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G Boden

Publications and source records attributed to G Boden.

At least 73 records · Page 4Linked to original sources
PubMed1993

Insulin binding and degradation by rat liver Kupffer and endothelial cells.

The liver is the major site of insulin metabolism. Previous studies have suggested that hepatocytes were chiefly responsible for this activity, while contributions of Kupffer and other nonparenchymal liver cells remained controversial. In this study, we compared 125I-insulin binding and degradation by rat hepatocytes with insulin binding and degradation by sinusoidal Kupffer and endothelial cells. Kupffer cells were separated from endothelial cells by centrifugal elutriation. Hepatocytes had approximately 3.5 times more insulin binding sites than Kupffer cells and approximately eight times more binding sites than endothelial cells. In addition, wheat germ agglutinin (WGA)-purified solubilized receptors from all three cell types bound insulin in proportions similar to whole cells. Moreover, all three cell types were shown with a ribonuclease (RNase) protection assay to express insulin receptor mRNA. Hepatocytes degraded approximately four times more insulin than Kupffer cells, while endothelial cells degraded only negligible amounts of insulin. Based on morphometric data available in the literature, we estimated that nonparenchymal cells could account for approximately 10% to 15% of hepatic insulin degradation. We concluded that rat hepatocytes, Kupffer cells, and endothelial cells all have specific insulin receptors, and that nonparenchymal cells play a small but significant role in insulin degradation.

Animals↗
PubMed1993

Evidence that suppression of insulin secretion by insulin itself is neurally mediated.

We examined the mechanism by which an increase in blood insulin concentration inhibits insulin secretion by the pancreas. To this end, we determined plasma C-peptide concentrations during euglycemic-hyperinsulinemic (approximately 500 pmol/L) clamps in five patients with insulin-dependent diabetes mellitus (IDDM) after combined pancreas and kidney (P/K) transplantation, in five nondiabetic patients after kidney transplantation (K), and in six normal control subjects. Hyperinsulinemia decreased C-peptide concentrations in K patients (by 60%, P < .01) and controls (by 35%, P < .05), but not in P/K patients (653 +/- 115 v 702 +/- 197 pmol/L before and after 4 hours of hyperinsulinemia, respectively). The main difference between K patients and controls and P/K patients was that the pancreas in K patients and controls was innervated, whereas the transplanted pancreas of K/P patients was denervated. The data therefore suggested that the inhibition of pancreatic insulin secretion by hyperinsulinemia was neurally mediated.

Adult↗
PubMed1993

A novel therapy for atopic dermatitis with allergen-antibody complexes: a double-blind, placebo-controlled study.

BACKGROUND: Exposure to airborne allergens exacerbates symptoms of atopic dermatitis (AD) in hypersensitive patients. OBJECTIVE: Our purpose was to determine whether the administration of allergen-antibody complexes would improve the symptoms of AD. METHODS: Twenty-four adults with AD and hypersensitivity to Dermatophagoides pteronyssinus (Dpt) were treated in a double-blind, placebo-controlled trial by intradermal injections of complexes containing autologous specific antibodies and Dpt allergens. After 4 months, placebo-treated patients started receiving active treatment. All patients were treated for a full year. Clinical status and Dpt-specific IgG and IgE antibody levels were monitored. RESULTS: Symptoms of AD subsided within a few weeks after starting therapy, with significant reduction after 4 months in treated patients only. After 1 year, 82% of the patients exhibited a mean improvement of 83%, associated with reduction of Dpt-specific IgG antibodies. CONCLUSION: The treatment of Dpt-sensitive patients with AD by injections of allergen-antibody complexes is safe and effective in a majority of patients.

Adolescent↗
PubMed1993

Ethanol inhibits insulin action on lipolysis and on insulin release in elderly men.

