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Biomedical subjects

C J Bailey

Publications and source records attributed to C J Bailey.

At least 109 records · Page 6Linked to original sources
PubMed1991

Reconsideration of inhibitory effect of metformin on intestinal glucose absorption.

New evidence that metformin increases intestinal glucose metabolism has necessitated a re-examination of the effect of metformin on intestinal glucose absorption. Normal 18 h fasted mice received an intragastric bolus of metformin 2 h before preparation of everted gut sacs from the proximal, middle and distal regions of the jejunum and ileum. Net mucosal glucose transfer from the intestinal lumen into the tissue was reduced by 15 and 28% after 50 and 250 mg kg-1 metformin, respectively (ANOVA, P less than 0.05). Net glucose transfer into the serosal fluid was reduced by 12 and 70% after 50 and 250 mg kg-1 metformin respectively (ANOVA, P less than 0.05 and P less than 0.01). The inhibitory effect of metformin on both the mucosal and serosal glucose transfer mechanisms was greatest in the middle portion of the small intestine. The results suggest that metformin decreases intestinal glucose absorption in a dose-dependent manner by effects on mucosal and serosal glucose transfer.

Administration, Oral↗
PubMed1990

The reactive serine residue of epidermolytic toxin A.

Comparison of amino acid sequence data suggested that there may be a functional relationship between the staphylococcal epidermolytic toxins and V8 proteinase. The hypothesis was tested by treating epidermolytic toxin with di-isopropyl phosphorofluoridate, which bound specifically at serine-195, the homologue of the active-site serine residue of V8 proteinase.

Amino Acid Sequence↗
PubMed1990

Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice.

The effects on glucose homeostasis of eleven plants used as traditional treatments for diabetes mellitus were evaluated in normal and streptozotocin diabetic mice. Dried leaves of agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra) were studied. Each plant material was supplied in the diet (6.25% by weight) and some plants were additionally supplied as decoctions or infusions (1 g/400 ml) in place of drinking water to coincide with the traditional method of preparation. Food and fluid intake, body weight gain, plasma glucose and insulin concentrations in normal mice were not altered by 12 days of treatment with any of the plants. After administration of streptozotocin (200 mg/kg i.p.) on day 12 the development of hyperphagia, polydipsia, body weight loss, hyperglycaemia and hypoinsulinaemia were not affected by blackberry, celandine, lady's mantle or lily of the valley. Garlic and liquorice reduced the hyperphagia and polydipsia but did not significantly alter the hyperglycaemia or hypoinsulinaemia. Treatment with agrimony, alfalfa, coriander, eucalyptus and juniper reduced the level of hyperglycaemia during the development of streptozotocin diabetes. This was associated with reduced polydipsia (except coriander) and a reduced rate of body weight loss (except agrimony). Alfalfa initially countered the hypoinsulinaemic effect of streptozotocin, but the other treatments did not affect the fall in plasma insulin. The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice.

Animals↗
PubMed1990

Activity requirements of epidermolytic toxin from Staphylococcus aureus studied by an in vitro assay.

The activity of epidermolytic toxin from Staphylococcus aureus was studied in vitro using discs of neonatal mouse skin. By assessing the loss of skin integrity as a function of toxin dose and time, it was possible to put the assay on a semi-quantitative basis. Epidermolysis occurred without any change in rate from pH 3.8 to 8.7, and at an increasing rate in the temperature range of 0-37 degrees C. Activity was observed even at the lowest temperature. More than 30 inhibitors of energy metabolism, central metabolic pathways, receptor binding or proteolysis, individually failed to prevent epidermolysis and it is suggested that intoxication cannot be dependent on receptor-mediated endocytosis. Five metal-ion chelators inhibited epidermolysis, due to an effect on the tissue rather than on the toxin. Using X-ray fluorescence and atomic absorption spectroscopy, it was shown that epidermolytic toxins do not contain any essential metal ions. Some transition metals, but not Ca2+ or Mg2+, prevented the chelator-dependent inhibition of epidermolysis.

Animals↗
PubMed1990

Hypoglycaemic effect of Momordica charantia extracts.

