Biomedical subjects
C J Bailey
Publications and source records attributed to C J Bailey.
Stimulation of gastric inhibitory polypeptide release in ob/ob mice by oral administration of sugars and their analogues.
The effect of oral administration of sugars and their analogues (glucose, galactose, fructose, mannose, sucrose, N-acetylglucosamine, 2-deoxyglucose, 3-O-methylglucose and alpha-methyl-glucoside) on plasma gastric inhibitory polypeptide (GIP) concentration was examined in 18-h fasted ob/ob mice. Administration of sucrose (5.52 mol/kg body wt), or the monosaccharides (11.04 mol/kg body wt) glucose, galactose or fructose, elicited prompt GIP responses that peaked at 30 min. Similar effects were induced by 3-O-methylglucose or alpha-methyl-glucoside, but the stimulatory action of 2-deoxyglucose was delayed. In contrast to the other sugars, N-acetylglucosamine decreased plasma GIP concentration, while mannose exerted no effect. The results suggest that sugars using the Na+ glucose contransporter at the luminal brush border stimulate GIP release without the necessity of being metabolized or removed from the cell by the glucose transporter at the basolateral membrane. The ability of fructose to stimulate GIP release in ob/ob mice suggests that the Na+-glucose contransporter does not represent an exclusive trigger for sugar-induced GIP secretion.
Xiaoke tea, a Chinese herbal treatment for diabetes mellitus.
Xiaoke tea, a traditional Chinese treatment for diabetes mellitus, lowered blood glucose concentrations in streptozotocin diabetic mice. To investigate Xiaoke clinically, a double-blind crossover study was undertaken in 12 non-insulin-treated diabetic patients. Xiaoke tea and ordinary tea (infusion of 2.72 g, 4 times daily) were consumed in random order for 4 weeks. A standard breakfast meal was taken before and after each treatment period. Xiaoke did not significantly affect glycosylated haemoglobin, basal or post-breakfast serum glucose and insulin concentrations, intermediary metabolite concentrations, triglyceride and cholesterol. No adverse side-effects of Xiaoke were evident.
Effect of ovarian hormones, pregnancy and lactation on somatostatin and substance P in the alimentary tract of mice.
Immunoreactive somatostatin and substance P were determined in extracts of alimentary tract (stomach to colon) from the following groups of adult female mice: intact control, ovariectomized, ovariectomized and treated with oestradiol (50 micrograms/kg per day) and/or progesterone (2 mg/kg per day) for 30 days, 19-day-pregnant, and 10-day-postpartum lactating. Ovariectomy increased the somatostatin concentration of the stomach (by 52%, P less than 0.05), jejunum (by 116%, P less than 0.01) and caecum (by 114%, P less than 0.01). These effects were partially or totally prevented by the oestradiol and progesterone treatments, especially the oestradiol-progesterone combination, except for an increase (by 126%, P less than 0.01) in gastric somatostatin after treatment with oestradiol alone. Lactation also increased gastric somatostatin (by 108%, P less than 0.001), but the somatostatin concentration of other regions of the alimentary tract (jejunum to colon) was reduced (by 21-55%, P less than 0.05) in pregnant and lactating mice. The concentration of substance P was increased by ovariectomy in stomach (by 69%, P less than 0.01), duodenum (by 84%, P less than 0.05), ileum (by 163%, P less than 0.001) and caecum (by 57%, P less than 0.01). This effect was partially or totally prevented by treatment with progesterone alone and by the oestradiol-progesterone combination, but not by oestradiol alone. Pregnancy and lactation increased gastric substance P by 46% (P less than 0.01) and 61% (P less than 0.001) respectively, but substance P concentrations in other regions of the alimentary tract were not significantly altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of growth hormone-releasing hormone on the secretion of islet hormones and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats.
The effect of synthetic human growth hormone-releasing hormone(1-40) (hGHRH-40) on the function of the endocrine pancreas and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats has been examined. The addition of 1 mumol hGHRH-40/1 to incubated islets from normal lean mice increased insulin release by 90 and 37% at 5.6 and 16.7 mmol glucose/l respectively. Lower concentrations of hGHRH-40 did not affect insulin release. hGHRH-40 (1 mumol/l) increased pancreatic polypeptide release by 50% at 5.6 mmol glucose/l. A range of concentrations of hGHRH-40 (1 nmol/l-1 mumol/l) reduced glucagon release by 42-73% at 5.6 mmol glucose/l, and by 38-70% at 16.7 mmol glucose/l. Somatostatin release was increased (eightfold) by 1 mumol hGHRH-40/1 at 5.6 mmol glucose/1, but at 1 nmol hGHRH-40/1 somatostatin release was reduced (by greater than 50%). At 16.7 mmol glucose/litre 0.01-1 mumol hGHRH-40/1 increased somatostatin release (three- to fourfold), but 1 nmol hGHRH-40/1 produced a reduction of 50%. In vivo, administration of hGHRH-40 (50 micrograms/kg body weight i.p.) to fasted lean and ob/ob mice did not alter basal plasma concentrations of glucose and insulin, or the glucose and insulin responses to a concomitant i.p. glucose challenge. Intravenous injection of hGHRH-40 (20 micrograms/kg body weight) to anaesthetized rats increased plasma concentrations of insulin in the hepatic portal vein. A lower dose of hGHRH-40 (0.2 micrograms/kg) was ineffective, and neither dose of hGHRH-40 altered plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Traditional plant medicines as treatments for diabetes.
