Glucose Uptake In Humans Research Articles

Kinetics of Insulin-Mediated and Non-Insulin-Mediated Glucose Uptake in Humans

The kinetics of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU) in humans have not been well defined. We used the glucose-clamp technique to measure rates of whole-body and leg muscle glucose uptake in six healthy lean men during hyperinsulinemia (approximately 460 pM) to study IMGU and during somatostatin-induced insulinopenia to study NIMGU at four glucose levels (4.5, 9, 12, and 21 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference [A-VG] x blood flow). With this approach, we found that, during hyperinsulinemia, both whole-body and leg glucose uptake increased in a curvilinear fashion at every glucose level, the highest glucose uptake values obtained being 139 +/- 17 mumol.kg-1.min-1 and 3656 +/- 931 mumol.min-1.leg-1, respectively. Leg blood flow increased twofold from 6.0 +/- 1.7 to 11.7 +/- 3.1 dl/min (P less than 0.01) over the range of glucose and was correlated with whole-body glucose uptake (r = 0.55, P less than 0.005). Leg muscle glucose extraction, independent of changes in blood flow, which is reflected by the A-VG, saturated over the range of glucose (1.28 +/- 0.12, 2.22 +/- 0.30, 2.92 +/- 0.42, 3.02 +/- 0.41 mM, NS between last 2 values) with a half-maximal effective glucose concentration (EG50) of 5.3 +/- 0.4 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics of insulin-mediated and non-insulin-mediated glucose uptake in humans

Kinetics of insulin-mediated and non-insulin-mediated glucose uptake in humans

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

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)

Effect of physical exercise on sensitivity and responsiveness to insulin in humans.

The effect of acute physical exercise on insulin sensitivity and responsiveness of glucose uptake and hepatic glucose production was studied. Seven untrained men were subjected to four sequential euglycemic hyperinsulinemic clamps after rest (R), immediately after exercise (E), as well as 48 h after 60 min of 150 W ergometer exercise (ER). Insulin-mediated glucose uptake was higher on E and ER days compared with R days. Apparent Km decreased after exercise (52 +/- 3 R vs. 43 +/- 4 E and 40 +/- 3 ER microU/ml, means +/- SE) and Vmax increased (9.5 +/- 0.8 R vs. 10.9 +/- 0.7 E and 10.7 +/- 0.8 ER mg.min-1.kg-1). Glucose oxidation increased with the increasing insulin infusion rate, and maximal glucose oxidation rate was lower on E days compared with R days. The maximal conversion rate of glucose to glycogen was higher on E and ER days (8.0 +/- 0.3 and 7.2 +/- 0.2, respectively) than on R days (5.7 +/- 0.6 mg.min-1 kg-1). Muscle glycogen synthase I activity was higher immediately after exercise and remained higher for the next 48 h. No change in any glucoregulatory hormone or metabolite could explain the increased insulin action seen after exercise. In additional experiments (n = 3), no remaining effect existed 5 days after exercise. Both insulin and exercise suppressed the pancreatic secretion of insulin and proinsulin. The conclusions drawn are that prolonged moderate exercise increases insulin action on glucose uptake in humans by reducing apparent Km and increasing Vmax. This effect lasts 48 h but not 5 days. The increased insulin action may be related to an exercise-induced increase in glycogen synthase activity.

Somatostatin does not increase insulin-stimulated glucose uptake in humans.

Somatostatin (SRIF) has been widely used in the study of in vivo carbohydrate metabolism to suppress pancreatic hormone secretion and thereby interrupt the glucoregulatory feedback loops between insulin, glucagon, and glucose. A critical assumption in the use of SRIF is that it has no effect on hepatic or peripheral glucose metabolism other than those mediated through the inhibition of hormone secretion. To assess whether doses of SRIF commonly used in human investigation have any effect on insulin-stimulated glucose disposal rates, we measured the rate in 6 normal subjects (mean fasting serum glucose level, 93 +/- 2 mg/dl) during euglycemic (approximately equal to 85 mg/dl) hyperinsulinemic (40 mU X m-2 X min-1) clamp studies both with and without the concomitant infusion of SRIF (600 micrograms/hr). The steady-state insulin levels achieved were 85 +/- 6 microU/ml and 74 +/- 8 microU/ml with and without SRIF, respectively (difference not significant). Glucose disposal rates between 120 and 180 min of the clamp were 7.11 +/- 0.10 and 7.35 +/- 0.10 mg X kg-1 X min-1 with and without SRIF, respectively (difference not significant). We concluded that in doses commonly used in human investigation, SRIF does not increase glucose disposal.

Somatostatin does not increase insulin-stimulated glucose uptake in humans

Somatostatin does not increase insulin-stimulated glucose uptake in humans