respiration and content was not 
      improved after significant improvements in glycemic control. However, severe 
      hyperglycemia inhibited respiration reversibly, but moderate hyperglycemia and 
      mitochondrial function were not correlated.
FAU - Rabol, Rasmus
AU  - Rabol R
AD  - Department of Biomedical Sciences, Faculty of Health Sciences, Copenhagen Muscle 
      Research Centre, University of Copenhagen, Copenhagen, Denmark. 
      rasmus.rabol@yale.edu
FAU - Hojberg, Patricia M V
AU  - Hojberg PM
FAU - Almdal, Thomas
AU  - Almdal T
FAU - Boushel, Robert
AU  - Boushel R
FAU - Haugaard, Steen B
AU  - Haugaard SB
FAU - Madsbad, Sten
AU  - Madsbad S
FAU - Dela, Flemming
AU  - Dela F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090113
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 4429-04-3 (Fructosamine)
RN  - 53027-39-7 (Insulin, Isophane)
RN  - D933668QVX (Insulin Aspart)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Glucose/drug effects/metabolism
MH  - Body Mass Index
MH  - Diabetes Mellitus, Type 2/blood/drug therapy/*metabolism
MH  - Female
MH  - Fructosamine/blood
MH  - Glycated Hemoglobin/drug effects/metabolism
MH  - Humans
MH  - Hyperglycemia/drug therapy/*metabolism
MH  - Hypoglycemic Agents/therapeutic use
MH  - Insulin/analogs & derivatives/therapeutic use
MH  - Insulin Aspart
MH  - Insulin, Isophane/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Mitochondria, Muscle/*metabolism
MH  - Muscle, Skeletal/metabolism
MH  - Oxygen Consumption/drug effects/*physiology
EDAT- 2009/01/15 09:00
MHDA- 2009/05/15 09:00
CRDT- 2009/01/15 09:00
PHST- 2009/01/15 09:00 [entrez]
PHST- 2009/01/15 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
AID - jc.2008-1475 [pii]
AID - 10.1210/jc.2008-1475 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2009 Apr;94(4):1372-8. doi: 10.1210/jc.2008-1475. Epub 
      2009 Jan 13.