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1.
A modified minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in insulin-dependent diabetes 总被引:2,自引:0,他引:2
G M Ward K M Weber I M Walters P M Aitken B Lee J D Best R C Boston F P Alford 《Metabolism: clinical and experimental》1991,40(1):4-9
Although glucose utilization is impaired in insulin-dependent diabetes mellitus (IDDM), it is unclear whether this is due to reductions in insulin sensitivity (Si) and/or glucose-mediated glucose disposal (SG). The minimal model of Bergman et al can be applied to a frequently sampled intravenous glucose tolerance test (FSIGT) to simultaneously estimate Sl and SG, but cannot accommodate data from diabetics. Exogenous insulin approximating the normal pattern of insulin secretion was infused during FSIGTs in eight young non-obese C-peptide-negative IDDM subjects, but with the total dose modified to achieve sufficient glucose disappearance rates (KG) to allow analysis of data. The minimal model was modified to model the effects of the exogenous insulin on glucose kinetics to estimate SI and SG. Despite deliberately achieving supranormal plasma-free insulin levels during the FSIGT ("first-phase insulin" = 62 +/- 9 SE mU/L; "second phase insulin" = 34 +/- 9 mU/L), the diabetics showed low-normal KG values (1.3 +/- 0.29 min-1 X 10(2). Using the model, good parameter resolution (fractional SD [FSD] less than .5) was achieved (IDDM v controls: SI = 2.5 +/- 0.6 v 8.3 +/- 1.5 min-1.mU-1.L-1 X 10(4); SG = 1.6 +/- 0.5 v 2.6 +/- 0.2 min-1 X 10(2); P less than .05). This reduction in SG was confirmed in the same IDDM subjects by FSIGT during basal insulin infusion only (SG = 1.0 +/- 0.3 min-1 X 10(2)).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
2.
P. Tessari S. Inchiostro G. Biolo E. Duner R. Nosadini A. Tiengo G. Crepaldi 《Diabetologia》1985,28(11):870-872
Summary To determine whether hyperaminoacidaemia may modify insulin-mediated glucose disposal, normal subjects were studied with the euglycaemic glucose-clamp technique, with or without an amino acid infusion, at a rate sufficient to duplicate the plasma concentration of most amino acids. Steady-state glucose infusion rates to maintain euglycaemia were 36% lower during hyperaminoacidaemia (7.3±1.0 versus 11.4±0.8mg· kg–1· min–1, p<0.01) at comparable insulin concentrations (92±6 versus 93±7 mU/l respectively). Thus, under conditions of hyperinsulinaemia, amino acids could compete with glucose as metabolic fuels. 相似文献
3.
G S Meneilly D Elahi K L Minaker J W Rowe 《The Journal of clinical endocrinology and metabolism》1988,67(2):407-410
Somatostatin (SRIH) infusion has been widely used in metabolic studies of carbohydrate metabolism. While the effects of SRIH itself on various aspects of carbohydrate economy have been assessed in young adults, such studies have not been conducted in the elderly, which represent an increasingly important study group. To examine the effect of SRIH on insulin-mediated glucose disposal in the elderly, we studied 12 (7 men and 5 women) healthy nonobese subjects, aged 65-80 yr. Paired 3-h euglycemic insulin clamp studies were performed in random order employing insulin alone (22 mU/m2.min) or insulin with SRIH (250 micrograms/h) and glucagon (0.4 ng/kg.min) to maintain normal basal plasma glucagon levels. Basal plasma insulin, glucose, glucagon, GH, and glucose production and disappearance were similar on each occasion. Steady state (10-180 min) mean plasma insulin [insulin alone, 298 +/- 12 (+/- SE); insulin; glucagon, and SRIH, 304 +/- 15 pmol/L] and glucagon (insulin alone, 85 +/- 7; insulin, glucagon, and SRIH, 96 +/- 9 ng/L) concentrations were similar. At steady state (150-180 min) glucose production was suppressed to similar levels (insulin alone, 26 +/- 7; insulin, glucagon, and SRIH, 36 +/- 13 mumol/kg.min). However, steady state glucose disposal was significantly higher during the SRIH infusion (insulin alone, 295 +/- 26; insulin, glucagon, and SRIH, 346 +/- 32 mumol/kg.min; P less than 0.02). We conclude that SRIH augments insulin-mediated glucose disposal in healthy older subjects at physiological levels of insulin. 相似文献
4.
