Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects.
OBJECTIVE
Recent studies suggest that insulin resistance is associated with increased intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) contents. While metformin improves insulin resistance mainly in liver, its effects on IHL and IMCL have not been clarified yet. The aim of this study was to investigate the effects of low-dose metformin (750 mg/day) on peripheral insulin sensitivity, IHL and IMCL.


METHODS
Before and 3 months after low-dose metformin therapy, eight overweight/obese Japanese subjects [body mass index (BMI) >25 kg/m2] were studied with blood sampling, measurement of IHL and IMCL by 1H magnetic resonance spectroscopy and glucose infusion rate (GIR) during euglycaemic-hyperinsulinaemic clamp as an index of peripheral insulin sensitivity.


RESULTS
A 3-month low-dose metformin therapy did not alter body weight, total body fat, fat distribution or physical activity level but increased GIR by 31% (from 6.24 +/- 0.86 to 7.82 +/- 0.82 mg/kg/min, p < 0.01). Although metformin treatment did not alter IMCL (from 4.1 +/- 1.0 to 4.2 +/- 0.9, not significant), it decreased IHL by 21% (from 15.9 +/- 2.8 to 11.8 +/- 2.2%, p < 0.05).


CONCLUSIONS
A 3-month low-dose metformin treatment improved peripheral insulin sensitivity and reduced IHL, without significantly changing BMI, adiposity or IMCL.
Tamura
Y
Y
Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan.
Watada
H
H
Sato
F
F
Kumashiro
N
N
Sakurai
Y
Y
Hirose
T
T
Tanaka
Y
Y
Kawamori
R
R
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects; D007564:Japan; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin