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Biomedical subjects

R F Weber

Publications and source records attributed to R F Weber.

At least 55 records · Page 3Linked to original sources
PubMed1991

The two different receptors for tumor necrosis factor mediate distinct cellular responses.

The individual roles of the murine type 1 and type 2 tumor necrosis factor (TNF) receptors (TNF-R1 and TNF-R2) were investigated utilizing (i) the strong species specificity of TNF-R2 for murine TNF compared to human TNF and (ii) agonistic rabbit polyclonal antibodies directed against the individual TNF receptors. Proliferation of mouse thymocytes and the murine cytotoxic T-cell line CT-6 is stimulated by murine TNF but not by human TNF. Consistent with this observation, polyclonal antibodies directed against TNF-R2 induced proliferation in both of these cell types, whereas polyclonal antibodies directed against TNF-R1 had no effect. In contrast, cytotoxicity in murine LM cells (which are sensitive to murine and human TNF) was induced by antibodies against TNF-R1 but not by antibodies against TNF-R2. Also, the steady-state level of manganous superoxide dismutase mRNA in the murine NIH 3T3 cell line was induced by murine TNF, human TNF, and anti-TNF-R1 but not by anti-TNF-R2. These results suggest that TNF-R2 initiates signals for the proliferation of thymocytes and cytotoxic T cells, whereas TNF-R1 initiates signals for cytotoxicity and the induction of the protective activity, manganous superoxide dismutase. The nonredundant signaling observed for the two TNF receptors cannot be explained simply by the differential expression of the two TNF receptors in the various cell types, because LM cells express on their surface higher levels of TNF-R2 than TNF-R1, and LM cells, NIH 3T3 cells, and thymus cells all express mRNA corresponding to both receptor types. It is therefore likely that the two receptors initiate distinct signaling pathways that result in the induction of different cellular responses.

3T3 Cells↗
PubMed1991

Prolactin stimulates rat hypothalamic corticotropin-releasing hormone and pituitary adrenocorticotropin secretion in vitro.

In rats hyperprolactinemia increases corticotropin-releasing hormone (CRH) concentration and secretion in hypophysial portal blood and the serum concentration of adrenocorticotropic hormone (ACTH). To determine whether the stimulatory effect of prolactin (PRL) on CRH and ACTH in vivo is exerted directly on the hypothalamus, hypothalamic explants and primary anterior pituitary cell cultures from adult male and female rats were used. Hypothalami explanted from male and female rats were preincubated during 90 min and treated for 30 min with rat PRL (rPRL) at concentrations of 10(-8), 10(-7), and 10(-6) M (about 200, 2,000, and 20,000 ng/ml, respectively), corticosterone at concentrations of 10(-7), 10(-6), and 10(-5) M (about 35,350 and 3,500 ng/ml, respectively), ACTH at concentrations ranging from 10(-10) to 10(-7) M (0.46, 4.6, 46, and 460 ng/ml, respectively), and graded concentrations of testosterone or estradiol. Concentrations of immunoreactive CRH (iCRH) were measured by radioimmunoassay. rPRL at 10(-6) M stimulated iCRH secretion by 360 and 400% of the basal iCRH output (about 14 pg/hypothalamus), respectively, from hypothalami explanted from male and female rats. ACTH and corticosterone did not suppress rPRL (10(-6) M) induced iCRH secretion. Corticosterone at the concentration of 10(-6) M potentiated rPRL (10(-6) M) induced iCRH secretion in hypothalami explanted from male, but not female rats. Gonadal steroids had no effect either on the basal or rPRL (10(-6) M) stimulated iCRH secretion, with the exception of estradiol which augmented the response to 10(-6) M rPRL by about fivefold, but only at the concentration of 10(-8) M (about 2.7 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1990

Evidence for the involvement of corticotropin-releasing factor in the inhibition of gonadotropin release induced by hyperprolactinemia.

The hypothesis was tested that corticotropin-releasing factor (CRF) is involved in the inhibition of gonadotropin secretion during chronic hyperprolactinemia. Two models of hyperprolactinemia were used, namely inoculation with the prolactin (PRL)-secreting tumor 7315b and implantation of isogenic pituitary glands. Gonadectomized, adrenalectomized male rats received a testosterone capsule and a corticosterone pellet and were inoculated subcutaneously with tumor 7315b. Similar rats without tumor served as controls. The rats were studied 3-4 weeks later while anesthetized with urethane. Plasma testosterone and corticosterone were similar in the two groups of rats. Compared to controls, the tumor-bearing rats had significantly higher plasma levels of PRL (100-fold increase) and adrenocorticotropin (ACTH; 3-fold increase), whereas plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) had significantly decreased to 15 and 40%, respectively. CRF release into hypophysial stalk plasma was higher in rats with tumor 7315b than in controls (298 +/- 23 vs. 197 +/- 28 pg/h), and hypothalamic CRF content had increased from 3.0 +/- 0.3 to 4.3 +/- 0.3 ng. Male rats received 3 pituitary glands under the kidney capsule. Sham-operated rats served as controls. They were studied 5-7 weeks later while anesthetized with urethane. Compared to controls, pituitary-grafted rats had larger adrenals (49 +/- 4 vs. 34 +/- 2 mg), higher plasma PRL (156 +/- 18 vs. 52 +/- 8 ng/ml), ACTH (0.46 +/- 0.05 vs. 0.22 +/- 0.02 ng/ml) and corticosterone (455 +/- 39 vs. 268 +/- 14 ng/ml), and lower plasma levels of LH (21 +/- 2 vs. 41 +/- 6 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1990

Twice daily insulin therapy in patients with type 2 diabetes and secondary failure to sulphonylureas.

In 26 type 2 diabetic patients with failure to diet and sulphonylureas (fasting blood glucose levels greater than 8.0 mmol/l) the effects of insulin therapy on blood glucose control, islet B-cell function and plasma lipids were studied. Age was 58 +/- 11 (SD) yr, median duration of diabetes 6.5, range 1-24 yr, and body mass index 24.5, range 18.9-36.3 kg/m2. Six patients were obese. Therapy comprised twice daily injections of intermediate-acting insulin with additional fast-acting insulin when necessary. After six months, insulin dose was 39 +/- 10 U in the non-obese patients. Their fasting (14.0 +/- 2.7 mmol/l) and post-prandial blood glucose (17.9 +/- 4.5 mmol/l) and glycosylated haemoglobin (HbA1, 13.0 +/- 2.0%) declined to 7.7 +/- 1.6 mmol/l, 10.6 +/- 2.6 mmol/l and 9.5 +/- 1.0%, respectively (p less than 0.001). Median body weight increased by 3.7 kg (p less than 0.001). The changes in body weight correlated well with the changes in fasting blood glucose (r = -0.75, p less than 0.01) and HbA1 (r = -0.73, p less than 0.01). Fasting plasma insulin increased (p less than 0.01), whereas fasting plasma C-peptide and C-peptide release after glucagon did not change. Free fatty acids, LDL-cholesterol, total and VLDL-triglycerides showed a significant (p less than 0.05) decrease during insulin treatment. In the six obese patients insulin dose after six months was 44 +/- 18 U. Fasting blood glucose fell from 11.3 +/- 2.2 to 8.8 +/- 2.7 mmol/l (p less than 0.01), and HbA1 decreased from 10.7 +/- 1.1% to 9.8 +/- 1.3% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1990

Clinical usefulness of serum fructosamine and HbA1 as markers for metabolic control in patients with changing insulin regimens.

The therapy of 10 patients with insulin-dependent diabetes mellitus was changed from insulin twice a day to the use of insulin pens four times a day. The possible changes in glycaemic control were monitored by day curves once a week and analysis of fructosamine and glycated haemoglobin once a fortnight. No significant changes in these parameters were seen. However, a significant decrease in the number of hypoglycaemic periods does point to an improvement of therapy. One patient having elevated values of glucose and glycated haemoglobin but "normal" concentrations of fructosamine prompted us to analyze in detail the influence of protein and albumin on fructosamine. Correction of fructosamine for low protein or albumin increases the value of this test.

Adult↗
PubMed1989

Identification of the ral and rac1 gene products, low molecular mass GTP-binding proteins from human platelets.

