TY - JOUR
T1 - Rates of noninsulin-mediated glucose uptake are elevated in Type II diabetic subjects
AU - Baron, A. D.
AU - Kolterman, O. G.
AU - Bell, J.
AU - Mandarino, L. J.
AU - Olefsky, J. M.
PY - 1985
Y1 - 1985
N2 - Although insulin is extremely potent in regulating glucose transport in insulin-sensitive tissues, all tissues are capable of taking up glucose by facilitated diffusion by means of a noninsulin-mediated glucose uptake (NIMGU) system. Several reports have estimated that in the postabsorptive state the majority of glucose disposal occurs via a NIMGU mechanism. However, these estimates have been either derived or extrapolated in normal humans. In the present study we have directly measured NIMGU rates in 11 normal (C) and 7 Type II noninsulin-dependent diabetic subjects (NIDDM; mean±SE fasting serum glucose, 249±24 mg/dl). To accomplish this, the serum glucose was clamped at a desired level during a period of insulin deficiency induced by a somatostatin infusion (SRIF, 550 μg/h). With a concomitant [3-3H]glucose infusion, we could isotopically quantitate glucose disposal rates (R(d)) during basal (basal insulin present) and insulin-deficient (SRIF) conditions. With this approach we found that (a) basal R(d) was greater in NIDDM than in C, 274±31 vs. 150±7 mg/min, due to elevated hepatic glucose output, (b) NIMGU composes 75±5% of basal R(d) in C and 71±4% in NIDDM, (c) NIDDMS have absolute basal NIMGU rates that are twice that of C (195±23 vs. 113±8 mg/min, P < 0.05), (d) when C were studied under conditions of insulin deficiency (SRIF infusion) and at a serum glucose level comparable to that of the NIDDM group (250 mg/dl), their rates of NIMGU were the same as that of the NIDDM group (186±19 vs. 195±23 mg/min; NS). We conclude that (a) in the postabsorptive state, NIMGU is the major pathway for glucose disposal for both C and NIDDM; (b) for a given glucose level the efficiency of NIMGU (NIMGU divided by serum glucose level) is equal in C and NIDDM, but since basal R(d) is elevated in NIDDMs their absolute basal rates of NIMGU are higher; and (c) elevated basal rates of NIMGU in NIDDM may play a role in the pathogenesis of the late complications of diabetes.
AB - Although insulin is extremely potent in regulating glucose transport in insulin-sensitive tissues, all tissues are capable of taking up glucose by facilitated diffusion by means of a noninsulin-mediated glucose uptake (NIMGU) system. Several reports have estimated that in the postabsorptive state the majority of glucose disposal occurs via a NIMGU mechanism. However, these estimates have been either derived or extrapolated in normal humans. In the present study we have directly measured NIMGU rates in 11 normal (C) and 7 Type II noninsulin-dependent diabetic subjects (NIDDM; mean±SE fasting serum glucose, 249±24 mg/dl). To accomplish this, the serum glucose was clamped at a desired level during a period of insulin deficiency induced by a somatostatin infusion (SRIF, 550 μg/h). With a concomitant [3-3H]glucose infusion, we could isotopically quantitate glucose disposal rates (R(d)) during basal (basal insulin present) and insulin-deficient (SRIF) conditions. With this approach we found that (a) basal R(d) was greater in NIDDM than in C, 274±31 vs. 150±7 mg/min, due to elevated hepatic glucose output, (b) NIMGU composes 75±5% of basal R(d) in C and 71±4% in NIDDM, (c) NIDDMS have absolute basal NIMGU rates that are twice that of C (195±23 vs. 113±8 mg/min, P < 0.05), (d) when C were studied under conditions of insulin deficiency (SRIF infusion) and at a serum glucose level comparable to that of the NIDDM group (250 mg/dl), their rates of NIMGU were the same as that of the NIDDM group (186±19 vs. 195±23 mg/min; NS). We conclude that (a) in the postabsorptive state, NIMGU is the major pathway for glucose disposal for both C and NIDDM; (b) for a given glucose level the efficiency of NIMGU (NIMGU divided by serum glucose level) is equal in C and NIDDM, but since basal R(d) is elevated in NIDDMs their absolute basal rates of NIMGU are higher; and (c) elevated basal rates of NIMGU in NIDDM may play a role in the pathogenesis of the late complications of diabetes.
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U2 - 10.1172/JCI112169
DO - 10.1172/JCI112169
M3 - Article
AN - SCOPUS:0022387842
SN - 0021-9738
VL - 76
SP - 1782
EP - 1788
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 5
ER -