TY - JOUR
T1 - Quantification of the relative impairment in actions of insulin on hepatic glucose production and peripheral glucose uptake in non-insulin-dependent diabetes mellitus
AU - Campbell, Peter J.
AU - Mandarino, Lawrence J.
AU - Gerich, John E.
N1 - Funding Information:
From the Division of Endocrinology, Department of Medicine. Vanderbilt School of Medicine, Nashville, TN: the Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine; and the Clinical Research Center and Diabetes Section, Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, University of Pittsburgh School of Medicine. Supported by the USPHS (AM-20411. AM-07352. RR-00585) and ihe Mayo Foundation. Address reprint requests to John E. Gerich. MD, University of Piftsburgh, Clinical Research Center, 3488 Presbyterian-University Hospital, 230 Lothrop St, Pittsburgh, PA 15261. o 1988 by Grune & Stratton, Inc. 0026-0495/88/3701-0004$03.00/O
PY - 1988/1
Y1 - 1988/1
N2 - In non-insulin-dependent diabetes mellitus (NIDDM), both liver and peripheral tissues are resistant to insulin, but the relative severity and contribution of these abnormalities to fasting hyperglycemia are poorly understood. We, therefore, determined the dose-response characteristics for insulin-mediated suppression of hepatic glucose production (GP) and stimulation of peripheral glucose uptake (GU) in 14 NIDDM subjects and 14 age- and weight-matched nondiabetic volunteers (NV) using the glucose clamp sequential insulin infusion technique along with isotopic estimation of glucose flux. Postabsorptive rates of both GP (94 ± 7 v 72 ± 2 mg/M2/min in NV, P < .01) and GU (88 ± 5 v 72 ± 2 in NV, P < .01) were significantly increased in NIDDM subjects. The ED50 (half-maximally effective plasma insulin concentration) in NIDDM subjects for suppression of GP (64 ± 14 μU/mL) and stimulation of GU (118 ± 20 μU/mL were both increased more than twofold above normal (26 ± 2 and 58 ± 5 μU/mL, respectively, both P < .01) and were significantly correlated with one another (r = .68, P < .01). Although GP could be totally suppressed in the NIDDM subjects, their maximal GU was reduced 30% (287 ± 20 v 372 ± 15 mg/m2/min in NV, P < .01). Nevertheless, at all physiologically relevant plasma insulin concentrations studied, there was comparable impairment in GP and GU responses. Moreover, fasting plasma glucose concentrations in NIDDM subjects were highly correlated with their increased basal rates of GP (r = .81, P < .005) but not with their reduced GU. We conclude that hepatic and peripheral tissues are equally resistant to insulin in NIDDM. Because insulin exerts an appreciable suppressive effect on hepatic GP in the postabsorptive state when only 20% to 30% of GU is insulin-mediated, our findings suggest that hepatic, rather than peripheral, insulin resistance is the major factor responsible for fasting hyperglycemia in this disorder.
AB - In non-insulin-dependent diabetes mellitus (NIDDM), both liver and peripheral tissues are resistant to insulin, but the relative severity and contribution of these abnormalities to fasting hyperglycemia are poorly understood. We, therefore, determined the dose-response characteristics for insulin-mediated suppression of hepatic glucose production (GP) and stimulation of peripheral glucose uptake (GU) in 14 NIDDM subjects and 14 age- and weight-matched nondiabetic volunteers (NV) using the glucose clamp sequential insulin infusion technique along with isotopic estimation of glucose flux. Postabsorptive rates of both GP (94 ± 7 v 72 ± 2 mg/M2/min in NV, P < .01) and GU (88 ± 5 v 72 ± 2 in NV, P < .01) were significantly increased in NIDDM subjects. The ED50 (half-maximally effective plasma insulin concentration) in NIDDM subjects for suppression of GP (64 ± 14 μU/mL) and stimulation of GU (118 ± 20 μU/mL were both increased more than twofold above normal (26 ± 2 and 58 ± 5 μU/mL, respectively, both P < .01) and were significantly correlated with one another (r = .68, P < .01). Although GP could be totally suppressed in the NIDDM subjects, their maximal GU was reduced 30% (287 ± 20 v 372 ± 15 mg/m2/min in NV, P < .01). Nevertheless, at all physiologically relevant plasma insulin concentrations studied, there was comparable impairment in GP and GU responses. Moreover, fasting plasma glucose concentrations in NIDDM subjects were highly correlated with their increased basal rates of GP (r = .81, P < .005) but not with their reduced GU. We conclude that hepatic and peripheral tissues are equally resistant to insulin in NIDDM. Because insulin exerts an appreciable suppressive effect on hepatic GP in the postabsorptive state when only 20% to 30% of GU is insulin-mediated, our findings suggest that hepatic, rather than peripheral, insulin resistance is the major factor responsible for fasting hyperglycemia in this disorder.
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U2 - 10.1016/0026-0495(88)90023-6
DO - 10.1016/0026-0495(88)90023-6
M3 - Article
C2 - 3275857
AN - SCOPUS:0023832956
SN - 0026-0495
VL - 37
SP - 15
EP - 21
JO - Metabolism
JF - Metabolism
IS - 1
ER -