Identification of the GTP-binding proteins from human platelet particulate fractions was attained by their purification via successive column chromatography steps followed by amino acid sequencing. To enhance the likelihood of identifying the GTP-binding proteins, two assays were employed to monitor GTP-binding activities: (i) guanosine 5'-(3-O-[35S]thio)triphosphate (GTP gamma S)-binding followed by rapid filtration and ii) [alpha-32P]GTP-binding following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting onto nitrocellulose membranes. The latter assay permitted the isolation of a 28-kDa GTP-binding protein that bound [alpha-32P]GTP prominently but was only poorly detected with the GTP gamma S-binding assay. The amino acid sequences of three peptide fragments derived from the 28-kDa protein were identical to regions of the amino acid sequence deduced from a simian ral cDNA with the exception of one conservative substitution (Asp147----Glu). A full length human ral cDNA was isolated from a placental cDNA library, and its deduced amino acid sequence, compared with simian ral, also contained the Asp----Glu substitution along with two other substitutions and an additional three NH2-terminal amino acids. In addition to the 28-kDa protein, two distinct 25-kDa GTP-binding proteins were purified from platelets. One of these proteins has been previously characterized as G25K, an abundant low molecular mass GTP-binding protein. Partial amino acid sequence obtained from the second unidentified 25-kDa protein indicates that it is the product of the rac1 gene; a member of a newly identified gene family which encode for low molecular mass GTP-binding proteins (Didsbury, J., Weber, R.F., Bokoch, G. M., Evans, T., and Snyderman, R. (1989) J. Biol. Chem. 264, 16378-16382). These results identify two new GTP-binding proteins in human platelets, ral, the major protein that binds [alpha-32P]GTP on nitrocellulose transfers, and rac1, a substrate for botulinum C3 ADP-ribosyltransferase.

Amino Acid Sequence↗
PubMed1989

rac, a novel ras-related family of proteins that are botulinum toxin substrates.

A new family of ras-related proteins, designated rac (ras-related C3 botulinum toxin substrate) has been identified. rac1 and rac2 cDNA clones were isolated from a differentiated HL-60 library and encode proteins that are 92% homologous and share 58% and 26-30% amino acid homology with human rhos and ras, respectively. Nucleotide sequence analysis predicts both rac1 and rac2 proteins to contain 192 amino acids with molecular masses of 21,450 and 21,429 daltons, respectively. rac1 and rac2 possess four of the five conserved functional domains in ras associated with binding and hydrolysis of guanine nucleotides. They also contain the COOH-terminal consensus sequence Cys-X-X-X-COOH which localizes ras to the inner plasma membrane and the residues Gly12 and Ala59, at which sites mutations elicit transforming potential to ras. The rac transcripts, particularly rac2, display relative myeloid tissue selectivity. Both rac1 transcripts (2.4 and 1.1 kilobases (kb] increase when HL-60 cells differentiate to neutrophil-like morphology. In contrast, differentiation of U937 cells to monocyte-like morphology causes no change in the 2.4-kb mRNA and a decrease in the 1.1-kb mRNA species. rac2 mRNA (1.45 kb) increases 7-9-fold and 3-fold upon differentiation of HL-60 and U937 cells, respectively. Neither rac mRNAs are present in a Jurkat T cell line, and unlike rac1, rac2 mRNA is absent in human brain and liver tissue. Transfection experiments permitted the demonstration that rac1 and rac2 are substrates for ADP-ribosylation by the C3 component of botulinum toxin. The data suggest that racs are plasma membrane-associated GTP-binding proteins which could regulate secretory processes, particularly in myeloid cells.

Amino Acid Sequence↗
PubMed1989

A randomized crossover study of sulphonylurea and insulin treatment in patients with type 2 diabetes poorly controlled on dietary therapy.

