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Biomedical subjects

J Bolinder

Publications and source records attributed to J Bolinder.

At least 55 records · Page 3Linked to original sources
PubMed1997

Detection of hypoglycaemia by microdialysis measurements of glucose in subcutaneous adipose tissue.

The aim of the present investigation was to study how various fractional sampling times affect the detection of hypoglycaemia, using microdialysis of the adipose tissue. We therefore studied eight healthy subjects during a standardized hyperinsulinaemic hypoglycaemic clamp. The glucose concentration in the adipose tissue dialysate was determined in timed fractions of 15 min, 30 min and 60 min and compared to those in arterialized venous plasma. Before and after hypoglycaemia, the plasma and adipose tissue glucose concentrations were similar. However, during hypoglycaemia, the adipose tissue glucose nadir, as measured in 15-min fractions of the tissue dialysate, was significantly lower than that in plasma (2.1 +/- 0.1 vs. 2.4 +/- 0.1 mmol/l, p = 0.05) and during the increase in plasma glucose, the corresponding increase in adipose tissue glucose was delayed by approximately 20 min (p = 0.004). When the microdialysate was sampled over 30 or 60 min periods, there was a close agreement between the plasma and adipose tissue glucose nadirs. We conclude that there is a protracted fall in subcutaneous adipose tissue glucose levels in response to insulin-induced hypoglycaemia. While shorter microdialysis sampling periods improve the resolution of the hypoglycaemic event, 30-min fractions seem sufficient to detect hypoglycaemia in a clinically relevant way.

Adipose Tissue↗
PubMed1997

Absolute concentrations of glycerol and lactate in human skeletal muscle, adipose tissue, and blood.

The absolute concentrations of glycerol and lactate were studied with microdialysis of adipose tissue and skeletal muscle in normal-weight subjects. The basal interstitial glycerol concentration was 232 +/- 33, 96 +/- 8, and 59 +/- 6 mumol/l in fat, muscle, and arterialized plasma, respectively (P = 0.0002). This relationship was maintained during both euglycemic hyperinsulinemia, when glycerol decreased in all three compartments, and hypoglycemia, when glycerol first decreased and then increased in fat, muscle, and blood (P = 0.0001 for both). Basal interstitial lactate concentrations were similar in adipose tissue (1.1 +/- 0.2 mmol/l) and skeletal muscle (1.9 +/- 0.4 mmol/l) and higher than in arterialized blood (0.6 +/- 0.1 mmol/l, P = 0.002). During hyperinsulinemia and hypoglycemia, lactate increased (P = 0.0001) and the tissue-blood relationship was maintained (P = 0.04). In conclusion, adipose tissue and skeletal muscle mobilize glycerol and lactate at rest. Glycerol and lactate production are influenced by hyperinsulinemia and hypoglycemia in both tissues. Adipose tissue appears to be the major site of glycerol production, whereas skeletal muscle and fat may be equally important for lactate production.

Adipose Tissue↗
PubMed1997

Self-monitoring of blood glucose in type I diabetic patients: comparison with continuous microdialysis measurements of glucose in subcutaneous adipose tissue during ordinary life conditions.

OBJECTIVE: To evaluate whether frequent self-monitoring of blood glucose (SMBG) sufficiently reflects the true diurnal glucose control during ordinary daily life in type I diabetic patients. RESEARCH DESIGN AND METHODS: By using a microdialysis technique, continuous monitoring of adipose tissue glucose was performed in 24 type I diabetic patients during ambulatory conditions. A microdialysis probe was implanted subcutaneously and perfused by a portable microinfusion pump. Dialysate fractions were collected in 1- to 2-h samples during 3 consecutive days. The diurnal microdialysis glucose profiles were compared with those obtained by SMBG recordings performed seven times a day. RESULTS: In seven patients, the SMBG profiles showed marked aberrations as compared to the continuous microdialysis glucose recordings; during the 3-day study period, 5-6 inconsistencies were registered. In only 4 patients (17%) did SMBG provide a valid reflection (0-2 inconsistencies) of the diurnal glucose profile, whereas in 13 patients the SMBG recordings paralleled the diurnal adipose tissue glucose profiles in an intermediate way (3-4 major inconsistencies). The inaccuracy of the SMBG data was due more often to the fact that wide glucose swings remained unrecognized, rather than to erroneous testing techniques (P < 0.05), and it was more evident during the night (P < 0.05). CONCLUSIONS: In many type I diabetic patients, the true diurnal variability in glycemia is too great to be accurately reflected even by frequent self-monitoring of blood glucose.

Adipose Tissue↗
PubMed1996

Stimulation of adipose tissue lipolysis following insulin-induced hypoglycaemia: evidence of increased beta-adrenoceptor-mediated lipolytic response in IDDM.