F Facchini M H Humphreys J Jeppesen G M Reaven 《The Journal of clinical endocrinology and metabolism》1999,84(5):1567-1569
To evaluate the stability of insulin-mediated glucose disposal, over time, we measured the steady-state plasma insulin (SSPI) and steady-state plasma glucose (SSPG) concentrations in response to a continuous infusion of SRIF (5 microg/min), insulin (25 microU/m2 x min), and dextrose (240 microg/m2 x min). These measurements were made in 15 healthy volunteers, studied before and after a mean (+/-SEM) interval of 48 +/- 2 months. The mean (+/-SEM) weight of the volunteers did not increase with time (75.4 +/- 3.1 vs. 76.6 +/- 3.2 kg), and there was no significant variation between the 2 mean (+/-SEM) values of either SSPI (324 +/- 18 vs. 372 +/- 24 pmol/L) or SSPG (8.4 +/- 1.0 vs. 8.2 +/- 1.0 mmol/L). Given the similarity of both SSPI and SSPG concentrations at baseline and follow-up, it can be concluded that insulin-mediated glucose disposal was stable in these 15 individuals over an interval of approximately 4 yr. 相似文献
5.
Dr. K. Osei D. A. Cottrell M. L. Henry R. J. Tesi R. M. Ferguson T. M. O'Dorisio 《Diabetologia》1992,35(7):676-680
Summary Decreased insulin sensitivity and glucose-dependent glucose disposal (glucose effectiveness) have been demonstrated in poorly-controlled Type 1 (insulin-dependent) diabetic patients. We have therefore examined the effects of successful pancreas transplantation that results in long-term physiologic normoglycaemia as measured by insulin sensitivity index and glucose effectiveness in 14 Type 1 diabetic recipients (Group 1) using the Bergman minimal model method. Their results were compared with those of five non-diabetic patients with kidney transplant alone (Group 2) and 10 healthy control subjects (Group 3). Mean plasma glucose levels were indistinguishable in Group 1 when compared to Groups 2 and 3. However, mean basal plasma insulin levels were two-and eight-fold greater in Group 1 (36±6 U/ml) than in Group 2 (17±7 U/ml) and Group 3 (4.5±0.6 U/ml), respectively. Following intravenous glucose (t=0 min) and tolbutamide (t=20), peak incremental insulin levels were significantly (p<0.001) greater in Group 1 vs Groups 2 and 3. Mean insulin sensitivity index was 65% and 50% lower in Group 1 (2.89±0.45) and Group 2 (4.11±1.30), respectively, when compared to GroupS (8.40±1.24×10–1 min–1 (U/ml)–1. In contrast, glucose effectiveness was similar in the three groups (Group 1, 2.48±0.26; Group 2, 2.05±0.21; and Group 3, 2.10±0.17×10–2·min–1). We conclude that, despite prednisone-induced insulin resistance, normal glucose tolerance is achieved by hyperinsulinaemia and normalisation of glucose-dependent glucose disposal following pancreas-kidney transplantation in Type 1 diabetic patients. 相似文献
6.