More than 400 traditional plant treatments for diabetes mellitus have been recorded, but only a small number of these have received scientific and medical evaluation to assess their efficacy. Traditional treatments have mostly disappeared in occidental societies, but some are prescribed by practitioners of alternative medicine or taken by patients as supplements to conventional therapy. However, plant remedies are the mainstay of treatment in underdeveloped regions. A hypoglycemic action from some treatments has been confirmed in animal models and non-insulin-dependent diabetic patients, and various hypoglycemic compounds have been identified. A botanical substitute for insulin seems unlikely, but traditional treatments may provide valuable clues for the development of new oral hypoglycemic agents and simple dietary adjuncts.
Epidermolytic toxin binds to components in the epidermis of a resistant species.
Ferritin-labeled epidermolytic toxin selectively bound to resin-impregnated sections of toxin-resistant rat skin. Binding was confined to the keratohyalin granules of the stratum granulosum and to the cytoplasm of cells in the stratum corneum. Single granules, and equivalent regions in composite granules, failed to bind the conjugate. Preferential binding of the ferritin-toxin probe created anastomosed arrays in the large granules. The scoring density within corneal cells varied with the position of the cell in the stratum corneum. It reached a maximum in the fourth cell from the granular-corneal junction, then decreased to a negligible value in the outermost corneal layers. Three groups of toxin-binding polypeptides were identified in epidermal extracts. These include profilaggrin, a group of three histone H1 polypeptides and histone H3. Filaggrin did not react with toxin on Western blots. The findings demonstrate that sensitivity to epidermolytic toxin is not solely dependent on the presence of target material. It is suggested that species-specific differences in the morphology of keratohyalin granules and in metabolism of profilaggrin may be important factors in intoxication.
Apolipoprotein assays: methodological considerations and studies in non-insulin-dependent diabetes treated by diet, glibenclamide and insulin.
The effect of sample pre-treatment as a source of variability of apolipoprotein (apo) AI, AII and B assays was demonstrated with lipid dissociating agents. The average mean percentage change ranged from -58 to +133% compared with untreated samples. The apolipoprotein method selected was validated by comparing their concentrations with their corresponding lipoprotein lipid or protein in normal controls and Type 2 (non-insulin-dependent) diabetic patients. The coefficient of variation was maintained below 3.5% for apo AI, AII, B and HDL2-apo AI. The apolipoprotein concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of non-obese (body-mass index less than or equal to 30) patients with Type 2 diabetes mellitus. Compared with normal subjects matched for sex, age, body-mass index, exercise, alcohol consumption and smoking. Type 2 patients at diagnosis showed reduced apo AI and HDL2-apo AI concentrations, lowered apo AI:B ratio and increased concentrations of apo B. Type 2 patients treated by diet alone (for 6-72 months) and diet plus glibenclamide (2.5-15 mg/day for 6-48 months) exhibited similar abnormalities of plasma apolipoprotein concentration to Type 2 patients at diagnosis. However, in Type 2 patients treated with insulin (25-65 U/day for 8-144 months) concentrations of apo AI and HDL2-apo AI, and the apo AI:B ratio were normal. Apo B concentrations were generally lower compared with all groups of non-insulin treated patients. These abnormalities of apolipoprotein metabolism, which are associated with premature coronary disease, are still evident in patients treated by diet and diet plus glibenclamide, but are not seen in Type 2 patients treated with insulin.
Lipoprotein subfraction composition in non-obese newly diagnosed non-insulin dependent diabetes after treatment with diet and glibenclamide.