We have studied effects of ethanol on insulin's ability to suppress its own release and on its antilipolytic action in 12 healthy elderly men during euglycemic hyperinsulinemia. Insulin secretion was estimated from plasma C-peptide concentrations. Lipolysis was determined with the two stable isotopes [2H5]glycerol and [1-13C]palmitate. Hyperinsulinemia (approximately 350 pM) decreased plasma C-peptide by approximately 60% (from 325 to 122 pM, P < 0.05). Ethanol (approximately 10 mM) completely prevented the fall in C-peptide concentration. Ethanol decreased the antilipolytic action of insulin by approximately 40% [with insulin alone, glycerol rate of appearance (Ra) decreased from 1.8 to 0.6 mumol.kg-1 x min-1; with insulin + ethanol, it only decreased from 1.8 to 1.1 mumol.kg-1 x min-1]. Ethanol did not affect palmitate Ra, which fell from 1.4 to 0.6 mumol.kg-1 x min-1 with insulin and from 1.4 to 0.3 mumol.kg-1 x min-1 with insulin plus ethanol. Fatty acid reesterification was not affected by insulin but tripled (from 0.6 to 1.9 mumol.kg-1 x min-1) in response to insulin plus ethanol. Our data showed that modest concentrations of ethanol suppressed the inhibitory actions of insulin on its own release and on lipolysis. The inhibition by ethanol of various insulin actions, including glucose disposal, lipolysis, and insulin release, in diverse tissues such as muscle, adipose tissue, and pancreas raises the possibility that ethanol may produce a state of generalized insulin resistance.

Aged↗
PubMed1993

Quantitation of glycolysis and skeletal muscle glycogen synthesis in humans.

We measured the net rates of skeletal muscle glycogen synthesis and glycolysis (conversion of [3-3H]glucose to 3H2O) in healthy overnight-fasted volunteers. Two studies were performed. In study 1, seven subjects participated in two paired infusions under basal conditions of either [2-3H]glucose (H2) or [3-3H]glucose (H3). Total glucose uptake (Rd) and rates of whole body 3H2O formation (3H2O Ra) were measured. With H2, Rd and 3H2O Ra were similar. With H3, 3H2O Ra, equal to glycolysis, was 65% of Rd. In study 2, six different subjects underwent a 3-h, 40 mU.m-2 x min-1 euglycemic insulin clamp. [6,6-2H2]glucose was infused throughout and H3 was infused during the last hour of the study. Open muscle biopsies were obtained at 150 and 180 min. Glycogen synthesis was assessed by three independent means: 1) direct measurement, as 3H disintegrations per minute in isolated muscle glycogen per plasma H3 specific activity; 2) extrapolation from the activity of glycogen synthase assayed in the presence of the concentrations of glucose 6-phosphate and UDP-glucose measured in the biopsy; and 3) the difference between Rd and glycolysis. Despite a wide range in Rd [24.5-58.8 mumol.kg fat-free mass (FFM)-1 x min-1] and glycolysis (14.2-26.1), the three methods yielded similar results of 20.0 +/- 3.9, 22.5 +/- 3.7, and 20.6 +/- 3.7 mumol.kg FFM-1 x min-1 and correlated highly with each other (r2 = 0.92-0.96). Our results (study 1) indicate that the rate of plasma tritiated water formation reflects the intracellular detritiation of tritiated glucose. Under hyperinsulinemic conditions (study 2) the net rate of muscle glycogen synthesis can be accurately estimated from the glycogen synthase activity and from the difference between total glucose uptake and glycolysis. Thus, at high physiological plasma insulin concentrations resulting in submaximal stimulation of muscle glycogen synthesis, the latter can be accurately measured in humans.

Adult↗
PubMed1993

Effects of oleate and fatty acids from omental adipocytes on insulin uptake in rat liver cells.