Lack of effect of sodium nitroprusside on insulin-mediated blood flow and glucose disposal in the elderly 总被引:1,自引:0,他引:1
Insulin increases skeletal muscle blood flow in healthy young subjects by a nitric oxide (NO)-dependent mechanism. Impairment of this mechanism may contribute to the insulin resistance of normal aging, a state characterized by reduced endothelial production of NO, an attenuated effect of insulin on skeletal muscle blood flow, and resistance to insulin-mediated glucose uptake (IMGU). We tested the hypothesis that the NO donor sodium nitroprusside (SNP) would augment insulin-mediated vasodilation and thus increase IMGU in healthy elderly subjects. Experiments were performed with young (n = 9; age, 25 +/- 1 years; body mass index [BMI], 24 +/- 1 kg/m2) and old (n = 10; age, 78 +/- 2 years; BMI, 25 +/- 1 kg/m2) healthy subjects. Each group underwent two studies in random order. In one study (control), insulin was infused using the euglycemic clamp protocol for 240 minutes at a rate of 40 mU/m2/min (young) and 34 mU/m2/min (old). In the other study (SNP), SNP was coinfused with insulin from 120 to 240 minutes. At regular intervals in each study, blood samples were obtained and calf blood flow was measured using venous occlusion plethysmography. Glucose and insulin values were similar in control and SNP studies in both age groups. In the young, SNP had no effect on blood flow to the calf, but its action in calf resistance vessels augmented insulin-mediated vasodilation, since incremental calf vascular conductance was greater during SNP infusion (control v SNP, 0.027 +/- 0.002 v 0.040 +/- 0.008 mL/100 mL/min/mm Hg, P< .0001). However, SNP had no effect on insulin-mediated glucose disposal. In the elderly, SNP reduced the blood flow to the calf, but this was countered by its effect on calf resistance vessels such that vascular conductance was unaffected (control v SNP, 0.012 +/- 0.003 v 0.011 +/- 0.003 mL/100 mL/min/mm Hg, P = nonsignificant [NS]). Steady-state (180 to 240 minutes) glucose disposal (control v SNP, 7.47 +/- 0.47 v 6.54 +/- 0.56 mg/kg/min, P < .01) rates were significantly lower during SNP infusion. In summary, systemic infusion of SNP did not increase insulin-mediated glucose disposal in either young or old subjects. Thus, the present findings do not support the concept that increasing NO availability will enhance glucose disposal in either age group. However, because the incremental increases in IMGU during SNP infusion paralleled the changes in blood supply to the calf rather than calf vascular conductance, any potential benefits on NO delivery in elderly subjects may have been offset by the direct or reflex effects of systemic hypotension. Other stimuli to NO production that do not cause hypotension must be tested before this therapeutic strategy can be considered as a potential means for enhancing the metabolic actions of insulin in the elderly. 相似文献
7.
C. Catalano P. H. Winocour T. H. Thomas M. Walker C. F. Sum R. Wilkinson K. G. M. M. Alberti 《Diabetologia》1993,36(1):52-56
Summary Insulin resistance in Type 1 (insulin-dependent) diabetes mellitus may be associated with raised erythrocyte sodium-lithium countertransport activity in patients with hypertension, or nephropathy, or both. However, in these circumstances it is difficult to separate the impact of hypertension, hyperlipidaemia and nephropathy on erythrocyte sodium-lithium countertransport from that of insulin resistance. We have therefore examined the relationship between insulin-mediated glucose disposal and erythrocyte sodiumlithium countertransport in 41 normotensive (mean blood pressure 120/74 mm Hg), normoalbuminuric (mean albumin excretion 6.2 g/min), normolipidaemic (mean serum cholesterol 4.3 mmol/l and mean serum triglycerides 1.0 mmol/l) Type 1 diabetic patients. Erythrocyte sodium-lithium countertransport was on average 0.31 mmol Li · h–1 · l erythrocytes –1 (range 0.07–0.69). Nine patients had values above 0.40 mmol Li · h–1 erythrocytes–1 (0.51±0.10 mmol Li · h–1 · l erythrocytes–1). The patients with high erythrocyte sodium-lithium countertransport were matched for age, sex, BMI, HbA1 and duration of diabetes, with nine patients with normal erythrocyte sodium-lithium countertransport. Insulin-mediated glucose disposal was evaluated during the last hour of a euglycaemic clamp (insulin 0.015 U · kg–1 · h–1; blood glucose clamped at 7.0 mmol/l). The free insulin levels were comparable between the patients with high and normal erythrocyte sodium-lithium countertransport (37.2±14.7 mU/l and 34.7±17.2 mU/l respectively). Insulin-mediated glucose disposal was on average 3.1±1.5 (range 0.8–6.8) mg · kg–1 · min–1. Erythrocyte sodium-lithium countertransport did not correlate with insulin-mediated glucose disposal in all 41 cases (r
s=–0.14), but when the matched groups were compared, patients with raised erythrocyte sodium-lithium countertransport had lower insulin-mediated glucose disposal rates compared to those with normal erythrocyte sodium-lithium countertransport (2.7±1.1 vs 3.9±1.3 mg · kg–1 · min–1; p=0.044). In these 18 patients a significant inverse relationship was found between erythrocyte sodium-lithium countertransport and insulin-mediated glucose disposal (r
s=–0.62; p=0.003). Raised erythrocyte sodium-lithium countertransport appears to be associated with insulin insensitivity in Type 1 diabetes, even in the absence of hyperlipidaemia, hypertension and nephropathy. 相似文献
8.
