Journal
DIABETES
Volume 56, Issue 12, Pages 2958-2963Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db07-0670
Keywords
-
Categories
Funding
- NCRR NIH HHS [RR-00847] Funding Source: Medline
- NIDDK NIH HHS [DK-063609, DK-073759, DK-057878] Funding Source: Medline
Ask authors/readers for more resources
OBJECTIVE- Transport of insulin from the central circulation into muscle is rate limiting for the stimulation of glucose metabolism. By recruiting muscle microvasculature, insulin may promote its own movement into muscle interstitium. We tested whether in humans, as in the rat, insulin exerts an early action to recruit microvasculature within skeletal muscle. We further hypothesized that expansion of the microvascular volume of muscle would enhance muscle insulin clearance. RESEARCH DESIGN AND METHODS- Microvascular volume, total blood flow, and muscle insulin and glucose uptake (forearm balance method) were measured in 14 lean, healthy volunteers before and during a 2-h hyperinsulinemic-euglycemic clamp (1 mU center dot kg(-1) center dot min(-1)). Microvascular volume was measured using contrast-enhanced ultrasound. RESULTS- Forearm muscle microvascular volume increased within 20 min of insulin infusion (P < 0.01), whereas an effect to increase total forearm flow was not observed until 100 min. Forearm insulin uptake increased with physiological hypeninsulinemia (15 +/- 3 and 87 +/- 13 fmol center dot min(-1) center dot 100 ml(-1) basal vs. last 40 min of clamp, P < 0.001). However, the extraction fraction and clearance of insulin declined (P = 0.02, for each), indicating saturability of muscle insulin uptake at physiological hyperinsulinemia. CONCLUSIONS- Skeletal muscle contributes to peripheral insulin clearance both in the basal state and with physiological hyperinsulinemia. Insulin promptly expands human muscle microvascular volume but only slowly increases blood flow. Despite increased microvascular volume available for insulin uptake, muscle insulin clearance decreases significantly. These findings are consistent with the presence of a saturable transport mechanism facilitating the transendothelial transport of insulin into human muscle.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available