The adrenergic regulation of adipose tissue lipolysis in response to insulin-induced hypoglycaemia (intravenous infusion of soluble insulin 0.10 IU.kg body weight-1.h-1 until the arterial plasma glucose fell below 2.8 mmol/l) was investigated directly in vivo in 11 insulin-dependent diabetic (IDDM) patients and 12 control subjects, using microdialysis of the extracellular space of abdominal subcutaneous adipose tissue. The tissue glycerol level (lipolysis index) and the escape of ethanol from the perfusion medium (blood flow index) were continuously monitored. During insulin infusion the arterial glucose level was reduced in parallel and the hypoglycaemic nadir was almost identical in the two groups (diabetic patients 2.2 +/- 0.1 and control subjects 2.3 +/- 0.1 mmol/l). While the maximum response of plasma epinephrine to hypoglycaemia was 30% lower in diabetic patients than in the control subjects (p < 0.05), the glycerol levels in adipose tissue and in plasma, as well as in serum non-esterified fatty acids, increased twice as much in the former as in the latter group following hypoglycaemia (p < 0.01). Addition of the beta-adrenoceptor blocker propranolol (10(4) mol/l) to the tissue perfusate almost completely prevented the hypoglycaemia-induced increase in the adipose tissue glycerol level in both groups, whereas in situ perfusion with 10(-4) mol/l of the alpha-adrenoceptor blocker phentolamine resulted in an additional increase in the tissue glycerol levels; during alpha-blockade, the glycerol response to hypoglycaemia remained enhanced by threefold in the diabetic patients (p < 0.01). In both groups local adipose tissue blood flow increased transiently in a similar way after hypoglycaemia; the increase being inhibited by in situ beta-adrenoceptor blockade. We conclude that both alpha- and beta-adrenergic mechanisms regulate adipose tissue lipolysis in response to hypoglycaemia. In IDDM, lipolysis is markedly enhanced following hypoglycaemia, despite a reduced catecholamine secretory response, because of increased beta-adrenoceptor action in adipose tissue.

Adipose Tissue↗
PubMed1996

Microdialysis of adipose tissue during surgery: effect of local alpha- and beta-adrenoceptor blockade on blood flow and lipolysis.

The adrenergic regulation of adipose tissue lipolysis and blood flow was investigated in nonobese patients (10 men and 23 women) undergoing cholecystectomy. Two microdialysis probes were inserted into the scadipose tissue and microdialyzed in the absence or presence of 10(-4) mol/L of either nonselective beta-adrenoceptor blocker propranolol or nonselective alpha-adrenoceptor blocker phentolamine. The catecholamines increased rapidly after intubation and subsequent surgery and extubation (P = 0.0001; F = 11-13). In the middle of surgery, the elevations of the noradrenaline and adrenaline levels were almost 3 times the basal value. At the end of surgery, they dropped in parallel, but increased again, only to reach their absolute maximum in connection with extubation (10- and 3-fold elevation, respectively). Plasma glycerol and free fatty acids started to increase about 30 min after plasma catecholamines. These increases in catecholamines were paralleled by an increase in the dialysate glycerol level (lipolysis index). Propranolol inhibited by two thirds (P = 0.003) and phentolamine further stimulated by 25% (P = 0.04) the increase in glycerol in the tissue dialysate induced by the operation. There was a transient decrease in tissue blood flow (ethanol escape from the microdialysis probe; P < 0.001) at the beginning of the surgical procedure. This was not affected by propranolol or phentolamine. In conclusion, during anesthesia and surgical trauma, endogenous catecholamines modulate adipose tissue lipolysis via alpha- and beta-adrenoceptors. However, the vasoconstriction induced by these procedures seems to be independent of the adrenergic system.

Adipose Tissue↗
PubMed1996

Evaluation of the microdialysis ethanol technique for monitoring of subcutaneous adipose tissue blood flow in humans.

OBJECTIVE: To investigate the feasibility of the microdialysis ethanol perfusion technique for monitoring nutritive blood flow in subcutaneous adipose tissue. RESEARCH DESIGN AND METHODS: Microdialysis probes were inserted percutaneously into the subcutaneous adipose tissue in 15 non-obese women, and were perfused with 50 mmol/l of ethanol. The experiments were carried out during basal conditions and in conjunction with local vasodilation induced by external heating. The ethanol exchange ratio (ethanol concentration in the outgoing tissue dialysate vs ethanol concentration in the ingoing perfusate) was determined. A comparison was made with the 133Xe clearance technique to assess the adipose tissue blood flow. RESULTS: At rest, the ethanol exchange ratio in the individual subjects was inversely correlated to the adipose tissue blood flow, as measured with 133Xe wash-out (r = -0.78-0.82, p < 0.05-0.01). When the subcutaneous temperature was increased in a stepwise fashion by external heating, adipose tissue blood flow, as determined with 133Xe clearance, was increased by about 50% and 100%, respectively, above resting values (F = 26.7, p < 0.0001). At the same time, the ethanol exchange ratio was progressively and significantly (F = 24.6, p < 0.0001) reduced. In the individual subjects there was a close negative correlation (r = -0.90-0.94) between the ethanol exchange ratios and the corresponding adipose tissue blood flow values, as measured by 133Xe clearance, in response to local vasodilation. CONCLUSION: The microdialysis ethanol perfusion technique provides a valid indicator of small changes within the physiological range in adipose tissue blood flow.

