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Biomedical subjects

A D Baron

Publications and source records attributed to A D Baron.

At least 55 records · Page 3Linked to original sources
PubMed1996

Insulin and the vasculature--old actors, new roles.

I have presented data to support an interaction of insulin with the vascular endothelium to cause the release of NO and vasodilation. In effect, insulin-mediated vasodilation can be viewed as a novel test of endothelial function. The physiologic significance of insulin-mediated, endothelium-dependent vasodilation is not fully understood, but some insight has been gained. Insulin-mediated vasodilation in skeletal muscle appears to be an important mechanism to amplify insulin's overall action to stimulate skeletal muscle glucose uptake in insulin-sensitive man. Insulin-resistant states of obesity, hypertension, and NIDDM exhibit blunted insulin-mediated vasodilation and impaired endothelium-dependent vasodilation. Together, the data suggest that endothelial dysfunction is an integral aspect of the syndrome of insulin resistance, independent of hyperglycemia, and as such may contribute to worsen insulin resistance, increase vascular reactivity, 32 and predispose to macrovascular disease. Thus, the insulin/EDNO interaction provides a potential mechanism (but certainly not the only one) linking insulin resistance, hypertension, thrombosis, and atherosclerosis-key features of the insulin resistance syndrome (Figure 7). Future research into the signal transduction steps leading to insulin-mediated, endothelium-derived NO production and its dysregulation in insulin-resistant states will be extremely useful to elucidate the mechanisms underlying the increased macrovascular risk in insulin-resistant man.

Blood Vessels↗
PubMed1995

Magnesium deficiency enhances basal glucose disposal in the rat.

To investigate the contribution of hepatic and peripheral tissues to the enhanced glucose disposal rate (Kg) observed in magnesium (Mg)-deficient rats, euglycemic-hyperinsulinemic clamps were performed with continuous infusion of [3-3H]glucose and three insulin infusion rates, 1, 8, and 16 microU.kg-1.min-1. Moderately Mg-deficient (Mg-, 4.2 microM Mg/g diet) and Mg-adequate (Mg+, 16.7 microM Mg/g diet) Sprague-Dawley rats were studied after 3 wk of dietary treatment. Growth, fasting glucose, and insulin concentrations were not affected by dietary treatment. Basal hepatic glucose output (HGO) and glucose disposal (Rd) were increased by 24% in Mg- rats (P < 0.001). After 1 microU insulin.kg-1.min-1 infusion, Rd and the glucose infusion rate that maintained euglycemia were significantly increased in Mg- rats by 24 and 46%, respectively. However, when the increase in Rd above baseline was examined, no significant differences were observed. Therefore, the increased basal glucose disposal observed in Mg- rats may be mediated by noninsulin-dependent mechanisms. Insulin suppression of HGO during 1 microU insulin.kg-1.min-1 infusion was greater in Mg- rats (43%) compared with Mg+ rats (27%, P < 0.05). In conclusion, the increased Kg observed in Mg- rats is likely to be caused by an increase in noninsulin-mediated glucose uptake and an enhancement of hepatic insulin sensitivity.

Animals↗
PubMed1995

Insulin resistance after hypertension induced by the nitric oxide synthesis inhibitor L-NMMA in rats.

To explore the relationship between insulin resistance and hypertension, we examined whether acute induction of hypertension can engender insulin resistance. For this purpose we measured rates of insulin-mediated glucose uptake in awake unstressed rats with the euglycemic hyperinsulinemic (12 microns.kg-1.min-1) clamp technique during infusions of saline alone or after induction of hypertension by bolus administration of NG-monomethyl-L-arginine (L-NMMA, 30 and 15 mg/kg), a competitive inhibitor of nitric oxide synthase. Arterial pressure was approximately 20% greater with L-NMMA bolus than with saline alone. Isotopically determined steady-state rates of glucose uptake were 36 +/- 1 mg.kg-1.min-1 during saline alone and 26 +/- 2 and 19 +/- 1 mg.kg-1.min-1 with low- and high-dose L-NMMA (P < 0.001 vs. saline), respectively. To rule out that insulin resistance induced by L-NMMA was adrenergically mediated, clamp studies were repeated with alpha- and beta-blockade. Rates of glucose uptake remained approximately 20% below those observed with saline alone (P < 0.001). A significant inverse correlation was observed between the height of the blood pressure and the rate of glucose uptake (r = 0.32, P = 0.04). In conclusion, acute induction of hypertension with L-NMMA can cause marked insulin resistance. We postulate that reduced skeletal muscle perfusion and/or sympathetic nervous system activation may contribute to insulin resistance induced by L-NMMA.