In 13 non-obese patients with Type 2 diabetes mellitus who failed to achieve adequate blood glucose control on dietary treatment (fasting blood glucose 13.4 +/- 2.7 (+/- SD) mmol l-1, glycosylated haemoglobin 13.0 +/- 1.7%), the effects of 6 months insulin or sulphonylurea therapy on blood glucose control and lipid metabolism were compared in a randomized crossover study. Three patients, who showed a clear improvement on insulin (median glycosylated haemoglobin fell from 14.7 to 8.6%), withdrew from the study prematurely because of subjective and objective signs of hyperglycaemia after crossover from insulin to sulphonylurea. Daily dose after 6 months was 2000 mg tolbutamide (n = 3), 18 +/- 1 mg glibenclamide (n = 7), or 34 +/- 3 U insulin. On insulin, fasting (8.0 +/- 1.9 mmol l-1) and postprandial blood glucose (10.4 +/- 2.7 mmol l-1), and glycosylated haemoglobin (9.5 +/- 1.1%) were lower than on sulphonylurea (11.0 +/- 3.4 mmol l-1, 14.4 +/- 4.8 mmol l-1 and 11.0 +/- 2.5%, respectively, p less than 0.05 in each case). Median increase in body weight was greater on insulin (4.2 vs 1.1 kg, p less than 0.05). Six patients experienced improved well-being on insulin compared with sulphonylurea. Median plasma non-esterified fatty acids decreased from 825 mumol l-1 to 476 mumol l-1 (sulphonylurea) and 642 mumol l-1 (insulin, both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1989

Effects of the new prolactin-producing tumour 7315b on gonadotrophin secretion in adult male and female rats.

The effects of the transplantable purely prolactin-secreting tumour 7315b on serum gonadotrophins were studied in adult rats. Possible contributions of the adrenals to the tumour-induced inhibition of serum LH and FSH were evaluated. The suppressive actions of tumour 7315b on serum gonadotrophins in gonadectomized plus adrenalectomized male and female rats were compared. Within 4 weeks after inoculation of tumour 7315b in intact male rats very high levels of prolactin and decreased serum levels of gonadotrophins and testosterone were recorded. At autopsy reduced weights of testes and accessory sex organs and slightly increased adrenal weights were found. In addition, in animals treated with a small testosterone-filled capsule after castration, tumour 7315b reduced serum concentrations of LH and FSH. Adrenalectomy did not prevent this suppressive action of the tumour on the post-castration rise of serum gonadotrophins. Suppression of serum gonadotrophins during hyperprolactinaemia was greater in gonadectomized plus adrenalectomized female rats than in male rats, indicating that the degree of the tumour-induced suppression of LH and FSH after castration is determined to a large extent by the sex of the animal. The purely prolactin-secreting tumour 7315b has therefore been shown to be a suitable model for studying the effects of severe hyperprolactinaemia on the pituitary-gonadal axis in rats.

Adrenalectomy↗
PubMed1989

Limitations of diet therapy in patients with non-insulin-dependent diabetes mellitus.

UNLABELLED: Sixty-one patients with non-insulin-dependent diabetes mellitus and fasting blood glucose of 12.0 +/- 0.6 mmol/l were studied before and after dietary treatment in an outpatient setting. At the start of the study 33 patients were obese (body mass index greater than 27.0 kg/m2). Twenty patients were newly diagnosed, median known duration of diabetes in the others was 5 years. Beta-cell function was measured by the release of C-peptide after i.v. injection of 1 mg glucagon (area under the curve of C-peptide = AUC-cp), as well as calculated according to the formulae of Matthews. Insulin action was estimated by measurement of fasting blood glucose, insulin and free fatty acids (FFA) concentrations. Non-obese patients showed more severe beta-cell deficiency than the obese ones (AUC-cp 2586 +/- 158 vs. 3294 +/- 277 pmol/l per 15 min), and did not improve in metabolic control during treatment. In the obese patients three response patterns to treatment were observed: weight loss and improvement in metabolic control accompanied primarily with increased beta-cell function or increased insulin action, or worsening of metabolic control. Those with less impaired beta-cell function and shorter known duration of diabetes showed the most favourable response. IN CONCLUSION: non-obese type 2 diabetes patients with fasting glucose levels above 10 mmol/l do not improve on dietary treatment alone; in obese type 2 diabetics weight reduction is essential and results in metabolic improvement, irrespective of the preceding fasting blood glucose concentrations. Improved beta-cell function as well as increased insulin action are responsible for this improvement.

Adolescent↗
PubMed1988

The cpx proteins of Escherichia coli K12. Structure of the cpxA polypeptide as an inner membrane component.