Adipose Tissue↗
PubMed1995

Effect of insulin on renal sodium handling and renal haemodynamics in insulin-dependent (type 1) diabetes mellitus patients.

The effects of insulin on renal haemodynamics and renal sodium handling were studied in eight insulin-dependent (type 1) diabetic patients (aged 30 +/- 3 years). Seven healthy men (aged 38 +/- 4 years) served as controls. The type 1 diabetic patients were resistant to insulin-stimulated glucose disposal as estimated by a 45% lower metabolic (P < 0.01) clearance of glucose as compared with controls. However, type 1 diabetic patients were still sensitive to the distal tubular antinatriuretic effect of insulin, as indicated by an increase in distal sodium reabsorption (95.5 +/- 0.5% to 96.9% +/- 0.4%; P < 0.05) during insulin infusion compared with controls (95.5% +/- 0.6% to 97.4% +/- 0.3%; P < 0.05). In control subjects insulin infusion was associated with 9% increases (P < 0.05) in lithium clearance and in renal plasma flow, whereas no significant increases in lithium clearance and in renal plasma flow were observed in the type 1 diabetic patients. In both groups, the changes in renal plasma flow in response to insulin infusion were positively correlated with that in lithium clearance (r = 0.80 and r = 0.90, respectively; P < 0.05-0.01). In conclusion, the present result demonstrates an intact distal tubular sodium retaining effect in conjunction with a blunted decrease in proximal tubular sodium reabsorption following insulin infusion, which could be the result of an impaired renal vasodilation in type 1 diabetes mellitus.

Adult↗
PubMed1995

Role of phosphodiesterase III in the antilipolytic effect of insulin in vivo.

The effect of three types of phosphodiesterase (PDE) inhibitors on in vivo antilipolysis was investigated in healthy subjects using a 2-h euglycemic, hyperinsulinemic (40 mU.m-2.min) clamp together with microdialysis of abdominal subcutaneous adipose tissue. During hyperinsulinemia (approximately 330 pmol/l), the circulating glycerol concentration was reduced to approximately 50% of the basal level of 53.2 +/- 3.6 mumol/l, indicating an antilipolytic effect. The decrease in adipose tissue dialysate glycerol, which mirrors the change in interstitial glycerol concentration, was about 40% during hyperinsulinemia when Ringer's solution alone was perfused. Local perfusion with a selective PDE IV inhibitor, rolipram (10(-4) mol/l), did not influence the insulin-induced decrease in dialysate glycerol (F = 0.8 vs. perfusion with Ringer's solution by two-factor analysis of variance [ANOVA]), although rolipram increased the dialysate glycerol level by 144 +/- 7% of the baseline value. However, local perfusion with a selective PDE III inhibitor, amrinone (10(-3) mol/l), or a nonselective PDE inhibitor, theophylline (10(-2) mol/l), abolished the ability of insulin to lower dialysate glycerol (F = 16.5, P < 0.01 and F = 8.5, P < 0.01, respectively, as compared with perfusion with Ringer's solution). The findings could not be explained by changes in the local blood flow (as measured by a microdialysis--ethanol escape technique), which was not affected by hyperinsulinemia in the presence or the absence of PDE inhibitors in the dialysis solvent. We conclude that PDEs play an important role in mediating the antilipolytic effect of insulin in vivo and that PDE III is the dominant isoenzyme modulating this effect.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Comparison of bedtime NPH or preprandial regular insulin combined with glibenclamide in secondary sulfonylurea failure.

OBJECTIVE: To compare the effect of bedtime NPH insulin or preprandial regular insulin combined with glibenclamide on metabolic control in non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure to sulfonylurea therapy. RESEARCH DESIGN AND METHODS: Eighty NIDDM patients were randomized to treatment with either three preprandial doses of regular insulin (daytime group D) or a bedtime dose of NPH insulin (nocturnal insulinization, group N), both regimens being combined with 10.5 mg of glibenclamide. Metabolic profiles were obtained at 0, 6, 16 weeks. RESULTS: Glycemic control had improved significantly in both groups after 4 months. Fasting blood glucose was significantly lower compared with baseline in both groups. The mean change +/- SD in group D was -2.8 +/- 3.5 mmol/l and in group N -6.4 +/- 3.0 mmol/L, the reduction being more pronounced in group N compared with group D (P < 0.0001). HbA1c was lowered similarly, from 9.2 +/- 1.4 to 7.1 +/- 1.2% in group D (P < 0.0001) and from 9.1 to 1.1 to 7.5 +/- 1.5% in group N (P < 0.0001). The total daily insulin doses were similar, 29 +/- 11 U in group D and 26 +/- 9 U in group N, and the circulating insulin levels during daytime were higher in group D than in group N. Total serum cholesterol and triglycerides were similarly and significantly lowered compared with baseline in both groups. Weight gain was more pronounced in group D (3.4 +/- 0.3 kg) than in group N (1.9 +/- 1.9 kg; D vs. N, P < 0.002), and the change was inversely correlated with initial eight but not with the improvement in HbA1c. CONCLUSIONS: The two insulin regimens exert similar effect on glucose metabolism and serum lipids in NIDDM patients on combination therapy. Weight gain is more pronounced in patients given insulin during the daytime when preprandial doses of short-acting insulin are used.

Adult↗
PubMed1995

Influence of local blood flow on glycerol levels in human adipose tissue.

DESIGN: The influence of blood flow on adipose tissue glycerol levels was investigated in human subcutaneous adipose tissue in situ, with the aid of microdialysis of the extracellular water space. The concentration of tissue-derived glycerol and the escape of ethanol from the dialysis solvent into the extracellular space were simultaneously monitored; the latter was used as an index of local blood flow around the probe. RESULTS: Selective vasodilation with nitroprusside or hydralazine rapidly reduced the concentration of glycerol by 50% and at the same time increased the escape of ethanol (P < 0.001). Stimulation of local blood flow and lipolysis with the beta-adrenoceptor agonist isoprenaline caused an increase in ethanol escape (P = 0.01) and a 100% rise in the dialysate glycerol level (P = 0.001). When vasodilation was first induced by nitroprusside, the subsequent addition of isoprenaline to the microdialysate perfusate caused no change in the concentration of glycerol in adipose tissue but a slight increase in ethanol escape. CONCLUSIONS: In conclusion, local blood flow plays an important role in the regulation of the glycerol level in human adipose tissue. Stimulation of blood flow may under certain conditions decrease the level of glycerol in the extracellular space of adipose tissue although the mobilization of glycerol from fat cells to this compartment is increased. Thus, changes in blood flow and glycerol should be considered together when adipose tissue lipolysis is investigated by microdialysis.

Adipose Tissue↗
PubMed1994

Transplantation of porcine fetal pancreas to diabetic patients.

Transplantation of fetal porcine islet-like cell clusters (ICC) reverses diabetes in experimental animals. We have now transplanted porcine ICC to ten insulin-dependent diabetic kidney-transplant patients. All patients received standard immunosuppression and, at ICC transplantation, antithymocyte globulin or 15-deoxyspergualin. ICC were injected intraportally or placed under the kidney capsule of the renal graft. Four patients excreted small amounts of porcine C-peptide in urine for 200-400 days. In one renal-graft biopsy specimen, morphologically intact epithelial cells stained positively for insulin and glucagon in the subcapsular space. We conclude that porcine pancreatic endocrine tissue can survive in the human body.

Adult↗
PubMed1994

Lipolytic and cardiac responses to various forms of stress in humans.

The lipolytic and the cardiac responses to 30 min of two different forms of stress--a standardized mental stress test and submaximal bicycle exercise--were investigated in non-obese healthy subjects. This was done by microdialysis of the extracellular space in the abdominal subcutaneous adipose tissue in order to determine lipolysis and electrocardiographic recordings of the heart rate. Glycerol concentrations (lipolysis index) in venous plasma and in adipose tissue dialysate as well as plasma catecholamines and determinations of the heart rate showed marked increases during mental stress (p < 0.001) and physical exercise (p < 0.001), but the patterns of response differed during the two forms of stress. All parameters rose gradually during exercise and decreased continuously in the post-exercise period. During mental stress, however, all parameters peaked within the first 20 min of stimulation and then remained at the same level until after the stress period, when they gradually declined. The maximal increase of glycerol in plasma and adipose tissue during mental stress correlated with the corresponding increase during exercise (r = 0.50-0.60). Such a relationship was not observed with plasma catecholamines or heart rate (r = 0.02-0.29). The peak level of plasma noradrenaline was an independent regressor for the peak levels of glycerol in plasma and adipose tissue as well as for the peak heart rate during mental stress and physical exercise (partial r from 0.35 to 0.64), while the peak level of adrenaline was a regressor for heart rate only during mental stress (partial r = 0.45), when multiple regression analysis was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