Animals↗
PubMed1995

Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans.

Whether insulin-mediated vasodilation is important in determining insulin's overall action to stimulate glucose uptake is unknown. To this end, we measured leg glucose uptake during euglycemic hyperinsulinemic clamps performed at two insulin doses (40 mU/m2 per min, n = 6 and 120 mU/m2 per min, n = 15) alone and during a superimposed intrafemoral artery infusion of GN-monomethyl-L-arginine (L-NMMA) designed to blunt insulin-mediated vasodilation. During the higher dose study, hyperinsulinemia resulted in about a twofold rise in basal leg blood flow from 0.24 +/- 0.02 to 0.45 +/- 0.05 liter/min, P < 0.0001. L-NMMA infusion resulted in a net 21% reduction in leg glucose uptake from 114 +/- 18 mg/min to 85 +/- 13 mg/min, P < 0.001. We also found a significant relationship between the rate of insulin-stimulated whole body glucose uptake and the magnitude of flow dependent glucose uptake (r = 0.57, P = 0.02). Data obtained during the lower dose insulin infusion resulted in similar findings. In conclusion, in healthy lean subjects, insulin-stimulated muscle blood flow contributes to both insulin responsiveness and insulin sensitivity. The most insulin-sensitive subjects appear to be the most reliant on muscle perfusion for insulin action. Insulin-mediated vasodilation is an important physiological determinant of insulin action.

Adult↗
PubMed1995

Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity.

Glucosamine (Glmn), a product of glucose metabolism via the hexosamine pathway, causes insulin resistance in isolated adipocytes by impairing insulin-induced GLUT 4 glucose transporter translocation to the plasma membrane. We hypothesized that Glmn causes insulin resistance in vivo by a similar mechanism in skeletal muscle. We performed euglycemic hyperinsulinemic clamps (12 mU/kg/min + 3H-3-glucose) in awake male Sprague-Dawley rats with and without Glmn infusion at rates ranging from 0.1 to 6.5 mg/kg/min. After 4h of euglycemic clamping, hindquarter muscles were quick-frozen and homogenized, and membranes were subfractionated by differential centrifugation and separated on a discontinuous sucrose gradient (25, 30, and 35% sucrose). Membrane proteins were solubilized and immunoblotted for GLUT 4. With Glmn, glucose uptake (GU) was maximally reduced by 33 +/- 1%, P < 0.001. The apparent Glmn dose to reduce maximal GU by 50% was 0.1 mg/kg/min or 1/70th the rate of GU on a molar basis. Control galactosamine and mannosamine infusions had no effect on GU. Relative to baseline, insulin caused a 2.6-fold increase in GLUT 4 in the 25% membrane fraction (f), P < 0.01, and a 40% reduction in the 35%f, P < 0.05, but had no effect on GLUT 4 in the 30% f, P= NS. Addition of Glmn to insulin caused a 41% reduction of GLUT 4 in the 25%f, P < 0.05, a 29% fall in the 30%f, and prevented the reduction of GLUT 4 in the 35% f. The 30%f membranes were subjected to a second separation with a 27 and 30% sucrose gradient. Insulin mobilized GLUT 4 away from the 30%f, P < 0.05, but not the 27% f. In contrast, Glmn reduced GLUT 4 in the 27%f, P < 0.05, but not the 30%f. Thus Glmn appears to alter translocation of an insulin-insensitive GLUT 4 pool. Coinfusion of Glmn did not alter enrichment of the sarcolemmal markers 5'-nucleotidase, Na+/K+ATPase, and phospholemman in either 25, 30, or 35% f. Thus Glmn completely blocked movement of Glut 4 induced by insulin. Glmn is a potent inducer of insulin resistance in vivo by causing (at least in part) a defect intrinsic to GLUT 4 translocation and/or trafficking. These data support a potential role for Glmn to cause glucose-induced insulin resistance (glucose toxicity).

Animals↗
PubMed1995

Skeletal muscle proteolysis is reduced in noninsulin-dependent diabetes mellitus and is unaltered by euglycemic hyperinsulinemia or intensive insulin therapy.