The hypoglycaemic effect of orally administered extracts of fruits of cultivated Momordica charantia (karela) was examined in normal and streptozotocin diabetic mice. In normal mice, an aqueous extract (A) lowered the glycaemic response to both oral and intraperitoneal glucose, without altering the insulin response. This aqueous extract (A) and the residue after alkaline chloroform extraction (B) reduced the hyperglycaemia in diabetic mice at 1 hour. Material recovered by acid water wash of the chloroform extract remaining after an alkaline water wash (D) produced a more slowly generated hypoglycaemic effect. The results suggest that orally administered karela extracts lower glucose concentrations independently of intestinal glucose absorption and involve an extrapancreatic effect. Two types of hypoglycaemic substances with different time dependent effects are indicated.

Animals↗
PubMed1990

Knowledge, attitudes, technical competence, and blood glucose control of Type 1 diabetic patients during and after an education programme.

Thirty-one Type 1 diabetic patients entered a 12-month education programme in which attitudes to diabetes, knowledge of diabetes, and technical competence were assessed using questionnaires and practical tests. A closely matched group of 25 control patients continued to receive routine clinic care. Patients completing the education programme showed improved blood glucose control (HbA1 decreased from 11.8 +/- 0.4% to 10.5 +/- 0.3%, mean +/- SE, p less than 0.01), whereas blood glucose control was not altered in the control group (HbA1 11.8 +/- 0.5% before and 11.6 +/- 0.4% after 12 months). Patients completing the education programme also showed greater knowledge (p less than 0.001), more favourable attitudes (p less than 0.03), and increased competence in technical skills (p less than 0.02) compared with the control group. Six months after completing the programme blood glucose control deteriorated (HbA1 11.0 +/- 0.4%, p less than 0.05), although knowledge, attitudes, and technical competence were unchanged. This might reflect the withdrawal of extrinsic motivation and attention provided during the programme. Thus consideration should be given to development of the patient's intrinsic motivation to prolong the benefits of diabetes education programmes.

Adult↗
PubMed1990

Alloxan and ninhydrin inhibition of hexokinase from pancreatic islets and tumoural insulin-secreting cells.

Alloxan inhibited hexokinase activity in cytoplasmic fractions of transplantable radiation-induced rat islet cell tumours, ob/ob mouse pancreatic islets, rat liver and rat kidney. Half maximal inhibitory concentrations of alloxan were greater than those previously found for half maximal inhibition of pancreatic islet or liver glucokinase. D-glucose, preferentially the alpha-anomer, and D-mannose protected hexokinase activity against alloxan inhibition. 1,4-Dithiothreitol completely protected against and partially reversed the alloxan inhibition of hexokinase. The ability of various dithiols to reverse the inhibition of hexokinase by alloxan was dependent on the spacing between the SH (thiol) groups. Only dithiols with intermediate spacing between the SH groups were effective. Dithiols with two vicinal SH groups such as 1,2-dimercaptoethane and 2,3-dimercaptopropanol (BAL) and dithiols with more widely spaced SH groups such as 1,5-dimercaptopentane were ineffective. Thus a reaction of alloxan with two SH groups in the sugar binding site of the hexokinase with the formation of a disulfide bond may be involved in the reversible inhibition of the enzyme. Ninhydrin also inhibited hexokinase from all four tissues studied. The half maximal inhibitory concentrations of ninhydrin were lower than those of alloxan. Inhibition of hexokinase may be an important factor in the general cytotoxic action of ninhydrin. However, inhibition of pancreatic islet hexokinase is unlikely to be the initial event in the pancreatic B-cell toxic action of alloxan, even if inhibition of hexokinase by high concentrations of alloxan may contribute to the B-cell toxic action.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan↗
PubMed1990

Effects of gastric inhibitory polypeptide, vasoactive intestinal polypeptide and peptide histidine isoleucine on the secretion of hormones by isolated mouse pancreatic islets.

