Delayed transcapillary transport of insulin to muscle interstitial fluid in obese subjects.
Insulin-resistant subjects have a slow onset of insulin action, and the underlying mechanism has not been determined. To evaluate whether a delayed transcapillary transport is part of the peripheral insulin resistance, we followed the kinetics of infused insulin and inulin in plasma and muscle interstitial fluid in obese insulin-resistant patients and control subjects. A total of 10 lean and 10 obese men (BMI 24 +/- 0.8 vs. 32 +/- 0.8 kg/m(2), P < 0.001) was evaluated during a hyperinsulinemic-euglycemic clamp (insulin infusion rate 120 mU. m(-2). min(-1)) combined with an inulin infusion. Measurements of insulin and inulin in plasma were taken by means of arterial-venous catheterization of the forearm and microdialysis in brachioradialis muscle combined with forearm blood flow measurements with vein occlusion pletysmography. The obese subjects had a significantly lower steady-state glucose infusion rate and, moreover, demonstrated a delayed appearance of insulin (time to achieve half-maximal concentration [T(1/2)] 72 +/- 6 vs. 46 +/- 6 min in control subjects, P < 0.05) as well as inulin (T(1/2) 83 +/- 3 vs. 53 +/- 7 min, P < 0.01) in the interstitial fluid. Also, the obese subjects had a delayed onset of insulin action (T(1/2) 70 +/- 9 vs. 45 +/- 5 min in control subjects, P < 0.05), and their forearm blood flow rate was significantly lower. These results demonstrate a delayed transcapillary transport of insulin and inulin from plasma to the muscle interstitial fluid and a delayed onset of insulin action in insulin-resistant obese subjects.
Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg, Sweden. mikaela.sjostrand@medic.gu.se
Mikaela
M
Sjöstrand
Soffia
S
Gudbjörnsdottir
Agneta
A
Holmäng
Lars
L
Lönn
Lena
L
Strindberg
Peter
P
Lönnroth
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002196:Capillaries; D005110:Extracellular Space / Q000378:metabolism*; D005542:Forearm / Q000098:blood supply; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D007444:Inulin / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D012016:Reference Values; D012039:Regional Blood Flow; D013851:Thinness
D001786:Blood Glucose; D007328:Insulin; D007444:Inulin