To assess how noninsulin-dependent diabetes mellitus (NIDDM) and diabetes control may alter whole body and skeletal muscle proteolysis, we measured the rate of appearance (Ra) of phenylalanine (reflecting proteolysis) in the whole body and across the leg (reflecting skeletal muscle), using a constant tracer infusion of [2H5]phenylalanine in the basal state and during high-dose euglycemic hyperinsulinemia in 6 NIDDM and 10 control subjects. Studies were performed in NIDDM subjects 2 weeks after complete withdrawal of antidiabetic treatment and again after intensive insulin therapy. After intensive treatment, significant reductions were measured in hemoglobin A1C, fasting glucose concentrations, and basal hepatic glucose output. In contrast, there was no change after therapy in basal whole body or leg phenylalanine Ra. Compared with that of controls, whole body phenylalanine Ra was significantly higher and leg phenylalanine Ra significantly lower in NIDDM subjects. During euglycemic hyperinsulinemia, whole body phenylalanine Ra was significantly suppressed (approximately 15%) below basal values before and after therapy in NIDDM subjects and similarly suppressed in control subjects. However, in NIDDM subjects, euglycemic hyperinsulinemia did not reduce leg phenylalanine Ra below basal values either before or after therapy, whereas hyperinsulinemia resulted in a 42% suppression of leg phenylalanine Ra in controls. We conclude that 1) the clear improvement in glucose metabolism produced by intensive insulin therapy in NIDDM is not accompanied by changes in whole body or skeletal muscle proteolysis; 2) skeletal muscle proteolysis is reduced even though whole body proteolysis is increased in NIDDM subjects compared with controls; and 3) although a high-dose systemic infusion of insulin significantly reduces whole body proteolysis in both NIDDM and control subjects, skeletal muscle proteolysis is suppressed only in controls. We speculate that in NIDDM, high basal insulin concentrations (approximately 200 pmol/L, unaltered by therapy) maximally suppress skeletal muscle proteolysis, and therefore higher insulin concentrations produce no additional suppression in skeletal muscle.

Adult↗
PubMed1994

Pathogenesis and measurement of insulin resistance in hypertension.

Because of its association with a constellation of cardiovascular risk factors, insulin resistance has recently emerged as a major clinical disorder. There is therefore an increasing need to accurately assess insulin sensitivity in clinical and epidemiologic studies. The merits of various techniques for measuring insulin action are briefly reviewed. Essential hypertension and insulin resistance appear to be tightly linked; however, the mechanism or mechanisms accounting for this association are not known. Central or intra-abdominal obesity is a particularly strong risk factor for the development of hypertension. The weight of the evidence suggests that hyperinsulinemia per se is not a potent instrumental factor in the development of hypertension. Mechanisms suggesting that insulin resistance independent of hyperinsulinemia may predispose to increased vascular tone are discussed. Conversely, the possibility that essential hypertension could engender insulin resistance is proposed. The link between insulin resistance and hypertension is likely to be complex and multifactorial.

Glucose Tolerance Test↗
PubMed1994

Skeletal muscle blood flow independently modulates insulin-mediated glucose uptake.

Insulin-mediated glucose uptake (IMGU) occurs principally in skeletal muscle. To directly examine whether skeletal muscle perfusion (F) can directly and independently modulate IMGU, we combined the hyperinsulinemic euglycemic clamp and leg balance techniques [leg glucose uptake (LGU) = arteriovenous glucose difference (delta AVG) x F]. Young (< 40 yr) healthy lean subjects were studied during euglycemic hyperinsulinemia of approximately 23 microU/ml (group I, n = 8) and approximately 950 microU/ml (group II, n = 6). Femoral delta AVG and leg F were measured, and LGU was calculated at baseline after approximately 200 min of steady-state hyperinsulinemia alone and during a superimposed intrafemoral artery infusion of methacholine hydrochloride designed to increase leg F two- to threefold. In groups I and II, insulin raised the delta AVG approximately 4- and 14-fold, respectively (P < 0.0001). Leg F was unchanged during the low-dose insulin infusion (group I) but increased 112 +/- 35% in group II (P < 0.001). During methacholine infusion the delta AVG narrowed 35.9 +/- 6.8% (P < 0.01) and 20.5 +/- 4.8% (P < 0.05) in groups I and II, respectively. Leg F rose 224 +/- 30% (P < 0.01) and 79 +/- 13% (P < 0.05) above the flow rate achieved with insulin alone. Thus, during methacholine flow modulation, LGU increased 116 +/- 36% (P < 0.01) and 47 +/- 11% (P < 0.05) in groups I and II, respectively. In conclusion, skeletal muscle perfusion during hyperinsulinemia can act as an independent determinant of IMGU.

