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Biomedical subjects

J Bolinder

Publications and source records attributed to J Bolinder.

At least 73 records · Page 4Linked to original sources

Lipolysis during abdominal surgery.

Subcutaneous adipose tissue lipolysis has been monitored with microdialysis during elective cholecystectomy by laparotomy in otherwise healthy nonobese subjects. Eight of the subjects received saline and seven received glucose iv during the operation. In both groups the glycerol level in the microdialysate (lipolysis index) started to increase steadily from the start of the general anesthesia until the abdominal wall was closed. Thereafter it leveled off and remained elevated until after extubation. Plasma glycerol started to rise after the surgical incision. The levels of noradrenaline and adrenaline, but not of insulin, glucagon, and cortisol in plasma, changed in parallel with that of glycerol in the microdialysate. The glycerol response in adipose tissue in the group receiving iv glucose was three times more marked than in the saline group (P = 0.01) in spite of marked hyperinsulinemia, but there was no difference between the groups in plasma glycerol response. The plasma noradrenaline response was 50% higher (P = 0.03) in the glucose group than in the saline group, but there was no difference between the groups in the plasma adrenaline, glucagon, or cortisol responses. Adipose tissue blood flow was measured by the escape of ethanol from the dialysis solvent into the extracellular space. It was constant throughout the experimental period in both groups. In conclusion, the lipolysis rate is accelerated during general anesthesia and abdominal surgery because of increased catecholamine production. Perioperative glucose infusion is associated with a further acceleration of the lipolytic rate in subcutaneous adipose tissue due to an additional activation of the sympathetic nervous activity that overrides the antilipolytic effect of the glucose-induced hyperinsulinemia. Other adipose regions may be less sensitive to glucose infusions and anesthesia.

Adipose Tissue↗

Influence of operation on glucose metabolism and lipolysis in human adipose tissue: a microdialysis study.

OBJECTIVE: To investigate the effect of an operation on metabolism in human adipose tissue. DESIGN: Open study. SETTING: Department of Surgery and the Research Centre at Huddinge Hospital. SUBJECTS: 13 non-obese patients who underwent elective cholecystectomy, and 5 control subjects. INTERVENTIONS: Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was done before, during and after a 45-minute intravenous infusion of 20 g glucose before, and one day after, the operation. MAIN OUTCOME MEASURES: Concentrations of glycerol, glucose, lactate and pyruvate in the tissue dialysate and in venous plasma. RESULTS: After operation, the baseline plasma insulin concentration doubled (p < 0.001) and the fasting glucose concentration rose from 4.4 (0.1) to 5.3 (0.2) mmol/l (p < 0.001). In response to the glucose infusion, the maximum increase in plasma insulin trebled (p < 0.01) and the integrated concentrations (area under the curve) of plasma glucose, lactate and pyruvate were significantly more pronounced (p < 0.02-p < 0.001) after than before operation. The suppression of plasma glycerol and free fatty acid concentrations was similar before and after operation (50-60%). The reduction in the concentrations of glycerol in adipose tissue, and the increases in the concentrations of glucose, lactate, and pyruvate, after intravenous infusion of glucose were not influenced by the operation. CONCLUSION: A moderately serious operation rapidly induces a deterioration in total body glucose homeostasis, partly as a result of peripheral insulin resistance. This does not affect the utilization of glucose by adipose tissue or the antilipolytic response to glucose infusion.

Adipose Tissue↗

Long-term continuous glucose monitoring with microdialysis in ambulatory insulin-dependent diabetic patients.

The glucose concentration in the extracellular space of subcutaneous adipose tissue closely mirrors the blood glucose concentration. With a microdialysis technique, we undertook continuous ambulatory monitoring of adipose tissue glucose in 17 insulin-dependent diabetic patients with labile glycaemic control. The aims of the study were to investigate performance of the microdialysis device and to evaluate whether consecutive 24 h glucose profiles could be used to adjust insulin therapy. A microdialysis probe was implanted subcutaneously, perfused by a portable microinfusion pump, and dialysate fractions were collected every 1 or 2 h for 75 h. The mean (SE) tissue dialysate glucose concentration was 93 (3)% of the concentration in venous plasma, and variations in adipose tissue glucose closely paralleled changes in plasma glucose. Mean 24 h tissue glucose concentration correlated significantly with glycosylated haemoglobin (HbA1c; r = 0.62, p < 0.01). Most patients had a reproducible daily pattern of glucose swings, and in more than half the patients consecutive ambulatory glucose profiles were almost superimposed. When patients' insulin therapy was adjusted on the basis of ambulatory glucose monitoring, HbA1c decreased by almost 2% (p < 0.01), and this decrease lasted for at least 9 months. Microdialysis of adipose tissue can be used for continuous long-term monitoring of glucose concentrations in diabetic patients during ordinary daily life. Daily glucose profiles are often reproducible and the recordings may thus be used for individual tailoring of insulin therapy to improve glycaemic control.

Adipose Tissue↗

Influence of insulin on glucose metabolism and lipolysis in adipose tissue in situ in patients with liver cirrhosis.