In vivo regulation of non-insulin-mediated and insulin-mediated glucose uptake by epinephrine 总被引:2,自引:0,他引:2
A D Baron P Wallace J M Olefsky 《The Journal of clinical endocrinology and metabolism》1987,64(5):889-895
In vivo glucose uptake (Rd) occurs via two mechanisms: 1) insulin-mediated glucose uptake (IMGU), which occurs in insulin-sensitive tissues, and 2) noninsulin-mediated glucose uptake (NIMGU), which occurs in both insulin-sensitive and insulin-insensitive tissues. Thus, in the postabsorptive (basal) state Rd = IMGU + NIMGU. To determine whether these two pathways for in vivo glucose disposal are regulated independently, we studied the effect of stress levels of epinephrine (EPI) on IMGU and NIMGU in seven normal men after an overnight fast. To study NIMGU, somatostatin (600 micrograms/hr) was infused to suppress endogenous insulin secretion, and glucose turnover was measured isotopically while the serum glucose level was clamped at about 200 mg/dL for 240 min. Separate studies were done during the infusion of saline or EPI (0.2 microgram/kg X min). The final 120 min of each study were used for data analysis. Under these conditions insulin action is absent and Rd = NIMGU. NIMGU was 210 +/- 15 (+/- SEM) and 200 +/- 17 mg/min during saline and EPI treatment, respectively (P = NS). Therefore, EPI has no ability to modulate NIMGU. To measure the effect of EPI on Rd, hyperglycemic (200 mg/dL) hyperinsulinemic clamp (30 mU/M2 X min) studies were performed during the infusion of saline and EPI. EPI decreased Rd by 46 +/- 6% (751 +/- 85 to 405 +/- 43 mg/min; P less than 0.01). When the effect of EPI on IMGU (Rd - NIMGU) was considered separately, the inhibitory effect of EPI was more potent, as indicated by a 61 +/- 12% decrease in IMGU. In conclusion, 1) EPI inhibits IMGU, but has no effect on NIMGU; 2) when NIMGU is taken into account, EPI has a more potent ability to inhibit IMGU than previously found; and 3) the systems responsible for NIMGU and IMGU are independently regulated. 相似文献
9.