Adult↗
PubMed1994

Hemodynamic actions of insulin.

There is accumulating evidence that insulin has a physiological role to vasodilate skeletal muscle vasculature in humans. This effect occurs in a dose-dependent fashion within a half-maximal response of approximately 40 microU/ml. This vasodilating action is impaired in states of insulin resistance such as obesity, non-insulin-dependent diabetes, and elevated blood pressure. The precise physiological role of insulin-mediated vasodilation is not known. Data indicate that the degree of skeletal muscle perfusion can be an important determinant of insulin-mediated glucose uptake. Therefore, it is possible that insulin-mediated vasodilation is an integral aspect of insulin's overall action to stimulate glucose uptake; thus defective vasodilation could potentially contribute to insulin resistance. In addition, insulin-mediated vasodilation may play a role in the regulation of vascular tone. Data are provided to indicate that the pressor response to systemic norepinephrine infusions is increased in obese insulin-resistant subjects. Moreover, the normal effect of insulin to shift the norepinephrine pressor dose-response curve to the right is impaired in these patients. Therefore, impaired insulin-mediated vasodilation could further contribute to the increased prevalence of hypertension observed in states of insulin resistance. Finally, data are presented to indicate that, via a yet unknown interaction with the endothelium, insulin is able to increase nitric oxide synthesis and release and through this mechanism vasodilate. It is interesting to speculate that states of insulin resistance might also be associated with a defect in insulin's action to modulate the nitric oxide system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. Studies in lean and obese men.

To explore the interactions between insulin action and norepinephrine (NE) on blood pressure and muscle vascular resistance, we studied seven lean (66 +/- 1 kg) sensitive and seven age-matched obese (96 +/- 3 kg) insulin-resistant men after an overnight fast. Both groups were normotensive; however, the obese exhibited higher basal blood pressure, 90.8 +/- 2.2 vs. 83.4 +/- 1.6 mmHg, P < 0.04. Each subject was studied on two separate days during either saline (S) infusion or a euglycemic hyperinsulinemic clamp (I) achieving insulin concentrations of approximately 70 microU/ml. After 180 min of either S or I, NE was infused systemically at rates of approximately 50, 75, and 100 pg/kg per min. Glucose uptake was measured in whole body ([3-3H]glucose) and in leg by the balance technique. The results indicate: (a) the NE/pressor dose-response curve was decreased (shifted to the right) during I in lean but not in obese subjects, (b) I enhanced NE metabolic clearance by 20% in lean but not in obese, (c) NE decreases leg vascular resistance more in lean than in obese, and (d) NE causes a approximately 20% increase in insulin-mediated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE pressor sensitivity and decreased NE metabolic clearance. Both of these mechanisms can potentially contribute to the higher incidence of hypertension in obese man. Insulin resistance is likely to be a predisposing but not sufficient factor in the pathogenesis of hypertension. Because the obese group exhibited higher basal blood pressure, it is possible that our results reflect this difference. Further studies will be required to clarify this issue.

Blood Glucose↗
PubMed1994

Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.

The purpose of this study was to examine whether insulin's effect to vasodilate skeletal muscle vasculature is mediated by endothelium-derived nitric oxide (EDNO). N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, was administered directly into the femoral artery of normal subjects at a dose of 16 mg/min and leg blood flow (LBF) was measured during an infusion of saline (NS) or during a euglycemic hyperinsulinemic clamp (HIC) designed to approximately double LBF. In response to the intrafemoral artery infusion of L-NMMA, LBF decreased from 0.296 +/- 0.032 to 0.235 +/- 0.022 liters/min during NS and from 0.479 +/- 0.118 to 0.266 +/- 0.052 liters/min during HIC, P < 0.03. The proportion of NO-dependent LBF during NS and HIC was approximately 20% and approximately 40%, respectively, P < 0.003 (NS vs. HIC). To elucidate whether insulin increases EDNO synthesis/release or EDNO action, vasodilative responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP) were studied in normal subjects during either NS or HIC. LBF increments in response to intrafemoral artery infusions of MCh but not SNP were augmented during HIC versus NS, P < 0.03. In summary, insulin-mediated vasodilation is EDNO dependent. Insulin vasodilation of skeletal muscle vasculature most likely occurs via increasing EDNO synthesis/release. Thus, insulin appears to be a novel modulator of the EDNO system.

