Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans

Abstract

In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose effectiveness assessed under dynamic and steady state conditions. Comparability of uptake versus production components.

“…By defining this parameter as the change in R d for a given increment in glucose, at fixed basal insulin, this working definition can be applied to the most widely used clamp-based index of glucose action, non-insulin-mediated glucose uptake (41)(42)(43), defined as R d during somatostatin-induced insulinopenia. Baron and coworkers (41) report that in humans, when glucose was raised from 88 to 220 mg/dl at "zero" insulin in normal subjects, R d rose from 128 to 213 mg/min. Thus, clamp-based GE (uptake) ϭ 0.644 dl/min for non-insulin-mediated glucose uptake data obtained at zero insulin.…”

Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.

“…Subsequently, the right femoral artery and vein were cannulated. A 5 French sheath (Cordis Laboratories, Inc., Miami, FL) was placed in the right femoral vein to allow the insertion of a custom-designed 5 French double lumen thermodilution catheter (Baxter Scientific, Edwards Division, Irvine, CA) to measure leg blood flow (LBF) as previously described (8). The right femoral artery was cannulated with a 5.5 French double lumen catheter (Arrow International, Reading, PA) to allow simultaneous infusion of substances through the proximal (most caudad), and invasive blood pressure monitoring through the distal port (most cephalad).…”

Insulin resistance syndrome: possible key role of blood flow in resting muscle

“…For kinetic reasons, blood flow in muscles must be rate-limiting for their glucose uptake if a high insulin level is combined with a normal glucose level [5]. Glucose extraction of 20-30 % across the leg or forearm has been reported [6,7], but part of the venous blood came from tissues with low uptake. Therefore, we can assume that muscle uptake may have been as high as 40 %.…”