Estimations of muscle interstitial insulin, glucose, and lactate in type 2 diabetic subjects.
Previous measurement of insulin in human muscle has shown that interstitial muscle insulin and glucose concentrations are approximately 30-50% lower than in plasma during hyperinsulinemia in normal subjects. The aims of this study were to measure interstitial muscle insulin and glucose in patients with type 2 diabetes to evaluate whether transcapillary transport is part of the peripheral insulin resistance. Ten patients with type 2 diabetes and ten healthy controls matched for sex, age, and body mass index were investigated. Plasma and interstitial insulin, glucose, and lactate (measured by intramuscular in situ-calibrated microdialysis) in the medial quadriceps femoris muscle were analyzed during a hyperinsulinemic euglycemic clamp. Blood flow in the contralateral calf was measured by vein plethysmography. At steady-state clamping, at 60-120 min, the interstitial insulin concentration was significantly lower than arterial insulin in both groups (409 +/- 86 vs. 1,071 +/- 99 pmol/l, P < 0.05, in controls and 584 +/- 165 vs. 1, 253 +/- 82 pmol/l, P < 0.05, in diabetic subjects, respectively). Interstitial insulin concentrations did not differ significantly between diabetic subjects and controls. Leg blood flow was significantly higher in controls (8.1 +/- 1.2 vs. 4.4 +/- 0.7 ml. 100 g(-1).min(-1) in diabetics, P < 0.05). Calculated glucose uptake was less in diabetic patients compared with controls (7.0 +/- 1.2 vs. 10.8 +/- 1.2 micromol. 100 g(-1).min(-1), P < 0.05, respectively). Arterial and interstitial lactate concentrations were both higher in the control group (1.7 +/- 0.1 vs. 1.2 +/- 0.1, P < 0. 01, and 1.8 +/- 0.1 vs. 1.2 +/- 0.2 mmol/l, P < 0.05, in controls and diabetics, respectively). We conclude that, during hyperinsulinemia, muscle interstitial insulin and glucose concentrations did not differ between patients with type 2 diabetes and healthy controls despite a significantly lower leg blood flow in diabetic subjects. It is suggested that decreased glucose uptake in type 2 diabetes is caused by insulin resistance at the cellular level rather than by a deficient access of insulin and glucose surrounding the muscle cell.
Sjöstrand
M
M
Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, S-413 45 Goteborg, Sweden. mikaela.sjostrand@medic.gu.se
Holmäng
A
A
Strindberg
L
L
Lönnroth
P
P
D000328:Adult; D001158:Arteries; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005110:Extracellular Space / Q000737:chemistry; D005260:Female; D005947:Glucose / Q000032:analysis*; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000032:analysis* / Q000097:blood; D007333:Insulin Resistance; D019344:Lactic Acid / Q000032:analysis* / Q000097:blood; D007866:Leg; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000737:chemistry*
D001786:Blood Glucose; D007328:Insulin; D019344:Lactic Acid; D005947:Glucose