Contrasting effects of L-arginine on insulin-mediated blood flow and glucose disposal in the elderly
Insulin increases skeletal muscle blood flow in healthy young subjects by a nitric oxide (NO)-dependent mechanism. Impairment of this mechanism may contribute to the insulin resistance of normal aging. We tested the hypothesis that L-arginine, the endogenous precursor for NO synthesis, would augment insulin-mediated vasodilation and in so doing increase insulin-mediated glucose uptake (IMGU) in healthy elderly subjects. Experiments were conducted on healthy young (n = 9; age, 24 +/- 1 years; body mass index, 24 +/- 1 kg/m2) and old (n = 9; age, 77 +/- 2 years; BMI, 25 +/- 1 kg/m2) subjects. Each underwent two euglycemic clamp studies. On both occasions, insulin was infused from 0 to 120 minutes (young, 40 mU/m2/min; old, 34 mU/m2/min). On 1 day, insulin was continued and L-arginine (7.5 mg/kg/min) was coinfused from 120 to 240 minutes. On the second study day, the insulin infusion from 120 minutes onward was adjusted in each subject to match corresponding plasma concentrations during the L-arginine infusion. Calf blood flow was measured bilaterally using venous occlusion plethysmography. Mean arterial blood pressure decreased in response to L-arginine in both young (77 +/- 1 v 73 +/- 1 mm Hg; P < .05) and old (103 +/- 2 v 94 +/- 2 mm Hg; P < .01). Calf vascular conductance increased in young (from 0.094 +/- 0.009 to 0.113 +/- 0.012 mL/100 mL/min/mm Hg; P < .01) and old (from 0.035 +/- 0.003 to 0.050 +/- 0.003 mL/100 mL/min/mm Hg; P < .01), consistent with the concept that the addition of substrate can augment skeletal muscle endothelial NO production in both age groups. Calf blood flow increased in both young (control, 7.04 +/- 0.73; L-arginine, 8.02 +/- 0.78 mL/100 mL/min; P < .05) and old (control, 3.60 +/- 0.27: L-arginine, 4.65 +/- 0.23 mL/100 mL/min; P < .0001) subjects, yet L-arginine had no impact on glucose disposal in either age group. In conclusion, L-arginine caused skeletal muscle vasodilation in the elderly, indicating that this endothelially mediated response is not attenuated with age. However, this increase in blood flow had no impact on insulin-mediated glucose uptake. 相似文献
10.
J Arnfred O Schmitz O Hother-Nielsen C Orskov H Beck-Nielsen K Hermansen J S Christiansen K G Alberti H Orskov 《Diabetic medicine》1988,5(8):755-760
The effect of hyperglycaemia per se on glucose utilization and glucose production was evaluated in 12 patients with insulin-dependent diabetes and in 9 non-diabetic control subjects. In diabetic patients normoglycaemia was maintained during the night preceding the study by a variable intravenous insulin infusion. During the study endogenous insulin secretion was suppressed by somatostatin (300 micrograms h-1) and replaced by infusion of insulin (0.2 mU kg-1 min-1). Glucose utilization and hepatic glucose production rates were quantified at two plasma glucose concentrations (6.7 and 16.7 mmol l-1) using the two-step sequential hyperglycaemic clamp technique in combination with 3-3H-glucose tracer infusion. Duration of each step was 120 min. In diabetic patients glucose utilization, at a glucose concentration of 6.7 mmol l-1, was not different from normal (mean +/- SE: 2.9 +/- 0.2 vs 3.6 +/- 0.3 mg kg-1 min-1, 0.05 less than p less than 0.10), but the response to marked hyperglycaemia was significantly reduced (5.4 +/- 0.5 vs 9.4 +/- 1.0 mg kg-1 min-1, p less than 0.01). Hepatic glucose production was also normal at 6.7 mmol l-1 (1.4 +/- 0.1 vs 1.4 +/- 0.1 mg kg-1 min-1, NS), but whereas in control subjects glucose production was suppressed during hyperglycaemia of 16.7 mmol l-1 (0.3 +/- 0.4 mg kg-1 min-1, p less than 0.01), a slight increase was observed in diabetic patients (2.0 +/- 0.2 mg kg-1 min-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
11.
The purpose of the present study was to determine if the improvement in insulin sensitivity after resistance training (RT) is associated with a decline in plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptor 1 (sTNF R1), and soluble TNF receptor 2 (sTNF R2). Eleven older hypertensives (5 men/6 women, 67 +/- 2 years) participated in a 4-month RT program. Following RT there was a significant increase in upper body (P =.029) and lower body strength (P =.001), assessed by the bench press 1-repetition maximum (1RM) and leg press 1RM, respectively. The RT program produced a significant increase in lean body mass (LBM) (P =.029), a trend for a decline in percent body fat (P =.083), and no change in total body mass (P =.958). Insulin-mediated glucose disposal, assessed by the hyperinsulinemic euglycemic clamp procedure, significantly increased following RT (P =.026). Despite the increase in insulin action, plasma levels of TNF-alpha, sTNF R1, and sTNF R2 were not significantly altered by RT (TNF-alpha: P =.118, sTNF R1: P =.184, sTNF R2: P =.168). In conclusion, a 4-month RT program significantly increased insulin-mediated glucose disposal and LBM without a significant reduction in plasma levels of TNF-alpha, sTNF R1, and sTNF R2 in older hypertensive subjects. 相似文献
12.