Adult↗
PubMed1993

Cardiovascular actions of insulin in humans. Implications for insulin sensitivity and vascular tone.

Insulin has a plethora of actions, most of which are initiated after interaction with its specific cell surface receptor on classical target tissues. Prominent among these actions is its ability to increase cellular permeability to glucose in muscle and fat. Heretofore, the cardiovascular actions of insulin in humans have received little attention. The effects of insulin on the cardiovascular system and, in particular, on skeletal muscle vasculature are physiological, specific, co-ordinated and appear to play an integral part in its overall action to promote the disposal of glucose and probably other substrates. The vascular actions of insulin should be added to the long list of actions initiated by this hormone, and are important to consider in the study of in vivo metabolism in health and disease.

Cardiovascular Diseases↗
PubMed1993

Insulin differentially regulates systemic and skeletal muscle vascular resistance.

To explore the relationships among insulin action, vascular resistance, and insulin sensitivity, we studied three groups of lean (Ln) and one group of obese (Ob) men. Glucose uptake was measured in whole body (WBGU) and in leg muscle (LGU) under basal and hyperinsulinemic euglycemic conditions. Mean arterial pressure (MAP), cardiac output (CO), leg blood flow (LBF), and systemic (SVR) and leg (LVR) vascular resistance were also ascertained. Ln groups were studied during insulin infusion rates of 20, 40, and 600 mU.m-2.min-1 and the Ob group at 40 mU.m-2.min-1. In Ob vs. Ln groups, WBGU and LGU were reduced by 51 (P < 0.01) and 42% (P < 0.05), respectively. In response to insulin, LBF increased > 60% (P < 0.01) in Ln groups but only approximately 20% in the Ob group, P = not significant (NS). CO was unchanged in Ob compared with a 15% increase (P < 0.05) in Ln groups, LBF was highly correlated with CO, r 0.70, P < 0.001. During hyperinsulinemia, MAP and LVR decreased in Ln (P < 0.001) but not in the Ob group (P = NS). In Ln groups, SVR decreased by 26 vs. 9% in the Ob group, P < 0.01. In summary, 1) insulin decreases LVR more than SVR and via this mechanism redistributes CO to insulin-sensitive tissues, 2) this insulin effect is blunted in Ob humans, and 3) insulin decreases MAP and vascular resistance more effectively in insulin-sensitive than in insulin-resistant subjects. In conclusion, insulin resistance to carbohydrate metabolism is associated with resistance to insulin's effect to decrease skeletal muscle vascular resistance and as such could act as a risk factor for the development of hypertension.

Animals↗
PubMed1993

Skeletal muscle blood flow. A possible link between insulin resistance and blood pressure.

Insulin resistance has recently been found to be a common feature of essential hypertension. We have tested the hypothesis that reduced skeletal muscle blood flow in response to insulin may at least partially account for the wide range of insulin sensitivity observed in normotensive subjects. To this end, we studied 19 lean (body mass index < or = 27) subjects exhibiting basal mean arterial pressures ranging from 58 to 110 mm Hg. All subjects were normotensive with the exception of one. Each subject was studied at baseline and during a hyperinsulinemic (600 milliunits/m2 per minute) euglycemic clamp to quantitate insulin sensitivity. Mean arterial pressure was monitored invasively, and both leg (muscle) blood flow and cardiac output were measured by indicator dilution techniques, allowing the determination of both systemic and leg (or muscle) vascular resistance. In response to hyperinsulinemia, both cardiac output and leg blood flow increased approximately 37% and 80% (p < 0.01), respectively. Rates of insulin-mediated glucose uptake were inversely correlated with the baseline mean arterial pressure (r = -0.62, p < 0.01). The individual increment in leg blood flow above baseline in response to insulin was inversely proportional to the height of the baseline mean arterial pressure (r = -0.59, p < 0.01). Mean arterial pressure and insulin-mediated glucose uptake were not correlated with either age or body fat content.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Pseudomonas aeruginosa bronchopulmonary infection in late human immunodeficiency virus disease.

Pseudomonas aeruginosa infection is unusual in individuals with human immunodeficiency virus infection, and it most often occurs in the setting of other risk factors, such as neutropenia or cytotoxic drug use. We noted an increasing number of pulmonary isolates of this organism in our clinic population and sought to describe the clinical correlates of this finding. Our study consisted of a retrospective review of the microbiology, radiology, and clinical records of 1,852 HIV-seropositive adults seen at a university-based outpatient AIDS clinic. We identified 16 individuals with Pseudomonas bronchopulmonary infection. All subjects had advanced HIV disease with prior AIDS diagnoses, and mean CD4 counts of 25/mm3 (0.025 x 10(9)/L). Pseudomonas was the sole pulmonary pathogen in 14 of 16 patients and was associated with new chest X-ray abnormalities in 14 cases. Four individuals had acute pseudomonal pneumonia with sepsis; this presentation was associated with hospitalization and other known risk factors for Pseudomonas infection. In contrast, 12 patients had more indolent, community-acquired infection, which had a low mortality rate and occurred in the absence of other risk factors. Survivors of the initial bout of Pseudomonas infection had an 86% relapse rate despite a median survival of only 4.5 months. This pattern of pseudomonal disease is reminiscent of cystic fibrosis and suggests a role for maintenance therapy.

AIDS-Related Opportunistic Infections↗
PubMed1992

Effects of epinephrine on insulin-mediated glucose uptake in whole body and leg muscle in humans: role of blood flow.

In vivo insulin-mediated glucose uptake (IMGU) occurs chiefly in skeletal muscle, where it is determined by the product of arteriovenous glucose difference (delta AVG) and blood flow (BF) rate into muscle. Epinephrine (Epi) reduces the rate of IMGU in whole body. To examine whether this is due to a reduction in delta AVG across or BF into skeletal muscle we constructed insulin dose-response curves for whole body IMGU and leg muscle IMGU- using euglycemic clamp ((+)[3-3H]glucose infusion) and leg balance techniques during insulin infusions ranging from 10 to 1,200 mU.m-2.min-1. We studied six subjects [wt 70 +/- 2 (SE) kg] during an Epi infusion at a single rate of 0.002 mg.kg-1.min-1 and six subjects (70 +/- 3 kg) during a saline infusion alone. Maximum whole body glucose uptake (WBGU) was similar during Epi and saline infusions [71.4 vs. 73.6 mmol.kg-1.min-1, P = not significant (NS)]. Compared with saline, maximum delta AVG was decreased during Epi infusion (1.04 vs. 1.31 mM, P less than 0.01). Compared with saline alone maximum leg BF was increased (5.3 vs. 4.3 dl/min, P less than 0.01) during Epi infusion. Thus maximum leg glucose uptake (LGU) was similar (696 vs. 821 pmol.leg-1.min-1, P = NS) during infusion of Epi and saline, respectively. Half-maximal effective dose for insulin's effect to stimulate WBGU, delta AVG, BF, and LGU was increased two- to threefold during Epi vs. saline infusions (P less than 0.01 for all values).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Circulation↗
PubMed1992

Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) exhibit decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Because IMGU is equal to the product of the arteriovenous glucose difference (AVG delta) across and blood flow (F) into muscle (IMGU = AVG delta x F), reduced tissue permeability (AVG delta) and/or glucose and insulin delivery (F) can potentially lead to decreased IMGU. The components of skeletal muscle IMGU were studied in six obese NIDDM subjects (103 +/- 9 kg) and compared with those previously determined in six lean (weight 68 +/- 3 kg), and six obese (94 +/- 3 kg) with normal glucose tolerance. The insulin dose-response curves for whole body and leg muscle IMGU were constructed using the combined euglycemic clamp and leg balance techniques during sequential insulin infusions (range of serum insulin 130-80,000 pmol/L). In lean, obese, and NIDDM subjects, whole body IMGU, femoral AVG delta, and leg IMGU increased in a dose-dependent fashion over the range of insulin with an ED50 of 400-500 pmol/L in lean, 1000-1200 pmol/L in obese, and 4000-7000 pmol/L in NIDDM subjects (P less than 0.01 lean vs. obese and NIDDM). In lean and obese subjects, maximally effective insulin concentrations increased leg blood flow approximately 2-fold from basal with an ED50 of 266 pmol/L and 957 pmol/L, respectively (P less than 0.01 lean vs. obese). In contrast, leg F did not increase from the basal value in NIDDM subjects (2.7 +/- 0.1 vs. 3.5 +/- 0.5 dl/min, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