Gene cpxA of Escherichia coli K12 encodes the 52,000 Mr CpxA polypeptide. The complete cpxA nucleotide sequence, reported here, predicted that CpxA contains two extended, hydrophobic segments in its amino-terminal half and could therefore be a membrane protein. Using a lac-cpxA operon fusion plasmid to overproduce CpxA and an immunochemical assay to detect the polypeptide, we show that CpxA fractionated with the bacterial inner membrane during differential and isopycnic sedimentation. Moreover, the protein could be solubilized by extraction of crude membranes with non-ionic detergents but not with KCl or NaOH, indicating that Cpx is an intrinsic membrane component. Analysis of TnphoA insertions in cpxA indicated that the region between the hydrophobic segments of CpxA is periplasmic, whereas the region carboxy-terminal to the second such segment is cytoplasmic. Based on these structural data, we propose that CpxA functions as a trans-membrane sensory protein. The DNA sequence data also indicate that cpxA is the 3' gene of an operon.

Base Sequence↗
PubMed1988

Deterioration of male sexual behavior in rats by the new prolactin-secreting tumor 7315b.

The effects of hyperprolactinemia on male copulatory behavior in adult male and female rats were studied. Hyperprolactinemia was induced by the transplantable purely prolactin-secreting tumor 7315b. Male rats were castrated and received testosterone-filled capsules of different sizes which induced normal and subnormal testosterone levels. After sexual training the rats of the experimental groups were inoculated with tumor 7315b. Three weeks after tumor-inoculation high prolactin levels (2000-30000 ng/ml) were found. During this hyperprolactinemia ejaculation latency increased significantly, while the mount frequency and intromission frequency remained unchanged. Only 9 out of 22 rats ejaculated 19 days after inoculation. Moreover, it appeared that the inhibitory effect of the tumor was as strong in the presence of normal (2.33 +/- 0.07 ng/ml) as in the presence of low (0.35 +/- 0.01 ng/ml) testosterone levels. The inhibitory effect of tumor 7315b on copulatory behavior was not influenced by adrenalectomy. In gonadectomized female rats bearing testosterone-filled capsules tumor 7315b induced prolactin levels of about 2000 ng/ml and an almost complete cessation of mounts and intromission patterns 4 weeks after tumor-inoculation. It was concluded that tumor 7315b causes a strong inhibitory effect on male copulatory behavior in male and female rats and that this effect is not influenced by the presence of normal or low testosterone levels or removal of the adrenals, suggesting a direct effect of prolactin on brain functions.

Animals↗
PubMed1988

Effects of corticosterone on the negative feedback action of testosterone, 5 alpha-dihydrotestosterone and estradiol in the adult male rat.

Corticosterone acetate (10 mg/day) was administered to gonadectomized and adrenalectomized male rats bearing 5, 10 or 15 mm long testosterone filled silicone elastomer capsules. It was found that the serum testosterone levels induced by these capsules were not influenced by corticosterone treatment and that the weights of the prostates in the corticosterone treated rats were not different from their controls. In contrast, corticosterone acetate increased markedly the LH and FSH inhibitory effects of testosterone. Since several brain structures are able to convert testosterone into 17-beta-hydroxy-5-alpha-androstan-3-one (5-alpha-dihydrotestosterone) and/or estradiol, and these metabolites are probably involved in mechanisms controlling gonadotropin secretion, we studied also the effects of corticosterone on the feedback action of dihydrotestosterone and estradiol. 5 alpha-Dihydrotestosterone was administered by 5, 10 or 20 mm long elastomere capsules whereas estradiol was given by daily s.c. injections of 0.125, 0.25 or 0.50 micrograms estradiol benzoate. In the presence of corticosterone acetate the gonadotropin inhibitory action of testosterone, 5 alpha-dihydrotestosterone and estradiol increased more than 2 times.

Adrenalectomy↗
PubMed1987

In vivo release of dopamine, luteinizing hormone-releasing hormone and thyrotropin-releasing hormone in male rats bearing a prolactin-secreting tumor.