This study was initiated to test the hypothesis that plasma homocysteine concentrations are increased in insulin resistant individuals. For this purpose, the relationship between insulin resistance, as assessed by the steady-state plasma glucose (SSPG) concentration during the insulin suppression test, and fasting plasma homocysteine concentration was defined in 55 healthy volunteers. The results indicated that homocysteine concentrations did not vary as a function of SSPG concentrations (r = 0.02, P = 0.88). Furthermore, mean (+/- S.E.M.) plasma homocysteine concentrations were similar (8.2+/-0.4 vs. 8.7+/-0.7 micromol/l) in individuals classified as being either insulin sensitive (SSPG <100 mg/dl) or insulin resistant (SSPG >180 mg/dl). On the other hand, SSPG concentration was significantly correlated with fasting plasma insulin (r = 0.58, P<0.001), triglycerides (r = 0.34, P<0.05), and HDL-cholesterol (r = -0.36, P = 0.04) concentrations. These data strongly suggest that the increased risk of atherosclerosis associated with increased plasma homocysteine concentrations is unrelated to insulin resistance and/or the metabolic abnormalities associated with it. 相似文献
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I Nosari G Lepore M L Maglio F Cortinovis G Pagani 《Journal of endocrinological investigation》1992,15(2):143-146
We investigated how different plasma glucose concentrations could significantly modify the C-peptide response to glucagon. Twenty poorly-controlled (HbA1c 10.2 +/- 1.5%) non insulin-dependent (NIDDM) subjects (body mass index 27 +/- 1.8), 2 treated with diet alone and 18 with oral hypoglycemic agents were studied. The first day glucagon (1 mg iv) was injected, patients being fasting and untreated. Mean plasma glucose levels were 11.4 +/- 1.2 mM. On a second non consecutive day, after an overnight fast, the same patients were connected to a closed-loop insulin infusion system (Betalike, Genoa), their blood glucose concentrations were stabilized within a normoglycemic range (5-5.5 mM) for 2 h and insulin infusion was stopped. The glucagon test was repeated 30 min later. Blood samples were taken 0, 6, 10, 20 min after glucagon injection. In the second test, basal, and 6, 10 and 20 min post-glucagon glucose levels were significantly lower (p less than 0.001); similarly C-peptide concentrations were significantly reduced both in basal conditions (0.55 +/- 0.04 vs 0.37 +/- 0.04 nM; p less than 0.001) and 6 (0.92 +/- 0.06 vs 0.6 +/- 0.06; p less than 0.001), 10 (0.79 +/- 0.06 vs 0.56 +/- 0.06; p less than 0.001) and 20 min (0.64 +/- 0.05 vs 0.44 +/- 0.04; p less than 0.001) after stimulation. The C-peptide secretion area showed the same trend (49.5 +/- 4.8 vs 32.1 +/- 5.8; p less than 0.001). In conclusion, our data confirms that blood glucose levels modulate the pancreatic insulin secretion; glycemic normalization significantly reduced both basal and post-glucagon C-peptide release. 相似文献
16.
Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in thyrotoxicosis: a minimal model analysis 总被引:1,自引:0,他引:1
In order to evaluate simultaneously in thyrotoxic subjects the relative contributions of insulin secretion, insulin-sensitivity (SI) and glucose-mediated (SG) glucose disposal to overall glucose tolerance, seven non-obese patients with thyrotoxicosis were studied by the minimal model analysis of the frequently sampled intravenous glucose tolerance test, before and greater than 1 month after being rendered euthyroid, and compared with eight healthy control subjects. Basal glucose, C-peptide and glucagon levels were similar in all groups but, in the toxic and euthyroid states, basal insulin levels were significantly elevated compared to the control group (11.2 +/- 2.0 and 7.9 +/- 1.1 vs 5.1 +/- 0.6 microU/ml, mean +/- SE, P less than 0.02). FFA levels were raised in the thyrotoxic subjects prior to treatment (0.95 +/- 0.11 vs 0.68 +/- 0.08 and 0.54 +/- 0.08 mmol/l, P less than 0.02). Glucose tolerance (Kg) was reduced in the thyrotoxic subjects compared to the euthyroid state (1.16 +/- 0.12 vs 1.44 +/- 0.13 per min, P less than 0.025) and control group (1.44 +/- 1.0 per min, 0.05 less than P less than 0.1). First phase (phi 1) and second phase (phi 2) insulin release were both significantly elevated in the thyrotoxic and euthyroid states compared to the control group (phi 1 7.10 +/- 1.88 and 5.29 +/- 1.03 vs 1.72 +/- 0.17 microU/mg/min X 10(-2), P less than 0.01; phi 2 18.64 +/- 3.14 and 16.74 +/- 4.48 vs 9.23 +/- 0.74 microU/mg/min X 10(-2) respectively, P less than 0.02). SG was similar in all groups but SI was significantly reduced in the thyrotoxic subjects compared to the control group (2.24 +/- 0.62 vs 5.92 +/- 1.50/min/microU/ml X 10(4), P less than 0.02) and rose post-treatment in the euthyroid subjects (4.23 +/- 1.75/min/microU/ml X 10(4)). In the thyrotoxic subjects before and after treatment, log SI correlated negatively with basal FFA levels (r = -0.57, P less than 0.05) and with phi 2 (r = -0.58, P less than 0.05). The fractional clearance rate of insulin was unaltered by the thyrotoxic state. It is concluded that in thyrotoxicosis the impairment of Kg is due to reduced insulin sensitivity in the presence of enhanced insulin secretion, but glucose-mediated glucose disposal is unaltered by the toxic state. 相似文献
17.
To evaluate the effect of beta 1-blockade (metoprolol) on the plasma glucose thresholds initiating counterregulatory hormone responses and symptoms of hypoglycemia, we used a modified glucose clamp technique to produce a standardized gradual glucose decline from 5.0 to 2.0 mmol/l in nine patients with insulin-dependent diabetes mellitus (IDDM) (HbAlc range 6.7-10.3%, duration of diabetes 5-18 years, autonomous neuropathy present in three of the patients). The responses were studied once with metoprolol and once with placebo, in random order. With the beta 1-selective blockade, epinephrine release was triggered at a significantly higher (p less than 0.02) plasma glucose level (3.5 mmol/l) than it was with placebo (3.0 mmol/l). Metoprolol did not change thresholds for growth hormone (3.7/3.5 mmol/l), cortisol (2.9/2.9 mmol/l), glucagon (2.8/2.8 mmol/l) or for pancreatic polypeptide (2.8/2.7 mmol/l). The peak responses of epinephrine and growth hormone were significantly higher (p less than 0.01) with the beta 1-blockade. Metoprolol did not change the thresholds for neuroglycopenic and autonomic symptoms. Six out of the seven patients who answered yes to having hypoglycemia did so at a higher blood glucose with metoprolol than without. In our study, the beta 1-selective blockade altered the responses of counterregulatory hormones, but it did not change the thresholds for hypoglycemic symptoms. 相似文献
18.