The composition and concentrations of fasting plasma lipoproteins were determined in a prospective study of 11 +/- 2 (mean +/- 1 SD) months in 16 non-obese (body mass index less than or equal to 30) patients with Type 2 (non-insulin dependent) diabetes mellitus at diagnosis, treated by diet alone or diet plus glibenclamide (2.5-7.5 mg/day). Compared with normal subjects matched for sex, age, body mass index, exercise, alcohol consumption and smoking, Type 2 patients at diagnosis showed increased concentrations of non-esterified and esterified cholesterol, triglyceride, phospholipid and protein in the very low density lipoprotein (VLDL) fraction. The apolipoprotein (apo) B concentrations was also raised, but low density lipoprotein (LDL) cholesterol concentrations were not significantly altered in Type 2 patients at diagnosis. Plasma concentrations of high density lipoprotein (HDL) non-esterified and esterified cholesterol, HDL phospholipid and apo AI were lower in Type 2 patients at diagnosis. This was largely accounted for by a reduced number of HDL2 molecules of normal composition. After treatment of Type 2 patients with diet alone, there was a marginal increase in plasma HDL cholesterol and phospholipid, and in plasma HDL2 cholesterol, phospholipid, protein and apo AI concentrations, in association with reductions of VLDL component concentrations, body mass index and glycaemia. Type 2 patients treated with diet plus glibenclamide exhibited similar abnormalities of plasma lipoprotein concentrations before and after treatment, except for a small reduction in VLDL component concentrations and a slight increase in the apo AI:B ratio. Institution of diet alone and diet plus glibenclamide generally failed to restore VLDL, HDL and HDL2 component concentrations and the apo AI:B ratio to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice.
Twelve plants used for the traditional treatment of diabetes mellitus in northern Europe were studied using normal and streptozotocin diabetic mice to evaluate effects on glucose homeostasis. The plants were administered in the diet (6.25% by weight) and/or as decoctions or infusions in place of drinking water, to coincide with the traditional method of preparation. Treatment for 28 days with preparations of burdock (Arctium lappa), cashew (Anacardium occidentale), dandelion (Taraxacum officinale), elder (Sambucus nigra), fenugreek (Trigonella foenum-graecum), guayusa (Ilex guayusa), hop (Humulus lupulus), nettle (Urtica dioica), cultivated mushroom (Agaricus bisporus), periwinkle (Catharanthus roseus), sage (Salvia officinale), and wild carrot (Daucus carrota) did not affect the parameters of glucose homeostasis examined in normal mice (basal plasma glucose and insulin, glucose tolerance, insulin-induced hypoglycaemia and glycated haemoglobin). After administration of streptozotocin (200 mg/kg) burdock and nettle aggravated the diabetic condition, while cashew, dandelion, elder, fenugreek, hop, periwinkle, sage and wild carrot did not significantly affect the parameters of glucose homeostasis studied (basal glucose and insulin, insulin-induced hypoglycaemia, glycated haemoglobin and pancreatic insulin concentration). Guayusa and mushroom retarded the development of hyperglycaemia in streptozotocin diabetes and reduced the hyperphagia, polydipsia, body weight loss, and glycated haemoglobin. Mushroom also countered the initial reduction in plasma insulin and the reduction in pancreatic insulin concentration, and improved the hypoglycaemic effect of exogenous insulin. These studies suggest the presence of potentially useful antidiabetic agents in guayusa and mushroom.
Inhibition of hepatic gluconeogenesis by metformin. Synergism with insulin.
The antihyperglycemic agent, metformin (dimethylbiguanide), inhibits hepatic gluconeogenesis. To investigate the mechanism involved, glucose production from collagenase-isolated hepatocytes of starved rats was determined after 1 hr incubations with different substrates. In the absence of insulin, glucose production from 10(-2) M lactate-10(-3) M pyruvate, 10(-2)M M alanine, 10(-2) M glutamine and 5 x 10(-3) M glycerol was decreased (35-78%) by high concentrations (10(-2) and 10(-3) M) of metformin. Lower concentrations of metformin were not effective in the absence of insulin, but a therapeutic concentration (10(-5) M) of metformin acted synergistically with insulin (10(-8) M) to suppress gluconeogenesis from each of the substrates by an additional 10-14% compared with insulin (10(-8) M) alone. The synergistic antigluconeogenic effect of metformin (10(-5) M) with insulin (10(-8) M) was achieved without alteration of the contents of NADH and NAD+ in digitonin-separated cytosolic and mitochondrial-rich hepatocyte fractions. Mitochondrial ATP was also unaltered by the metformin (10(-5) M)-insulin (10(-8) M) combination. However, the antigluconeogenic effect of 10(-2) M metformin alone was associated with an increased (by 109%) mitochondrial NADH:NAD+ ratio. Thus reduced gluconeogenesis by high concentrations of metformin (e.g. 10(-2) M) may involve changes of redox state. However, therapeutic concentrations of metformin (e.g. 10(-5) M) potentiate the antigluconeogenic effect of insulin to a similar extent from a range of substrates, without altering energy status or redox state.