The influence of insulin on lipolysis and glucose metabolism in abdominal adipose tissue was studied in situ with the microdialysis technique during a euglycaemic insulin clamp (1 mU kg-1 min-1) in nine cirrhotic patients and 10 controls. The cirrhotic patients displayed a 50% decrease in glucose utilization rate during the clamp (P < 0.001). Dialysate glucose levels decreased similarly by 20-30%., in patients and controls, which in the presence of unchanged local blood flow in the adipose tissue in response to insulin, is at hand with a glucose uptake into the adipocytes of similar magnitude in both groups. Before and during the clamp, the arterial and dialysate levels of glycerol were higher in the patients than in the control subjects (ANOVA P = 0.001 and 0.048 in arterial blood and dialysate, respectively). In relative terms, however, insulin induced a 70% reduction of arterial and dialysate glycerol in both groups. The concentrations of lactate and pyruvate in the dialysate and blood increased in a similar way in both groups during hyperinsulinaemia. The results suggest an increased rate of lipolysis in cirrhotic patients. Insulin cannot lower it to normal, although it is still capable of achieving a relative reduction. No explanation was found in the adipose tissue to the insulin resistance to whole-body glucose utilization that was noted in the patients with cirrhosis.

Adipose Tissue↗

Adrenergic regulation of human adipose tissue metabolism in situ during mental stress.

The adrenergic regulation of adipose tissue lipolysis and glucose metabolism was investigated in situ during a standardized mental stress test in 11 nonobese, healthy subjects, using microdialysis of the extracellular water space in sc adipose tissue. Microdialysis probes were inserted in the abdominal sc fat, and were perfused using solvents with or without adrenoceptor blocking agents. The tissue dialysate concentrations of glycerol (lipolysis index) glucose, lactate, and pyruvate were determined. The glycerol concentration in adipose tissue increased markedly during the stress test and decreased in the poststress period. A similar kinetic pattern was observed in blood. In situ administration of the nonselective beta-adrenoceptor blocking agent propranolol almost completely prevented the stress-induced increase in adipose tissue glycerol levels, whereas a nonselective alpha-adrenoceptor blocking agent (phentolamine) was ineffective in this respect. Plasma levels of glucose and lactate remained unaltered during and after the stress test; at the same time plasma pyruvate decreased moderately. By contrast, glucose, lactate, and pyruvate in adipose tissue increased by 25-30% during or after the stress (P < 0.05). The increase in lactate and pyruvate in adipose tissue after the stress was completely off-set by alpha-adrenoceptor blockade in situ, whereas beta-adrenoceptor blockade in situ did not influence the kinetic pattern of these metabolites. It is concluded that the lipolytic activity in human adipose tissue is markedly enhanced during mental stress, owing to adrenergic mechanisms that are mediated via beta-adrenoceptors. After mental stress, adipose tissue glucose utilization is decreased and routed toward nonoxidative pathways. The latter seems to involve adrenergic effects that are mediated via alpha-adrenoceptors.

Adipose Tissue↗

Effect of phosphodiesterase inhibition with amrinone or theophylline on lipolysis and blood flow in human adipose tissue in vivo as measured with microdialysis.

Phosphodiesterase III (cyclic GMP-inhibited, particulate, low Km) is believed to play a dominant role in the cyclic AMP breakdown and lipolysis regulation in fat cells. Its importance for lipolysis activity was investigated in situ in humans by comparing the effects of a selective (amrinone) and a nonselective (theophylline) inhibitor of the enzyme. Abdominal subcutaneous adipose tissue of healthy nonobese humans was microdialyzed with solvents containing one or both of these agents, and glycerol (lipolysis index) or the escape of ethanol from the dialysis solvent (blood flow index) was continuously monitored in the perfusate. Both agents caused a dose-dependent and sustained increase in the glycerol level in the perfusate for at least 2.5 h. Although amrinone was 5000 times more potent than theophylline on a molar basis, its maximum activity was only 35% as compared to the maximum activity of theophylline. Half-maximum lipolytic effect of the two drugs occurred at about 0.1 mumol/l and 1 mmol/l, respectively (P < 0.001). At maximum effective concentrations, amrinone stimulated lipolysis by about 63% and theophylline by about 200% (P < 0.01). At these concentrations amrinone increased the rate of disappearance of ethanol from the perfusate by about 20% and theophylline increased the rate by about 75%, the difference being statistically significant (P < 0.01). When the two drugs were added together, the level of lipolysis stimulation was not different from that with theophylline alone both at maximal and submaximal effective concentrations of drug combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors.