The release of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) by isolated mouse pancreatic islets was determined during 30-min incubations at 5.6 and 16.7 mmol glucose/l in the absence and presence of gastric inhibitory polypeptide (GIP), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) at concentrations of 1-1000 nmol/l. Insulin release was enhanced (greater than 50%) by GIP (100-1000 nmol/l) and VIP (1 mumol/l) at 5.6 mmol glucose/l, but not at 16.7 mmol glucose/l. Glucagon release was increased by GIP (100-1000 nmol/l), and by VIP and PHI (1-1000 nmol/l) at both glucose concentrations in a dose-related manner (maximum increases greater than tenfold). Somatostatin release was similarly increased by GIP (10-1000 nmol/l) at both glucose concentrations. Only the highest concentration (1 mumol/l) of PHI tested increased somatostatin release (twofold) at 5.6 mmol glucose/l, whereas PHI and VIP (1-1000 nmol/l) reduced (greater than 37%) somatostatin release at 16.7 mmol glucose/l. PP release was increased (49-58%) by 100-1000 nmol GIP/l, but was not significantly altered by VIP, and was reduced (39-56%) by PHI. The results indicate that GIP, VIP and PHI each stimulate glucagon release in a dose-related manner, but they exert discretely different effects on other islet hormones depending upon the dose and the prevailing glucose concentration.

Animals↗
PubMed1990

Effect of gastrin-releasing peptide on the secretion of mouse islet hormones in vitro.

Collagenase-isolated mouse islets were incubated with gastrin-releasing peptide (GRP). At 5.6 mmol glucose/l. 10 nmol GRP/l increased the release of insulin (by 50%) and glucagon (by twofold), decreased the release of pancreatic polypeptide (by 35%), but did not significantly affect the release of somatostatin. At 16.7 mmol glucose/l, 10 nmol GRP/l increased glucagon release (by fivefold) and decreased pancreatic polypeptide release (by 46%), without significantly altering insulin and somatostatin release. GRP (200 nmol/l) did not affect insulin release by perifused mouse islets at 2.8 mmol glucose/l, but increased both first and second phase insulin release after a square wave increase in the glucose concentration to 11.1 mmol/l. At 5.6 mmol glucose/l, GRP (100 pmol/1-100 nmol/l) increased (by 50-70%) insulin release by the RINm5F clonal cell line. GRP did not affect glucose oxidation or the cyclic adenosine monophosphate content of RINm5F cells. However, the intracellular free Ca2+ concentration of RINm5F cells was rapidly and transiently increased by GRP (maximum increase of 64% about 10 s after exposure to 1 mumol GRP/l). The rise of intracellular free Ca2+ was approximately halved in the absence of extracellular Ca2+. The results suggest that GRP may contribute to the normal regulation of the endocrine pancreas. The insulin-releasing effect of GRP is mediated via increased cytosolic free Ca2+, derived both from an increased net influx of extracellular Ca2+ and from mobilization of intracellular Ca2+ stores.

Animals↗
PubMed1990

Increased sensitivity to insulin-releasing and glucoregulatory effects of dynorphin A1-13 and U 50488h in ob/ob versus lean mice.

The effects of two kappa-opiate agonists, U 50488h and dynorphin A1-13, on plasma insulin and glucose concentrations in vivo and insulin release in vitro were tested in fasted genetically obese (ob/ob) and lean (+/+) mice at 12-15 wk of age. Fasting plasma insulin concentrations in ob/ob and lean mice were 1.22 +/- 0.10 and 0.23 +/- 0.05 nM, and plasma glucose levels were 6.90 +/- 0.84 and 4.70 +/- 0.29 mM, respectively. Administration of U 50488h (1 mg/kg body wt i.p.) to ob/ob mice dramatically raised plasma insulin by 670 and 790 pM at 15 and 30 min. Plasma glucose was raised from 5 min onward to a maximum increment of 4.2 mM above baseline. These effects were blocked by simultaneous administration of naloxone (10 mg/kg). A higher dose of U 50488h (10 mg/kg body wt i.p.) was required to produce significant increases in lean mouse plasma insulin (81 pM at 15 min) and glucose (0.7, 1.1, and 1.7 mM at 5, 15, and 30 min, respectively). Dynorphin (1 mg/kg body wt i.p.) raised plasma insulin in ob/ob mice by 380 and 410 pM at 15 and 30 min and raised plasma glucose by 1.6 mM at 15 min. In lean mice, the same dose of dynorphin had no effect on plasma insulin concentrations but induced a small rise in glucose. In ob/ob mice, the agonist-induced rise in glucose did not cause the insulin response, because insulin levels were not elevated by a glucose challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate.