The effect of starvation on insulin-induced glucose disposal and thermogenesis in humans 总被引:7,自引:0,他引:7
The effect of 48-hour starvation on glucose metabolism was studied in six non-diabetic, normal weight men using a hyperinsulinemic (100 mU/min/m2) glucose clamp (3.5 mmol/L). The rate of glucose oxidation was calculated from measurements of respiratory gas exchange, after allowing for the oxidation of ketones and of protein. During the glucose clamp, the whole body glucose disposal rate decreased from 39.8 (SEM 4.6) mumol/kg/min in the fed state to 24.1 (2.1) mumol/kg/min in the starved state (P less than .01), consistent with insulin "resistance." The glucose oxidation rate decreased from 21.8 (1.3) to 3.9 (1.4) mumol/kg/min with starvation (P less than .001), but the nonoxidative glucose disposal rate was unchanged (18.0 [3.9] mumol/kg/min normally fed, and 20.2 [1.2] mumol/kg/min starved). With starvation, the rate of glucose uptake in the forearm during the glucose clamp was reduced from 59.4 to 15.4 mumol/min/L forearm (SE 5.6, P less than .01, ANOVA). There was a significant net increase in thermogenesis during the glucose clamp in the normally fed state (0.27 [0.08] kJ/min, P less than .01, ANOVA), but not following starvation (0.11 [0.09] kJ/min, NS, ANOVA). Therefore, starvation caused decreases in oxidative glucose disposal and in forearm glucose uptake; despite the whole body nonoxidative disposal rate of glucose being unchanged, the associated net thermogenic response was diminished. 相似文献
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Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in Cushing''s disease: a minimal model analysis 总被引:1,自引:0,他引:1
Renee Page Mltra Boolell Anna Kalfas Steven Sawyer R. Pestell Glenn Ward Frank Alford 《Clinical endocrinology》1991,35(6):509-517
OBJECTIVE: We wished to assess the contributions of insulin secretion, insulin sensitivity and glucose-mediated glucose disposal to glucose tolerance in subjects exposed to chronic glucocorticoid excess. DESIGN: Patients with Cushing's disease were subjected to a frequently sampled intravenous glucose tolerance test before and at least 3 months after curative surgery and compared to a control group. PATIENTS: Seven patients with clinical and biochemically proven pituitary dependent Cushing's disease and 10 healthy control subjects were studied. MEASUREMENTS: Paired glucose and insulin plasma profiles were analysed by the Minimal Model method of Bergman, which provided simultaneous estimates of the glucose decay rate, insulin secretion, insulin sensitivity and glucose-mediated and non-insulin-mediated glucose disposal. Data were evaluated by non-parametric statistical analysis and reported as median and interquartile ranges. RESULTS: Basal glucose, insulin, C-peptide and glucagon levels were significantly raised preoperatively and fell towards normal post-operatively. Glucose tolerance assessed as glucose decay rate was reduced significantly preoperatively (pre: 1.3 (0.8-2.0) vs post: 1.6 (1.5-2.6) per min x 10(2), P less than 0.05). First phase insulin release was similar in the Cushing's disease and control subjects. In contrast, second phase insulin release was significantly greater preoperatively and remained high post-operatively compared to control subjects (pre: 18.8 (16.7-23.6) vs post: 16.7 (8.5-18.8) vs control 11.1 (4.5-15.4) mU/g/min2 x 10(-2), P less than 0.002). Median insulin sensitivity was reduced by 60% preoperatively in the Cushing's disease subjects compared to the post-operative Cushing's disease and control subjects (pre: 2.1 (1.3-4.2) vs post: 5.0 (3.2-7.3) vs control 5.1 (2.2-7.2) per min/mU/l x 10(4)). Median glucose-mediated glucose disposal was reduced by 40% in the pre and post-operative Cushing's disease subjects compared to the control group (pre: 1.1 (0.6-2.1) vs post: 1.1 (0.6-2.1) vs control 1.9 (1.4-2.6) per min x 10(2)), but this was not statistically significant. However, non-insulin-mediated glucose disposal was significantly reduced in the preoperative Cushing's disease subjects (pre: 0.55 (0.08-1.59) vs control 1.43 (0.94-2.27) per min x 10(2), P less than 0.05). In the Cushing's disease subjects, glucose tolerance correlated with both insulin sensitivity (rs = 0.84, P less than 0.01) and non-insulin-mediated glucose disposal (rs = 0.56, P less than 0.05). The fractional clearance rate of insulin was unaltered by Cushing's disease. CONCLUSIONS: Cushing's disease subjects are characterized by impaired glucose tolerance due to both reduced insulin sensitivity and non-insulin-mediated glucose disposal, in the presence of enhanced insulin secretion. 相似文献