The present study was concerned with the effects of a transplantable prolactin-secreting pituitary tumor (7315b) on the hypothalamic release of dopamine, luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) in gonadectomized, adrenalectomized male rats bearing subcutaneously a testosterone capsule and a corticosterone pellet. Similar male rats not inoculated with tumor served as controls. The rats were studied 3-4 weeks after tumor inoculation, while they were anesthetized with urethane. Compared to the controls, prolactin levels in the tumor-bearing rats had increased 70-fold, whereas the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) decreased to 20 and 27%, respectively. In tumor-bearing rats, the secretion of dopamine into hypophysial stalk plasma increased from 2.3 to 4.9 ng/h (p less than 0.025), whereas that of LHRH decreased from 127 to 52 ph/h (p less than 0.005). Since the use of urethane anesthesia may change quantitatively and qualitatively the effects of hyperprolactinemia, it was decided to study these effects on the in vivo release of LHRH, dopamine and TRH in conscious rats by a push-pull perfusion of the median eminence-arcuate nucleus area. Using this technique, it was found that in tumor-bearing rats the secretion of LHRH decreased from 20.0 to 9.8 pg/15 min (p less than 0.005), whereas that of dopamine increased from 118 to 246 pg/15 min (p less than 0.025). The secretion of TRH was not altered by hyperprolactinemia (4.1 vs. 4.4 pg/15 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1987

The contribution of corticosterone and testosterone to the suppression of serum LH in hyperprolactinaemic adult male rats with pituitary transplants.

The effects of hyperprolactinaemia on serum levels of LH were investigated in adult male rats of the R X U strain. Hyperprolactinaemia was induced by three pituitary grafts under the kidney capsule, transplanted on day 0 of each experiment. Special attention was paid to the contribution of prolactin-stimulated testes, adrenals and corticosterone. In experiment 1, hyperprolactinaemia significantly reduced the serum concentrations of LH in intact rats. In spite of a significant increase in the serum levels of corticosterone, serum testosterone was not significantly affected by hyperprolactinaemia. The weights of both the adrenals and accessory sex glands were significantly increased at autopsy. In experiment 2, treatment with 10 mg corticosterone s.c. daily from day 14 to day 28 after pituitary grafting significantly reduced serum levels of both LH and testosterone. The suppression of testosterone in the hyperprolactinaemic corticosterone-treated animals was significantly less than in the corticosterone-treated control animals. The weights of the accessory sex glands were significantly increased in the hyperprolactinaemic animals. In experiment 3, rats were adrenalectomized and half of them were substituted with corticosterone. Serum testosterone levels significantly increased in both hyperprolactinaemic adrenalectomized rats and in adrenalectomized corticosterone-treated animals without any significant effect on serum LH. Again the weights of the accessory sex glands were significantly increased in the hyperprolactinaemic animals. In experiment 4, rats were adrenalectomized, gonadectomized and corticosterone treated on day 0 and then implanted with a 2, 1.5 or 1 cm silicone elastomer capsule containing testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1986

Beta-blockade and carbohydrate metabolism: theoretical aspects and clinical implications.

The adrenergic control of carbohydrate metabolism is expressed at two levels: regulation of substrate flow, and interference with the secretion of hormones. Normally, this adrenergic regulatory system only plays a minor role. However, it is of great importance as an acute adaptation of the body to fight and flight. Under these circumstances, fuel fluxes increase almost instantaneously. Glycogenolysis and gluconeogenesis are responsible for increased hepatic glucose output. Increased fatty acid flux is brought about by stimulated adipose tissue lipolysis, which probably, as a secondary phenomenon, causes decreased peripheral glucose utilisation by the skeletal muscle mass. Cerebral glucose uptake accounts for half the body's basal glucose production. Since this glucose uptake is concentration-dependent only, hypoglycaemia rapidly leads to cerebral dysfunction. To guarantee cerebral glucose uptake, the body has a dual defense mechanism against hypoglycaemia: hormonal and metabolic counteraction. The first consists of the secretion of glucagon and (nor)epinephrine, the latter of hepatic autoregulation and alternative fuels for noncerebral tissues. In clinical practice, the inappropriate insulin-excess state forms the major cause of hypoglycaemia. There is, however, a second reason why patients with diabetes mellitus are at risk. Diabetes by itself leads to impaired glucagon secretion and, when autonomic neuropathy exists, to diminished (nor)epinephrine secretion. Thus, interference with the latter, such as administration of beta-blocking agents, further impairs hypoglycaemic counterregulation. In fact, numerous studies document delayed recovery from experimentally induced hypoglycaemia in diabetic patients receiving beta-blocking agents. However, using beta 1-selective blocking agents, mean recovery from hypoglycaemia in groups of diabetic patients demonstrates minor delay only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