Cloning and characterization of the gene for a methanol-utilising alcohol dehydrogenase from Bacillus stearothermophilus.
The cloning and characterization of the alcohol dehydrogenase (ADH) gene (adh) from Bacillus stearothermophilus strain DSM2334, an obligate aerobe, are described. The clone directed the synthesis of ADH as judged on Western blots, activity gels and tetrazolium plates. It specified an enzyme that oxidised methanol as well as ethanol. The enzyme was found to be encoded by a single gene in B. stearothermophilus which did not cross-hybridize to adh clones from Escherichia coli, yeast or maize. The cloned gene was expressed in E. coli but activity was not detected in Bacillus subtilis, despite stable maintenance of the recombinant plasmid in this host. The gene is catabolite-repressed in DSM2334.
A new alcohol dehydrogenase, reactive towards methanol, from Bacillus stearothermophilus.
An NAD+-dependent alcohol dehydrogenase (ADH) was purified to homogeneity from an aerobic strain of Bacillus stearothermophilus, DSM 2334 (ADH 2334), and compared with the ADH from B. stearothermophilus NCA 1503 (ADH 1503). When an antibody raised against ADH 2334 was used, no cross-reactivity with ADH 1503 was observed on Western blots; by means of an enzyme-linked-immunoabsorbent-assay ('e.l.i.s.a.') procedure, it was found that ADH 1503 had less than 6% of the antigenic activity of ADH 2334. Amino acid analyses detected very small differences in composition, equivalent to about 40 sequence changes, between the two enzymes. The new enzyme has the same six-amino-acid N-terminal sequence as ADH 1503. ADH 2334, but not ADH 1503, is reactive towards methanol; both enzymes can oxidize ethanol, propan-1-ol, butan-1-ol and butan-2-ol. The new enzyme has a distinctive pH optimum at pH 5.5-6 and has significantly lower KEthanolm and kEthanolcat. values than those of ADH 1503. From steady-state kinetic parameters of the reaction with ethanol, propan-1-ol and butan-1-ol, it was shown that ADH 2334 has an ordered mechanism in both directions, with NAD+ being the compulsory first substrate in alcohol oxidation and NADH release being the rate-limiting step. ADH 1503 has an ordered addition of NAD+ and alcohol, but NADH release is not rate-limiting.
Purification of epidermolytic toxin of Staphylococcus aureus.
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Treatment--metformin.
The hyperglycaemia of NIDDM is associated with insulin resistance due, in part, to reduced insulin receptor binding and more especially postreceptor defects. Metformin is an antihyperglycaemic agent which can be used to ameliorate insulin resistance. It appears to act directly on insulin target cells to enhance insulin action. Although metformin may increase insulin-receptor binding, its main effect appears to be directed at the postreceptor level of insulin action. Accordingly the drug potentiates insulin-suppression of hepatic gluconeogenesis and increases insulin-mediated peripheral glucose uptake and metabolism. It does not stimulate insulin release, does not cause weight gain and does not cause clinical hypoglycaemia. The risk of lactate accumulation should be appreciated in patients with renal insufficiency, liver dysfunction and following acute illness with hypoxia, when therapy should be stopped. Although metformin is often bracketed with phenformin in the context of lactic acidosis, different pharmacodynamics and adherence to prescribing guidelines render such a comparison unwarranted.
A new RFLP for L1.4 (D5S4) an anonymous genomic clone localised to chromosome 5.
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Glucagon-like peptide-1 and the entero-insular axis in obese hyperglycaemic (ob/ob) mice.
The intestines of obese hyperglycaemic (ob/ob) mice contain greatly increased amounts of glucagon-like immunoreactive peptides. To investigate their role in the increased activity of the entero-insular axis of these mice, the insulin-releasing effect of glucagon-like peptide-1 (GLP-1) was examined in 24 hour fasted 12-15 weeks old ob/ob mice under conditions of basal and elevated glycaemia. Compared with glucagon (100 micrograms/kg ip), which produce an approximately 3-fold increase in basal plasma glucose and insulin concentrations, GLP-1 (100 micrograms/kg ip) produce a very small (less than 1 fold) increase in plasma insulin, with no significant change in plasma glucose. The insulin-releasing effect of glucagon, but not GLP-1 was increased by administration in combination with glucose (2 g/kg ip). The results indicate that GLP-1, which exhibits considerable sequence homology with glucagon, exerts only a weak insulin-releasing effect without a significant hyperglycaemic effect in ob/ob mice. Thus GLP-1 is unlikely to be an important endocrine component of the two over-active entero-insular axis in ob/ob mice.
RFLP for the human erb-A1 gene.
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