The trace element vanadium exerts insulinlike effects in vitro and decreases hyperglycemia in insulin-deficient animals. This study examined whether vanadate can improve glucose homeostasis in genetically obese hyperglycemic insulin-resistant ob/ob mice, which present metabolic abnormalities similar to those of human non-insulin-dependent diabetes. Sodium orthovanadate (0.3 mg/ml) was administered for 7 wk in H2O. Vanadate treatment induced a fall in fed and fasted plasma glucose and insulin levels and improved tolerance to oral glucose; the stimulated glucose area was decreased by 65%, and an early peak of insulin secretion was restored. During an intravenous glucose tolerance test, the glucose disappearance rate was twofold higher in vanadate-treated mice, and the reappearance of a significant insulin response was also observed. Moreover, vanadate produced a twofold increase in hepatic glycogen content and prevented the exhaustion of pancreatic insulin stores. The hypoglycemic response to exogenous insulin was similar in control and treated mice. In vitro experiments showed that basal glucose oxidation by hemidiaphragms was 32% higher in vanadate-treated mice than in controls, although stimulation by insulin was similar in both groups. In conclusion, oral vanadate caused a marked and sustained improvement of glucose homeostasis in diabetic insulin-resistant mice by exerting an insulinlike effect on peripheral tissues and apparently preventing the exhaustion of pancreatic insulin stores.

Animals↗
PubMed1990

Adrenoceptor-mediated control of glucose homeostasis in obese hyperglycaemic (ob/ob) mice.

Adrenoceptor-mediated control of glucose homeostasis in lean (+/+) and obese hyperglycaemic (ob/ob) mice was investigated by intraperitoneal administration of alpha and beta adrenoceptor agonists and antagonists, and by chemical sympathectomy. In lean mice, beta adrenoceptor stimulation with isoprenaline (50 mumol/kg) transiently raised plasma insulin and lowered plasma glucose, while alpha adrenoceptor stimulation with phenylephrine (50 mumol/kg) transiently lowered plasma insulin and raised plasma glucose. In ob/ob mice the insulin responses to isoprenaline and phenylephrine were similar but more slowly generated and protracted. However in contrast to lean mice, isoprenaline transiently raised plasma glucose and phenylephrine lowered plasma glucose in ob/ob mice. Beta adrenoceptor antagonism with propranolol (100 mumol/kg) produced a more protracted decrease of plasma insulin in ob/ob mice than lean mice, although plasma glucose was not significantly altered in either genotype. Alpha adrenoceptor antagonism with phentolamine (100 mumol/kg) transiently increased plasma insulin and produced a protracted decrease of plasma glucose in both genotypes. Chemical sympathectomy with 6-hydroxydopamine (65 mg/kg ip) temporarily reduced food intake and plasma glucose without affecting plasma insulin in lean mice. In ob/ob mice, chemical sympathectomy produced temporary but marked reductions of food and fluid intake with concomitant reductions in plasma glucose and insulin. Plasma glucose and insulin returned almost to pretreatment values by 7 days, whereas fluid intake rose to above pretreatment amounts and food intake became maintained at the amount consumed by lean mice. Food and fluid intake returned to pretreatment amounts at 4-5 weeks. The results indicate abnormalities of adrenoceptor mechanisms in ob/ob mice which favour impaired glucose homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of diets rich in sucrose, coconut fat and safflowerseed oil on the development of the obese hyperglycaemic (ob/ob) syndrome in mice.

The effect of dietary sucrose and fat in the form of coconut fat (rich in saturated fatty acids) or safflowerseed oil (rich in polyunsaturated fatty acids) was examined on the development of obesity and impaired glucose homeostasis in ob/ob mice. Isoenergetic high sucrose or high fat diets were fed to ob/ob mice from 3-11 weeks of age. Energy intake of mice fed diets rich in fat were similar, and exceeded that attained with the sucrose diet. Body weight gain was greatest in the sucrose-fed mice and least in those fed safflowerseed oil. With the exception of insulin sensitivity which was enhanced with safflowerseed oil, plasma concentrations of glucose and gastric inhibitory polypeptide (GIP), glucose tolerance, intestinal GIP content and the GIP response to oral fat were similar. However, mice fed the high sucrose diet exhibited markedly elevated plasma insulin concentrations and an enhanced pancreatic insulin content. Since the hyperinsulinaemic action of sucrose cannot be attributed to elevated GIP or glucose concentrations, the involvement of other insulin-releasing hormones released from the intestine by sucrose is suggested. The results indicate that the relative amounts of carbohydrate and fat in the diet have an important modulating effect on the development of the ob/ob syndrome. The type of fatty acids in the diet does not appear to be a particularly important determinant for expression of the ob gene.

Animals↗
PubMed1989

Central mu, delta, and kappa opioid binding sites, and brain and pituitary beta-endorphin and met-enkephalin in genetically obese (ob/ob) and lean mice.

The equilibrium dissociation constants and maximal binding capacities of 3H-dihydromorphine (DHM), 3H-D-Ala2-D-leu3-enkephalin (DADL), and 3H-dynorphin A(1-8) for their respective mu, delta, and kappa opiate binding sites were studied in brain membrane preparations from lean and genetically obese-hyperglycaemic (Aston ob/ob) mice. The concentration of kappa binding sites was 2.7 fold higher in obese compared with lean mouse brain (231 +/- 44.6 versus 83.8 +/- 10.3 fmoles 3H-dynorphin/mg protein respectively, mean +/- SEM). The concentration of delta binding sites in obese was 1.6 fold that in lean mouse brain (94.5 +/- 8.6 versus 59.5 +/- 6.5 fmoles 3H-DADL/mg protein). In contrast, the concentration of brain mu receptors was 40% lower in obese compared with lean mice (20.8 +/- 2.19 and 34.8 +/- 3.1 fmoles 3H-DHM/mg protein respectively). Binding affinities of delta and kappa sites for their respective ligands were not significantly different in lean v. obese mice. However, for mu sites, lean mouse binding data showed two affinities, one was not significantly different from obese (0.35 nM) the second was lower (1.18 nM) for DHM. Increases of approximately 5 fold and 3 fold in the brain content of beta-endorphin and met-enkephalin respectively, and no differences in brain dynorphin levels, were demonstrated in obese mice compared with lean controls. In obese mice, pituitary beta-endorphin content was 9 fold higher, met-enkephalin 4 fold higher and dynorphin 12 fold higher than in lean mice. The striking differences in opioid binding-site characteristics and in endogenous opioid peptide levels in obese compared with lean mice may contribute to the hyperphagia and, directly or indirectly, to the development of hyperglycaemia and hyperinsulinaemia in obese mice.

Animals↗
PubMed1989

Lipoprotein subfraction composition in non-insulin-dependent diabetes treated by diet, sulphonylurea, and insulin.

Lipoprotein abnormalities may predispose to an increased risk of coronary heart disease in type II (non-insulin-dependent) diabetes mellitus. To investigate the effects of different treatment modalities, the composition and concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of patients with type II diabetes at diagnosis, treated by diet alone, treated by diet + glibenclamide (2.5 to 15 mg/d for 6 to 48 months), and treated by diet + insulin (25 to 65 U/d for 8 to 144 months). Compared with normal subjects matched for sex, age, body mass index, exercise, alcohol consumption and smoking, type II patients at diagnosis showed increased concentrations of nonesterified and esterified cholesterol, triglyceride, phospholipid, and protein in the very low density lipoprotein (VLDL) fraction. However, the only alteration in VLDL composition was a small decrease in the relative proportion of phospholipid. Apolipoprotein-B and low density lipoprotein (LDL) cholesterol concentrations were also raised in type II patients at diagnosis. Plasma concentrations of high density lipoprotein (HDL) nonesterified and esterified cholesterol, phospholipid, and apo-AI were lower in type II patients at diagnosis. This was largely accounted for by reduced concentrations of these components in the HDL2 subfraction, which retained a normal composition. Type II patients treated by diet alone and diet + glibenclamide exhibited similar abnormalities of plasma lipoprotein concentrations, which are associated with premature coronary disease, to the type II patients at diagnosis. However, in type II patients treated with insulin, plasma lipoprotein concentrations and composition were normal, except LDL cholesterol, which was lower than normal in insulin-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