Hyperinsulinemia in central type (upper body) obesity has been related to reduced hepatic insulin uptake caused by fatty acids reaching the portal vein directly from the omental (visceral) fat depot. We investigated the effect of sodium oleate and fatty acid-rich buffer recovered from incubation of omental adipocytes with 10(-7) M epinephrine on specific [125I]insulin uptake (at 37 C) in freshly prepared and cultured hepatocytes and nonparenchymal liver cells isolated from 200-250 g rats. In hepatocytes, insulin uptake was studied after standard cell isolation and washing and after additional repeated 30-min washings at 37 C. In the vigorously washed hepatocytes, both fatty acid rich buffer (from 0.08-1.3 mM) and sodium oleate (from 0.0125-1.2 mM) decreased insulin uptake maximally by approximately 30% and approximately 40%, respectively (P < 0.005); a biphasic effect of fatty acids was observed, with maximal inhibition occurring at 0.08-0.1 mM. Without vigorous washing, oleate had no effect on insulin uptake in either freshly prepared or cultured hepatocytes and nonparenchymal cells. The reason for the observed inhibitory effect of fatty acids on insulin uptake in vigorously washed cells remains unknown, but the effect is unlikely to be physiologically important. Thus, our data do not support the hypothesis that the increased concentration of fatty acids in the portal vein is responsible for reduced hepatic insulin uptake and hyperinsulinemia in upper body obesity.

Adipocytes↗
PubMed1993

Glucose metabolism and leg blood flow after pancreas/kidney transplantation.

Patients with insulin-dependent diabetes mellitus (IDDM) who have undergone combined pancreas and kidney (P/K) transplantation, are hyperinsulinemic and have impaired insulin-stimulated whole body glucose uptake. We have investigated whether their reduced glucose uptake was due to insulin resistance at the tissue level or was caused by reduced muscle blood flow, previously reported to be present in patients with IDDM. Leg blood flow (LBF, determined with mercury strain-gauge plethysmography), glucose uptake (GRd, determined with 6,6 D2-glucose), and glucose oxidation (Gox, determined by indirect calorimetry) were obtained during euglycemic-hyperinsulinemic (approximately 500 pM) clamping in five P/K patients, five kidney transplant (K) patients, and six controls. Insulin-stimulated GRd was reduced in P/K patients compared to controls (23 +/- 4 vs. 44 +/- 6 mumol/kg/min, P < 0.05); Gox was comparable but glucose storage was reduced in P/K and K patients compared to controls (9 +/- 3 and 13 +/- 4 vs. 28 +/- 7 mumol/kg/min, P < 0.05). Basal LBF (3.9 +/- 0.3, 4.6 +/- 0.9, and 4.9 +/- 0.6 mL/dL leg tissue/min) and insulin-stimulated LBF (5.6 +/- 0.6, 6.1 +/- 1.1 and 6.1 +/- 0.9 mL/dL leg tissue/min) were similar in P/K, K patients, and controls. We concluded, that P/K patients had normal muscle blood flow but were insulin resistant at the tissue level, and that the insulin resistance was responsible, at least in part, for their hyperinsulinemia.

Adult↗
PubMed1993

Effects of insulin on fatty acid reesterification in healthy subjects.

The effects of insulin on triacylglycerol/fatty acid cycling (fatty acid reesterification) were studied in 12 normal subjects during euglycemic hyperinsulinemia with the use of stable isotope dilution analysis ([2H5]glycerol and [1-13C]palmitate) in combination with indirect calorimetry. During basal conditions, 5.6 +/- 0.6 mumol.kg-1 x min-1 of fatty acid were released of which approximately 3.3 mumol.kg-1 x min-1 were oxidized and approximately 2.2 mumol.kg-1 x min-1 were reesterified. A minority of the recycled fatty acid, (0.8 +/- 0.4 mumol.kg-1 x min-1) never left the intracellular space before being reesterified (intracellular triacylglycerol/fatty acid cycling), whereas the majority (1.2 +/- 0.4 mumol.kg-1 x min-1) were first released into the extracellular space and then reesterified in various organs (extracellular triacylglycerol/fatty acid cycling). In response to insulin, fatty acid release declined by 71% (from 5.6 +/- 0.6 to 1.6 +/- 0.2 mumol.kg-1 x min-1). Fatty acid oxidation (measured by indirect calorimetry) declined by 55% (from 3.3 +/- 0.3 to 1.5 +/- 0.3 mumol.kg-1 x min-1) and total triacylglycerol/fatty acid cycling was completely suppressed (from 2.2 to 0.0 mumol.kg-1 x min-1). Fatty acid release, oxidation, total and extracellular triacylglycerol/fatty acid cycling all correlated positively with plasma fatty acid concentrations. These data showed that insulin profoundly suppressed fatty acid release, oxidation as well as reesterification of those fatty acids that had entered the extracellular compartment. They suggested that physiological concentrations of insulin suppressed extracellular fatty acid reesterification primarily by inhibiting lipolysis.

Adult↗
PubMed1993

Effects of age and body fat on insulin resistance in healthy men.

OBJECTIVE: Aging is known to be associated with increasing insulin resistance and declining glucose tolerance. The cause for the insulin resistance, however, remains uncertain. In this study, we examined the hypothesis that at least part of the insulin resistance may be attributable to age-related changes in body composition and muscle blood flow rather than age itself. RESEARCH DESIGN AND METHODS: We studied 6 healthy, elderly (66.2 +/- 1.7 yr) and 6 younger, healthy men (31.8 +/- 3.0 yr) matched for height and weight by determination of their body composition (by underwater weighing), leg blood flow (by mercury strain-gauge plethysmography), rates of glucose uptake (by stable isotope dilution analysis with 6.6 D2-glucose), and carbohydrate oxidation (by indirect calorimetry) during euglycemic hyperinsulinemic clamping. RESULTS: Body fat (kg fat mass or in percentage of body weight), rates of insulin-stimulated leg blood flow, glucose uptake, oxidation, and storage were all similar in elderly and younger men. Body fat (in percentage of body weight) of both elderly and younger men correlated closely and negatively with glucose uptake (r = -0.73, P < 0.01), glucose oxidation (r = -0.67, P < 0.05), and with glucose storage (r = -0.65, P < 0.05). In contrast, age did not correlate significantly with any parameter of glucose metabolism. CONCLUSIONS: Our data suggested that insulin sensitivity in men until around 60-70 yr of age appears to be determined more by body fat than by age.

Adipose Tissue↗
PubMed1993

Effects of ethanol on carbohydrate metabolism in the elderly.

We have previously reported that in young men, ethanol caused acute insulin resistance, but compensatory insulin secretion prevented deterioration of glucose tolerance (1). In this study, we tested the hypothesis that elderly men, because of their pre-existing insulin resistance and compromised insulin secretory capacity, may experience worsening of their glucose tolerance after ethanol. Nine elderly men (65.7 +/- 0.8 yr, BMI 25.8 +/- 1.4 kg/m2) received ethanol (13 mmol/kg for 30 min i.v.) or saline followed 30 min later by i.v. glucose (2.8 mmol/kg for 5 min). To determine the mechanism of the ethanol effect, six of the men underwent euglycemic-hyperinsulinemic (approximately 350 pM) clamping with simultaneous infusion of ethanol or saline. Muscle biopsies were obtained before and 1 and 4 h after insulin infusion. In all nine men, glucose concentrations after i.v. glucose were higher after ethanol than after saline, whereas insulin was the same and glucose tolerance decreased by 23% (Kg 2.41 +/- 0.2 vs. 1.86 +/- 0.1%/min, P < 0.01). Ethanol reduced insulin-stimulated glucose uptake from 40.6 +/- 3.1 to 25.6 +/- 1.9 mumol.kg-1.min-1 (-37%, P < 0.05), glucose oxidation from 11.7 +/- 1.1 to 7.0 +/- 0.7 mumol.kg-1.min-1 (-33%, P < 0.01), and glucose storage from 28.7 +/- 2.4 to 18.6 +/- 1.7 mumol.kg-1.min-1 (-35%, P < 0.01). Ethanol increased muscle lactate concentration from 0.49 +/- 0.14 to 1.99 +/- 0.99 mumol/mg protein (P < 0.05), but had no effects on muscle concentration of free glucose, G-6-P, and citrate concentrations, nor did it affect muscle GS activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Effects of oleate and insulin on glucose uptake, oxidation, and glucose transporter proteins in rat adipocytes.

We examined effects of Na oleate on glucose uptake, glucose transporter protein concentrations, and glucose oxidation in isolated adipocytes from fed rats. Na oleate increased basel 14C-glucose uptake in a dose-dependent manner (+42% with 1.0 mM, +79% with 2.8 mM Na oleate), but had no statistically significant effect on insulin-stimulated glucose uptake. Insulin (100 nM) resulted in a redistribution of GLUT4 protein concentration from the LDM fraction (-42%) to the PM fraction (+266%) but did not affect the distribution of GLUT1. Na oleate had no effect on basal or insulin-stimulated concentrations of GLUT1 or GLUT4 proteins in the PM or LDM fractions. Na oleate (2.8 mM) had no statistically significant effect on basal glucose oxidation, but inhibited insulin-stimulated glucose oxidation by 48% (P less than 0.01). In summary, Na oleate inhibited insulin-stimulated glucose oxidation and stimulated basal glucose uptake in isolated adipocytes without affecting PM or LDM distribution of GLUT1 or GLUT4 proteins. We conclude that the stimulatory effect of Na oleate on basal glucose uptake in adipocytes may be mediated by changes in the intrinsic activity of the glucose transporters.

Adipose Tissue↗
PubMed1992

Allergen-antibody complexes in the treatment of atopic dermatitis: preliminary results of a double-blind placebo-controlled study.

Twenty-three adult patients suffering from chronic atopic dermatitis (AD) have been treated by regular injections of complexes made of D. pteronyssinus allergens and specific autologous antibodies. A double-blind placebo-controlled protocol was followed for 4 months, then the patients were treated openly to complete a full year on active therapy. Preliminary results are presented for the first 8 months. Seventy-three percent of patients improved when treated with complexes, showing a mean improvement of more than 70% after 4 months. This study suggests that injections of allergen-antibody complexes is an effective treatment of at least some forms of AD and confirms that airborne allergens are significant exacerbating factors of AD.

Adolescent↗
PubMed1991

A radioimmunoassay for human insulin receptor correlation between insulin binding and receptor mass.

We have developed a radioimmunoassay for human insulin receptor. Serum from a patient with Type B severe insulin resistance was used as anti-insulin receptor antiserum. Pure human placental insulin receptor was used as reference preparation and 125I labeled pure insulin receptor as trace. The radioimmunoassay was sensitive (limit of detection less than 17 fmol), reproducible (inter and intra-assay coefficients of variation 12.5% and 1.6% respectively) and specific (no crossreactivity with pure placental IGF-1 receptor, insulin and glucagon). The anti-insulin receptor antibody was, however, able to differentiate between insulin receptor from human placenta and from rat liver. To determine the number of insulin binding sites per receptor, we measured insulin binding (by insulin binding assay) and insulin receptor mass (by radioimmunoassay) in solubilized aliquots from 5 human placentas. The molar ratio of insulin binding to receptor mass was 0.86 +/- 0.12 when binding was determined with monoiodinated 125I-Tyr A 14-insulin. It was 1.94 +/- 0.27 when randomly iodinated 125I-insulin was used. In conclusion, using a sensitive, reproducible and specific radioimmunoassay, we have measured insulin receptor mass independent of insulin binding. Our data are most compatible with binding of one insulin molecule per human placental insulin receptor.

Autoantibodies↗
PubMed1991

Effects of fat on insulin-stimulated carbohydrate metabolism in normal men.

We have examined the onset and duration of the inhibitory effect of an intravenous infusion of lipid/heparin on total body carbohydrate and fat oxidation (by indirect calorimetry) and on glucose disappearance (with 6,6 D2-glucose and gas chromatography-mass spectrometry) in healthy men during euglycemic hyperinsulinemia. Glycogen synthase activity and concentrations of acetyl-CoA, free CoA-SH, citrate, and glucose-6-phosphate were measured in muscle biopsies obtained before and after insulin/lipid and insulin/saline infusions. Lipid increased insulin-inhibited fat oxidation (+40%) and decreased insulin-stimulated carbohydrate oxidation (-63%) within 1 h. These changes were associated with an increase (+489%) in the muscle acetyl-CoA/free CoA-SH ratio. Glucose disappearance did not decrease until 2-4 h later (-55%). This decrease was associated with a decrease in muscle glycogen synthase fractional velocity (-82%). The muscle content of citrate and glucose-6-phosphate did not change. We concluded that, during hyperinsulinemia, lipid promptly replaced carbohydrate as fuel for oxidation in muscle and hours later inhibited glucose uptake, presumably by interfering with muscle glycogen formation.

Adult↗
PubMed1991

Effects of lipid on basal carbohydrate metabolism in normal men.

We investigated the effects of infusion of a 20% triglyceride emulsion plus heparin (LH) on carbohydrate (CHO) metabolism during basal insulin and glucose turnover conditions in normal male subjects. In study 1, LH or saline was infused at 0.5 and 1.5 ml/min for 2 h each. Plasma free fatty acids rose from approximately 0.4 to 0.8 mM with the low rate and to between 1.6 and 2.1 mM with the high rate. Similar increases occurred in plasma concentrations of glycerol, acetoacetate, and beta-hydroxybutyrate. LH infusions resulted in significant increases in C-peptide concentrations but had no effects on any of the other measured parameters of CHO metabolism. In study 2, LH or saline was infused as in study 1, but the compensatory insulin release was prevented by intravenous infusion of somatostatin and replacement of basal insulin and glucagon concentrations. This resulted in significant increases in plasma glucose (from 4.5 +/- 0.2 to 7.1 +/- 0.6 mM, P less than 0.001) and hepatic glucose output (from 9.0 +/- 1.5 to 11.3 +/- 1.4 mumol.kg-1.min-1, P less than 0.05) and a decrease in glucose clearance (from 2.32 +/- 0.13 to 1.44 +/- 0.11 ml.kg-1.min-1, P less than 0.05). We conclude that lipids can have adverse effects on CHO metabolism under basal conditions and that healthy individuals can compensate for these effects with additional secretion of insulin.

3-Hydroxybutyric Acid↗
PubMed1990

Plasmacytoid monocytes in Jessner's lymphocytic infiltration of the skin.

Plasmacytoid monocytes are normal cell constituents of the human lymph node and have been found to form perivascular clusters in a case of lymphocytic infiltration of the skin. This study was undertaken to analyze the occurrence of plasmacytoid monocyte clusters in biopsy specimens from 54 patients with lymphocytic infiltration of the skin using light microscopy and immunohistochemistry. Variably sized clusters of plasmacytoid monocytes were observed in close association with dermal venules in 16 of 54 biopsy specimens and were composed of medium-sized cells, admixed with pyknotic cells and, occasionally, with tangible body macrophages. Immunohistochemistry on paraffin and on frozen sections facilitated the recognition of plasmacytoid monocytes and showed an immunophenotype similar to that observed previously on reactive lymph nodes. It is concluded that, in analogy with reactive lymph nodes, plasmacytoid monocytes represent a common constituent of the skin-associated lymphoid tissue. The striking perivascular distribution and the immunophenotypical characteristics of these monocyte-derived cells suggest they may have a role in the process of lymphocyte recruitment into the skin.

Adult↗