The effects of insulin, and its interactions with catecholamines through beta-adrenoceptors, on human adipose tissue glucose utilization and lipolysis were investigated in vivo. Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was performed in healthy subjects of normal weight, before and during a 2-h hyperinsulinaemic (61 +/- 3 mU/l), euglycaemic clamp. The tissue was perfused with or without the beta-adrenergic agonist isoproterenol (10(-6) mol/l), and the tissue dialysate concentrations of glucose, glycerol (lipolysis index) lactate and pyruvate were determined. During the insulin infusion, glucose in adipose tissue decreased by 20% (p less than 0.001), despite arterial steady-state normoglycaemia. The concentrations of lactate and pyruvate increased gradually to a steady-state plateau of twice the basal level in adipose tissue and arterial blood. Insulin-induced suppression of glycerol (lipolysis index) was, if anything, more marked in adipose tissue than in plasma (65% vs 50% decrease from baseline levels, p less than 0.05). In situ perfusion of adipose tissue with isoproterenol, starting either at the beginning of the study period or at 45 min after initiation of the insulin infusion, resulted in marked and rapid elevations of all the investigated metabolites in the adipose tissue extracellular compartment (p less than 0.05-0.005). It is concluded that insulin action on glucose uptake and lipolysis in human adipose tissue in vivo is counteracted by beta-adrenoceptor stimulation. In contrast, insulin and beta-adrenoceptors have synergistic effects on non-oxidative glucose metabolism in human adipose tissue in situ.

Adipose Tissue↗

Microdialysis measurement of the absolute glucose concentration in subcutaneous adipose tissue allowing glucose monitoring in diabetic patients.

The possibility of continuously monitoring the absolute glucose concentration in subcutaneous adipose tissue, using microdialysis of the extracellular water space, was investigated in six Type 1 (insulin-dependent) diabetic patients. By using a large microdialysis probe (30 x 0.62 mm), and by perfusing with a low flow rate (0.5 microliters/min), complete recovery of glucose was attained in vitro. In the patients the dialysis probe was implanted subcutaneously, perfused by a wearable microinfusion pump, and dialysate samples were collected in 60-min fractions over 10 h. The absolute glucose concentration in the tissue dialysate was the same or almost the same as the blood glucose concentration (range 87-101% of the blood glucose value). The changes in blood glucose were closely paralleled by the variations in adipose tissue glucose (r = 0.93, p < 0.01), and the recovery of glucose in the microdialysate remained constant during the 10-h study period. In conclusion, it is possible, using microdialysis, to directly determine the absolute glucose concentration in subcutaneous adipose tissue. Hence, this technique may be used for continuous glucose monitoring in diabetic patients.

Adipose Tissue↗

Effects of insulin on renal haemodynamics and the proximal and distal tubular sodium handling in healthy subjects.

The effects of insulin on renal haemodynamics and renal sodium handling were studied in 10 healthy males. Using the euglycaemic insulin clamp technique, insulin was infused on separate days resulting in two levels of hyperinsulinaemia (41 +/- 3 and 90 +/- 7 mU/l, respectively). Renal haemodynamics and the proximal and distal tubular sodium handling were studied using inulin, para-amino-hippuric acid, sodium and lithium clearances. Low- and high-dose insulin infusions were followed by a fall in sodium clearance from 1.6 +/- 0.1 ml/min to 1.2 +/- 0.1 and 1.0 +/- 0.1 ml/min, respectively. Both levels of hyperinsulinaemia resulted in increased distal tubular sodium reabsorption. The distal antinatriuretic effect of insulin was associated with dose- and time-dependent decline in proximal tubular sodium reabsorption. The changes in proximal tubular sodium handling occurred without any significant changes in natriuretic factors, such as renal dopamine and plasma atrial natriuretic peptide levels. However, hyperinsulinaemia resulted in time- and dose-dependent increases in renal plasma flow, and renal vasodilatation could, possibly via changes in renal interstitial pressure, have contributed to the fall in the proximal tubular sodium reabsorption. The results also suggest that decreased proximal sodium reabsorption may be a compensatory mechanism counteracting the insulin-induced sodium retention.

Adult↗

Impaired intrarenal dopamine production following intravenous sodium chloride infusion in type 1 (insulin-dependent) diabetes mellitus.

Type 1 (insulin-dependent) diabetes mellitus is characterized by impaired sodium excretion following NaCl infusion. To investigate the possible role of dopamine in the impaired natriuresis in diabetes, intrarenal sodium handling, sodium excretion and urinary dopamine output, reflecting intrarenal dopamine formation, were studied following a 2 h 0.9% NaCl infusion (25 ml/kg) in eight diabetic patients and nine control subjects. The increase in sodium excretion in response to NaCl infusion was significantly (p less than 0.01) reduced in diabetic patients (19 +/- 7%) as compared with control subjects (46 +/- 8%). Fractional proximal tubular sodium reabsorption (determined by lithium clearance) decreased in the control group (p less than 0.01) following NaCl infusion but not in the diabetic group. Fractional distal tubular reabsorption decreased similarly in both groups. In response to NaCl urinary dopamine excretion increased by approximately 15% (p less than 0.01) in the control group but did not change in the diabetic group. The mean urinary dopamine excretion above basal was significantly greater in the control group (8.4 +/- 2.1 nmol/h) than in the diabetic group (-2.2 +/- 2.1 nmol/h; p less than 0.01). The urinary sodium/dopamine excretion ratio did not differ significantly between the two groups in the basal state or following NaCl. Baseline plasma levels of atrial natriuretic peptide did not differ between control and diabetic patients. In the control group atrial natriuretic peptide levels increased significantly (p less than 0.01) in response to NaCl whereas atrial natriuretic peptide levels did not change in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