Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM.
Patients with non-insulin-dependent diabetes mellitus (NIDDM) exhibit decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Because IMGU is equal to the product of the arteriovenous glucose difference (AVG delta) across and blood flow (F) into muscle (IMGU = AVG delta x F), reduced tissue permeability (AVG delta) and/or glucose and insulin delivery (F) can potentially lead to decreased IMGU. The components of skeletal muscle IMGU were studied in six obese NIDDM subjects (103 +/- 9 kg) and compared with those previously determined in six lean (weight 68 +/- 3 kg), and six obese (94 +/- 3 kg) with normal glucose tolerance. The insulin dose-response curves for whole body and leg muscle IMGU were constructed using the combined euglycemic clamp and leg balance techniques during sequential insulin infusions (range of serum insulin 130-80,000 pmol/L). In lean, obese, and NIDDM subjects, whole body IMGU, femoral AVG delta, and leg IMGU increased in a dose-dependent fashion over the range of insulin with an ED50 of 400-500 pmol/L in lean, 1000-1200 pmol/L in obese, and 4000-7000 pmol/L in NIDDM subjects (P less than 0.01 lean vs. obese and NIDDM). In lean and obese subjects, maximally effective insulin concentrations increased leg blood flow approximately 2-fold from basal with an ED50 of 266 pmol/L and 957 pmol/L, respectively (P less than 0.01 lean vs. obese). In contrast, leg F did not increase from the basal value in NIDDM subjects (2.7 +/- 0.1 vs. 3.5 +/- 0.5 dl/min, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Laakso
M
M
Department of Medicine, Indian University School of Medicine, Indianapolis.
Edelman
S V
SV
Brechtel
G
G
Baron
A D
AD
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007866:Leg / Q000098:blood supply; D009132:Muscles / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose