Decreased permeability surface area for glucose in obese women with postprandial hyperglycemia: no effect of phosphodiesterase-5 (PDE-5) inhibition.

Insulin-mediated microvascular recruitment is recognized as a potential mechanism contributing to insulin resistance. In this study, we compared a marker of microvascular function, the permeability surface area for glucose (PS(glu)), and forearm glucose uptake after an OGTT in obese women with impaired glucose metabolism and healthy lean nondiabetic women, with the aim to characterize whether decreased permeability surface area for glucose or decreased glucose uptake may contribute to postprandial hyperglycemia in the obese group. In addition, we evaluated whether the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, in a randomized double blind placebo controlled design, might attenuate postprandial glucose levels in obese women.

The selective phosphodiesterase-5 inhibitor tadalafil induces microvascular and metabolic effects in type 2 diabetic postmenopausal females.

Objective: The objective of the study was to explore the acute in vivo effects of the selective phosphodiesterase-5 inhibitor tadalafil on local microcirculation and regional metabolism in skeletal muscle and adipose tissue (AT).

Design, Setting, And Participants: We studied eight postmenopausal female patients with type 2 diabetes (T2D) and eight nondiabetic controls (Ctrl) in the postabsorptive state and 180 min after the administration of tadalafil 10 mg. Intramuscular and sc microdialysis were combined with measurements of forearm (FBF) and AT blood flow as well as with arterial and deep venous blood sampling.

Impaired delivery of insulin to adipose tissue and skeletal muscle in obese women with postprandial hyperglycemia.

Context: An impaired transfer of insulin from the circulation to the interstitial fluid has been suggested to contribute to insulin resistance.

Objective: The objective of the study was to address whether the delivery of insulin from the circulation to adipose tissue and skeletal muscle is impaired in obese women with postprandial hyperglycemia compared with lean healthy controls.

Design, Setting, And Participants: Seven obese nondiabetic women with postprandial hyperglycemia and nine lean healthy women were recruited.

Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes.

Aims/hypothesis: Recent evidence suggests that reduced synthesis of nitric oxide in endothelial cells, i.e. endothelial dysfunction, contributes to the impaired action of insulin in the vasculature of patients with type 2 diabetes.

Myocardial metabolism assessed by microdialysis: a prospective randomized study in on- and off-pump coronary bypass surgery.

Objective: The aim of the study was to compare energetic metabolism in the myocardium during coronary surgery with and without cardiopulmonary bypass by means of microdialysis.

Methods: Twenty-six low-risk patients were prospectively randomized to off-pump versus on-pump surgery. Microdialysis was used to sample myocardial interstitial fluid during and for 23 hours after surgery.

Effects of Intrabrachial metacholine infusion on muscle capillary recruitment and forearm glucose uptake during physiological hyperinsulinemia in obese, insulin-resistant individuals.

Context: Impairment of insulin-mediated capillary recruitment in skeletal muscle contributes to a hampered glucose uptake in obesity.

Objective: The objective of this study was to evaluate whether metacholine (MCh), a nitric oxide vasodilator, potentiates muscle capillary recruitment and forearm glucose uptake (FGU) during physiological hyperinsulinemia.

Design: The double-forearm technique [i.

Cyclic adenosine monophosphate-phosphodiesterase inhibitors reduce skeletal muscle protein catabolism in septic rats.

We have previously shown that catecholamines exert an inhibitory effect on muscle protein degradation through a pathway involving the cyclic adenosine monophosphate (cAMP) cascade in normal rats. In the present work, we investigated in vivo and in vitro effects of cAMP-phosphodiesterase inhibitors on protein metabolism in skeletal muscle from rats submitted to a model of acute sepsis. The in vivo muscle protein metabolism was evaluated indirectly by measurements of the tyrosine interstitial concentration using microdialysis.

Microdialysis for myocardial metabolic surveillance: developing a clinical technique.

Metabolic surveillance of the myocardium is of great interest in cardiac surgery. Microdialysis allows sampling of chemical substances from the interstitial fluid for immediate analysis. The two objectives of this study were to develop a technique for simple and safe implantation of a commercially available microdialysis probe (CMA-70) into the myocardium and to obtain reference data for further use and metabolic control.

Laser-Doppler flowmetry reveals rapid perfusion changes in adipose tissue of lean and obese females.

The present study aimed to evaluate adipose tissue blood flow (ATBF) by means of laser-Doppler flowmetry (LDF) in humans. Lower body negative pressure (LBNP) and straining known to affect epidermal blood flow through the autonomic nervous system were performed in 11 lean and 11 obese female volunteers. ATBF changes were compared between both groups and also discriminated from skin blood flow (SBF) responses of the immediate vicinity.

Increased fat mass compensates for insulin resistance in abdominal obesity and type 2 diabetes: a positron-emitting tomography study.

To evaluate the relative impact of abdominal obesity and newly diagnosed type 2 diabetes on insulin action in skeletal muscle and fat tissue, we studied 61 men with (n = 31) or without (n = 30) diabetes, subgrouped into abdominally obese or nonobese according to the waist circumference. Adipose tissue depots were quantified by magnetic resonance imaging, and regional glucose uptake was measured using 2-[(18)F]fluoro-2-deoxyglucose/positron emission tomography during euglycemic hyperinsulinemia. Across groups, glucose uptake per unit tissue weight was higher in visceral (20.

Delayed transcapillary delivery of insulin to muscle interstitial fluid after oral glucose load in obese subjects.

Obese subjects exhibit a delay in insulin action and delivery of insulin to muscle interstitial fluid during glucose/insulin infusion. The aim of the present study was to follow the distribution of insulin to skeletal muscle after an oral glucose load in obese subjects. We conducted an oral glucose tolerance test (OGTT) in 10 lean and 10 obese subjects (BMI 23 +/- 0.

Decreased muscle capillary permeability surface area in type 2 diabetic subjects.

Capillary recruitment in muscles, induced by insulin, has been proposed to be impaired in insulin-resistant states. To elucidate the mechanisms regulating capillary transport of insulin and glucose in type 2 diabetes, we directly calculated the permeability-surface area product (PS) for glucose and insulin in muscle. Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in type 2 diabetic male subjects and age- and weight-matched controls during a euglycemic-hyperinsulinemic clamp.

Regulation and counterregulation of lipolysis in vivo: different roles of sympathetic activation and insulin.

To obtain further information on the regulation of lipolysis in vivo, the effect of increasing sympathetic nerve activity via lower body negative pressure (LBNP, -20 mm Hg) was studied in 11 healthy human subjects. Subcutaneous and muscle microdialysis as well as blood flow measurements were performed in the postabsorptive state and during an euglycemic hyperinsulinemic clamp. LBNP for 30 min in the postabsorptive phase resulted in an approximately 50% increase (P < 0.

Direct measurements of the permeability surface area for insulin and glucose in human skeletal muscle.

To elucidate mechanisms regulating capillary transport of insulin and glucose, we directly calculated the permeability surface (PS) area product for glucose and insulin in muscle. Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in healthy males, studied during an oral glucose tolerance test or during a one-step or two-step euglycemic hyperinsulinemic clamp. PS for glucose increased significantly from 0.

Sympathetic control of white adipose tissue in lean and obese humans.

Aim: To induce lipolysis, catecholamines could reach the adipocyte via the blood stream after being released from the adrenal medulla or, alternatively, via neuronal release in the vicinity of the fat cell. Sympatho-neuronal effects on fat tissue lipolysis have been demonstrated in experimental animal models. However, the role of sympathetic nerves in the control of lipolysis in human white adipose tissue, which is sparsely innervated, has not been clarified.

Validation of a glucose-insulin-potassium infusion algorithm in hospitalized diabetic patients.

Objectives: Validation of a novel glucose-insulin-potassium (GIK) infusion algorithm to optimize metabolic control in hospitalized diabetic patients.

Subjects: We randomized 33 diabetic patients admitted to Sahlgrenska University Hospital with acute internal medicine diseases to either GIK infusion or multiple injection therapy (MIT). The GIK infusion rate and the MIT were controlled according to special algorithms.

Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects.

We evaluated the effects of rosiglitazone (4 mg b.i.d.

Intramyocardial troponin-T monitoring with microdialysis in coronary artery bypass surgery.

Objective: To investigate the time course of troponin-T release into the extracellular fluid of the myocardium and to distinguish between a rise in troponin-T due to implantation trauma and an increase due to cardiac arrest during coronary surgery.

Design: Microdialysis probes were implanted in the heart of seven patients soon after sternotomy. Troponin-T was measured in the microdialysates and in peripheral blood from 3 h before to 24 h after heart arrest.

Myocardial interstitial glucose and lactate before, during, and after cardioplegic heart arrest.

The interstitial fluid of the human myocardium was monitored in 13 patients undergoing aortic valve and/or bypass surgery before, during, and after hypothermic potassium cardioplegia. The regulation of glucose and lactate was studied after sampling with microdialysis. The following questions were addressed.

Delayed transcapillary transport of insulin to muscle interstitial fluid in obese subjects.

Insulin-resistant subjects have a slow onset of insulin action, and the underlying mechanism has not been determined. To evaluate whether a delayed transcapillary transport is part of the peripheral insulin resistance, we followed the kinetics of infused insulin and inulin in plasma and muscle interstitial fluid in obese insulin-resistant patients and control subjects. A total of 10 lean and 10 obese men (BMI 24 +/- 0.

Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans.

To elucidate the role of adipose tissue glucose uptake in whole-body metabolism, sc and visceral adipose tissue glucose uptake and perfusion were measured in 10 nonobese and 10 age-matched obese men with positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose, and [(15)O]-labeled water during normoglycemic hyperinsulinemia. Whole-body and skeletal muscle glucose uptake rates per kilogram were lower in obese than in nonobese subjects (P < 0.01).

Measurements of interstitial muscle glycerol in normal and insulin-resistant subjects.

The aim of this project was to study the regulation of interstitial glycerol levels in muscle in normal subjects, and to estimate interstitial muscle glycerol in obese subjects and patients with type 2 diabetes. In healthy lean subjects, microdialysis of forearm sc and muscle tissue were combined with arterial and deep venous catheterization, as well as blood flow registrations during oral glucose ingestion. In two other separate studies, obese (n = 9) vs.

Involuntary leg movements affect interstitial nutrient gradients and blood flow in rat skeletal muscle.

To evaluate the effect of passive muscle shortening and lengthening (PSL) on the transcapillary exchange of glucose, lactate, and insulin in the insulin-stimulated state, microdialysis was performed in rat quadriceps muscle. Electrical pulsatile stimulation (0.1 ms, 0.

Human adipose tissue glucose uptake determined using [(18)F]-fluoro-deoxy-glucose ([(18)F]FDG) and PET in combination with microdialysis.

Aims/hypothesis: To determine the lumped constant (LC), which accounts for the differences in the transport and phosphorylation between [(18)F]-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) and glucose, for [(18)F]FDG in human adipose tissue.

Methods: [(18)F]FDG-PET was combined with microdialysis. Seven non-obese (29 +/- 2 years of age, BMI 24 +/- 1 kg/m2) and seven obese (age 32 +/- 2 years of age, BMI 31 +/- 1 kg/m2) men were studied during euglycaemic hyperinsulinaemia (1 mU/kg.