The insulin-sensitizing effect of rosiglitazone in type 2 diabetes mellitus patients does not require improved in vivo muscle mitochondrial function.
OBJECTIVE
Our objective was to investigate whether improved in vivo mitochondrial function in skeletal muscle and intramyocellular lipids (IMCLs) contribute to the insulin-sensitizing effect of rosiglitazone.


METHODS
Eight overweight type 2 diabetic patients (body mass index = 29.3 +/- 1.1 kg/m(2)) were treated with rosiglitazone for 8 wk. Before and after treatment, insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp. Muscular mitochondrial function (half-time of phosphocreatine recovery after exercise) and IMCL content were measured by magnetic resonance spectroscopy.


RESULTS
Insulin sensitivity improved after rosiglitazone (glucose infusion rate: 19.9 +/- 2.8 to 24.8 +/- 2.1 micromol/kg.min; P < 0.05). In vivo mitochondrial function (phosphocreatine recovery half-time: 23.8 +/- 3.5 to 20.0 +/- 1.7 sec; P = 0.23) and IMCL content (0.93 +/- 0.18% to 1.37 +/- 0.40%; P = 0.34) did not change. Interestingly, the changes in PCr half-time correlated/tended to correlate with changes in fasting insulin (R(2) = 0.50; P = 0.05) and glucose (R(2) = 0.43; P = 0.08) levels. Changes in PCr half-time did not correlate with changes in glucose infusion rate (R(2) = 0.08; P = 0.49).


CONCLUSIONS
The rosiglitazone-enhanced insulin sensitivity does not require improved muscular mitochondrial function.
Schrauwen-Hinderling
Vera B
VB
Department of Radiology, Maastricht University Hospital, Maastricht, The Netherlands. v.schrauwen@hb.unimaas.nl
Mensink
Marco
M
Hesselink
Matthijs K C
MK
Sels
Jean-Pierre
JP
Kooi
M Eline
ME
Schrauwen
Patrick
P
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000502:physiology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone