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Biomedical subjects

R Prager

Publications and source records attributed to R Prager.

At least 127 records · Page 7Linked to original sources
PubMed1986

Effect of metformin on peripheral insulin sensitivity in non insulin dependent diabetes mellitus.

To test whether metformin treatment might improve peripheral insulin sensitivity in non insulin dependent diabetes, we measured peripheral glucose uptake in 12 non insulin dependent diabetics before (A) and after 4 weeks (B) of metformin therapy (2 X 850 mg/day) by the hyperinsulinemic clamp technique (80 mU/m2/min). In addition, insulin binding to monocytes was compared between A and B. Diabetic control, evaluated by measurement of fasting blood glucose and glycosylated hemoglobin, was significantly improved by metformin treatment (P less than 0.01). Insulin binding to monocytes was not significantly influenced by metformin (A-4.53% vs. B-5.12%, n.s. at insulin tracer concentration). Peripheral glucose utilisation improved slightly, but significantly after 4 weeks of metformin therapy (A: 4.4 +/- 0.6 mg/kg/min, B: 5.4 +/- 0.8 mg/kg/min, p less than 0.01). Improvement in peripheral glucose utilisation correlated significantly with improved metabolic control, estimated by fasting blood glucose measurements (p less than 0.01).

Adult↗
PubMed1985

Severe hyperprolactinaemia is associated with decreased insulin binding in vitro and insulin resistance in vivo.

We studied insulin receptor binding and carbohydrate metabolism in 10 patients with severe hyperprolactinaemia and compared the findings with those obtained in 20 healthy control subjects. Insulin binding to monocytes and erythrocytes was significantly decreased in the patients with an excess of prolactin. Scatchard analysis of binding data indicated that a decrease in the number of receptors rather than in receptor affinity seems to be the prevailing cause of lowered binding in hyperprolactinaemic patients. Furthermore, patients with severe hyperprolactinaemia demonstrated significantly elevated blood glucose levels following oral or intravenous glucose load despite having significantly increased insulin levels after glucose administration. The infusion of insulin induced a delayed hypoglycaemic effect and a decreased inhibition of endogenous insulin secretion, as indicated by the suppression of C-peptide in the hyperprolactinaemic patients. The present data indicate that severe hyperprolactinaemia is associated with an insulin-resistant state, which seems to be caused, at least in part, by a down-regulation of insulin receptors.

Adult↗
PubMed1985

Glucose metabolism and insulin sensitivity in patients on chronic hemodialysis.

In order to evaluate the potential role of parathyroid hormone on glucose metabolism in patients on chronic hemodialysis hyperglycemic clamp studies were performed in 7 parathyroidectomized and 11 nonparathyroidectomized patients on chronic hemodialysis and in healthy controls. There were no significant differences in the peripheral glucose uptake of the 3 groups. The beta cell response to hyperglycemia during the early phase as well as during the steady state was almost identical in controls and in nonparathyroidectomized uremics, whereas in the parathyroidectomized group a markedly enhanced insulin secretion was found. Calculated tissue sensitivity to insulin therefore was equal in controls and in nonparathyroidectomized uremics, whereas patients after parathyroidectomy had peripheral insulin resistance. Our results demonstrate that patients on chronic hemodialysis apparently have normal peripheral glucose uptake. The subgroup of patients who have undergone parathyroidectomy, however, show an enhanced insulin response to hyperglycemia suggesting peripheral insulin resistance. We conclude that longstanding and severe secondary hyperparathyroidism--the usual cause for parathyroidectomy in these patients--results in irreversible insulin resistance with a compensatory increase of insulin secretion.

Adult↗
PubMed1984

Decreased insulin receptor binding in hyperthyroidism.

The binding of 125I-insulin to insulin receptors on circulating mononuclear leukocytes was studied in ten patients with hyperthyroidism and 20 euthyroid normal volunteers. The hyperthyroid patients demonstrated significantly elevated glucose levels following an oral glucose load, despite normal insulin secretion. The infusion of insulin resulted in a delayed hypoglycaemic effect in the hyperthyroid patients; however, the inhibition of the endogenous insulin secretion as indicated by suppression of C-peptide levels was not different from euthyroid control subjects. Insulin binding to monocytes was significantly decreased in the hyperthyroid patients. Scatchard analysis of binding data indicates that a decrease of receptor number rather than receptor affinity seems to be the cause of the lowered insulin binding in hyperthyroid patients with diffuse toxic goitre. The findings of decreased insulin receptor number, mild degree of glucose intolerance despite normal insulin secretion and the delayed hypoglycaemic effect following insulin infusion suggest that peripheral insulin resistance could be involved in the highly complex pathophysiology of glucose intolerance in hyperthyroidism.

Adult↗
PubMed1984

[Continuous arteriovenous hemofiltration in the therapy of acute renal insufficiency].

30 patients with acute renal failure were treated in an intensive care unit by continuous arterio-venous haemofiltration (CAVH). This procedure has less side effects as compared with intermittent haemodialysis, peritoneal dialysis and haemofiltration (hypotension, bio-incompatibility and lack of biochemical steady state) and CAVH is clearly superior with regard to fluid removal. In removing the uraemic toxins CAVH is more effective than peritoneal dialysis and, in most instances, satisfactory as sole renal replacement therapy in acute renal failure.

Acute Kidney Injury↗
PubMed1984

Primary hyperparathyroidism is associated with decreased insulin receptor binding and glucose intolerance.

We studied insulin receptor-binding and carbohydrate and metabolism in 15 patients with symptomatic primary hyperparathyroidism in comparison with 20 healthy controls. Insulin binding to monocytes and erythrocytes was measured by radioreceptor-ligand-assay. Furthermore, patients and controls were characterized by testing oral (100 g glucose load) glucose tolerance as well as insulin tolerance (0.1U insulin/kg body weight). Compared with controls, patients with primary hyperparathyroidism exhibited marked hyperinsulinemia (P less than 0.01) and significantly higher glucose levels (P less than 0.01) after an oral glucose load. The glucose lowering effect of intravenous insulin was significantly diminished in primary hyperparathyroidism compared with controls (P less than 0.01). Receptor studies revealed a significantly lower (P less than 0.01) insulin binding to monocytes and to erythrocytes in patients with primary hyperparathyroidism compared with controls. The present data indicate an insulin-resistant state in primary hyperparathyroidism, which is caused at least in part, by a downregulation of insulin receptors.

Adult↗
PubMed1984

Plasmid-borne streptothricin resistance in gram-negative bacteria.

Plasmids, which code for a new type of drug resistance due to the acetylation of streptothricin and belonging to various incompatibility groups (I1, I2, W3, FII, S, X, and N) were identified in gram-negative bacteria. The gene for the acetyltransferase is closely linked to a gene for the streptomycin/spectinomycin adenylyltransferase AAD-3" on a novel type of a transposon, designated Tn1825. This is related to Tn7.

Acetyltransferases↗
PubMed1984

[Insulin receptor and postreceptor disorders: significance for the development and therapy of carbohydrate metabolic disorders].

The last decade has witnessed an explosion in our knowledge of the role of hormonal and neurotransmitter receptors in biological processes. The understanding gained of the interaction of insulin with its receptor has led to the recognition of receptor and postreceptor defects in various insulin resistant states. The purpose of this review is to summarize the actual state of knowledge concerning physiology and pathophysiology of insulin receptors and to relate these data to the role of insulin resistance in various pathological and non-physiological states. In addition, postreceptor abnormalities in a variety of disorders are reviewed. A number of possibilities for therapeutic intervention in insulin resistant states according to the specific underlying mechanism are described.

Autoantibodies↗
PubMed1984

[Genetic causes of possible pathogenicity factors of urinary tract strains (E. coli)].

E. coli strains isolated from urinary specimens of patients suffering from pyelonephritis can be defined as uropathogenic by the following entities: production of hemolysins, adhesins and hydroxamates, serum resistance, capsule formation and specific O: H antigenes. The presence of these properties do not coincide with the carriage of specific plasmids encoding these functions. Moreover, using the plasmid pattern analysis identical uropathogenic clones distributed among the patients investigated could not be detected. These data point to the facts that in spite of specific marker combinations which give rise to uropathogenicity, a full range of different biological qualified strains occur. The clinical significance of these strains remain to be elucidated.

Adult↗
PubMed1983

A mechanism for the transfer of the carboxyl-group from 1'-N-carboxybiotin to acceptor substrates by biotin-containing enzymes.

Previous proposals for the mechanism by which biotin-dependent enzymes catalyse the transfer of the carboxyl group from 1'-N-carboxybiotin to acceptor molecules do not appear to be consistent with all of the experimental observations now available. We propose a multi-step mechanism in which (a) substrate and then carboxybiotin bind at the second partial reaction site, (b) a base positioned adjacent to the 3'-N of the carboxybiotin abstracts a proton from the 3'-N and (c) the resulting enolate ion and the acceptor substrate undergo a concerted reaction resulting in carboxyl-group transfer.

Binding Sites↗
PubMed1983

Insulin binding of human and porcine monocomponent insulin to monocytes in type 1 (insulin-dependent) diabetic patients and control subjects.

In the present study insulin binding properties of human semi-synthetic and porcine insulin were compared in Type 1 (insulin-dependent) diabetic patients treated from the onset of their disease either with human semi-synthetic insulin (n = 12) or porcine insulin (n = 12) and control subjects (n = 12). In all three groups, insulin binding to circulating monocytes revealed no difference between human semi-synthetic and porcine insulin (specific insulin binding at tracer concentration: 5.7 +/- 0.5% versus 5.4 +/- 0.5% in control subjects, 5.5 +/- 0.4% versus 5.4 +/- 0.4% in Type 1 diabetic patients on porcine insulin, 5.3 +/- 0.4% versus 5.6 +/- 0.4% in Type 1 diabetic patients on human insulin). Treatment with human or porcine insulin did not have any significant influence on receptor binding properties of the two diabetic groups investigated. Absolute receptor number and affinity of both diabetic groups were within the range of healthy control subjects irrespective of treatment with human or porcine insulin.

Adult↗
PubMed1983

Apolipoproteins (A-I, A-II, B), Lp(a) lipoprotein and lecithin: cholesterol acyltransferase activity in diabetes mellitus.

Concentrations of HDL cholesterol, apolipoprotein (apo) A-I and apo A-II were found to be significantly decreased in patients with insulin-dependent diabetes (IDD) and non-insulin-dependent diabetes (NIDD) compared with carefully selected controls matched for sex, age and body weight. LDL cholesterol and apo B levels did not differ significantly between diabetics and controls. Concentrations of lipoprotein Lp(a), an independent risk factor for coronary artery disease in non-diabetics, were above 20 mg/dl in only 14% of diabetics and in 5% of controls. LCAT activity was normal in diabetics, irrespective of type of diabetes, sex and age of patients. No correlation between HbA1 and either HDL cholesterol or A-I and A-II was found in IDD and NIDD. A positive correlation between HbA1 and either triglyceride or VLDL triglyceride was noted in IDD and NIDD. There was also a positive correlation between insulin dosage in IDD and HDL cholesterol, apolipoprotein A-I and A-II.

Adolescent↗
PubMed1983

Peripheral insulin resistance in primary hyperparathyroidism.

Carbohydrate metabolism was investigated in 9 patients with symptomatic primary hyperparathyroidism. Before and after parathyroidectomy intravenous and oral glucose tolerance test, tolbutamide test, arginine infusion test and insulin tolerance test were performed. During intravenous and oral glucose tolerance tests, patients with primary hyperparathyroidism exhibited hyperinsulinemia and impaired glucose tolerance without normalization after surgery. Tolbutamide-induced induced insulin release did not differ pre- or postoperatively. After restoration of normocalcemia and normocalcemia and normophosphatemia we found significantly lower glucose and insulin levels following arginine infusion and a significantly increased hypoglycemic response to parenterally administered insulin, probably indicating partial improvement of glucose tolerance after surgery. Our findings suggest that biochemical abnormalities associated with primary hyperparathyroidism, like hypercalcemia, hypophosphatemia, and elevated parathyroid hormone levels may cause and sustain a form of endogenous insulin resistance, which consequently leads to hyperinsulinemia and to impaired glucose tolerance. Since hyperinsulinemia as well as impaired glucose tolerance seem to be only slowly and partially reversible in symptomatic primary hyperparathyroidism, these data could be considered as an additional argument for early surgical intervention in this disorder.

Adult↗
PubMed1983

Spontaneous arteriovenous plasma separation.

Plasmapheresis (PP) therapy was carried out by spontaneous arteriovenous membrane plasma separation. By cannulating the femoral artery and vein by Seldinger technique, this method could be performed by natural arteriovenous pressure gradient without blood pumps or special monitoring. Eight patients experienced 44 PP therapies without complication in the ICU. Spontaneous arteriovenous membrane plasma separation can suitably be combined with continuous arteriovenous hemofiltration.

Adult↗
PubMed1983

Growth hormone, prolactin and insulin following arginine infusion in primary hyperparathyroidism before and after parathyroidectomy.

The secretion of growth hormone, prolactin and insulin following arginine infusion was studied in 9 patients with primary hyperparathyroidism before and after parathyroidectomy. Growth hormone, insulin and glucose levels after arginine administration were significantly higher before parathyroidectomy compared with the corresponding data obtained in the post-operative state, whereas plasma prolactin concentrations did not differ before and after operation.

Adult↗
PubMed1983

Insulin receptor binding to monocytes, insulin secretion, and glucose tolerance following metformin treatment. Results of a double-blind cross-over study in type II diabetics.

We studied the effect of metformin therapy (1700 mg daily) on glucose tolerance, insulin secretion, and insulin binding to monocytes in 10 non-insulin-dependent diabetics (mean duration of disease 2.6 yr) who were treated for 4 wk with either metformin or placebo in a double-blind cross-over study. Metformin induced a significant decrease of glucose levels during an oral glucose load compared with placebo treatment (P less than 0.001). All patients studied showed normal or elevated basal insulin and C-peptide levels; their responses to an oral glucose load, however, were relatively hypoinsulinemic without any significant difference between metformin and placebo. Insulin binding to monocytes was nearly identical at all insulin concentrations tested in the placebo or metformin therapy phase. These data indicate that the glucose-lowering potency of metformin in non-insulin-dependent diabetics cannot be associated with changes in receptor number or affinity. It is suggested that metformin might have a positive influence on postreceptor defects in non-insulin-dependent diabetics.

Adult↗