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Biomedical subjects

C J Bailey

Publications and source records attributed to C J Bailey.

At least 199 records · Page 11Linked to original sources

Regulation of plasma immunoreactive glucagon in obese hyperglycaemic (ob/ob) mice.

This study examines the role of glucagon in the pathogenesis of the obese hyperglycaemic (ob/ob) syndrome in mice. Plasma C-terminal immunoreactive glucagon concentrations were measured in fed and fasted ob/ob mice at different ages between 5-40 weeks, and in 20-week-old mice after the administration of established stimulators and inhibitors of glucagon secretion. Plasma glucagon concentrations were inappropriately raised irrespective of age, nutritional status and the accompanying prominent changes in plasma glucose and insulin concentrations. Glucose suppressed plasma glucagon in the fed but not the fasted state, suggesting a dependence on the marked hyperinsulinaemia associated with feeding. Administration of 0.25 units insulin/kg to fasted mice failed to affect plasma glucagon and glucose concentrations. Increasing the dose to 100 units/kg restored the normal suppressive actions of insulin. Fasted mice showed an exaggerated glucagon response to arginine but not to the parasympathomimetic agent pilocarpine. Fed mice displayed normal plasma glucagon responses to the sympathomimetic agents noradrenaline and adrenaline. Administration of insulin antiserum or 2-deoxy-D-glucose raised plasma glucagon concentrations of fed mice. Contrary to the lack of suppression by glucose in the fasted state, heparin-induced increase in free fatty acids reduced plasma glucagon concentrations. This study demonstrates inappropriate hyperglucagonaemia and defective A-cell function in ob/ob mice. The extent of the abnormality is exacerbated by fasting and appears to result from insensitivity of the A-cell to the normal suppressive action of insulin.

Animals↗

High density lipoprotein cholesterol and apolipoprotein a-1 concentrations in non-insulin dependent diabetics treated by diet and chlorpropamide.

Fasting serum concentrations of high density lipoprotein cholesterol (HDLC) and apolipoprotein A-I (apo A-I) were determined in non-insulin dependent diabetes at diagnosis, diabetics treated by diet alone, diabetics treated by diet plus chlorpropamide, and normal controls matched for sex, age and body weight. Serum concentrations of HDLC and apo A-I were decreased in all groups of diabetics. There were no significant differences in HDLC and apo A-I concentrations between the diabetics at diagnosis and those treated by diet alone or diet plus chlorpropamide. Neither HDLC nor apo A-I concentrations were correlated with glucose concentrations. The results indicate that serum concentrations of HDLC and apo A-I are reduced in non-insulin dependent diabetics at diagnosis, and are not significantly affected by chronic diet and chlorpropamide therapy.

Apolipoprotein A-I↗

Influence of genetic background and age on the expression of the obese hyperglycaemic syndrome in Aston ob/ob mice.

Expression of the obese hyperglycaemic (bo/ob) syndrome in mice is modified by the background genome. The Aston colony carries the ob gene on a mixed background which produces a unique combination of different features shown by ob/ob mice on other backgrounds. The maximum body weight of Aston ob/ob mice exceeded that of other colonies, possibly reflecting a trait for higher growth rate in the background genome. The hyperphagia, marked hyperinsulinaemia and moderate hyperglycaemia observed during the development of the syndrome receded in old mice. Plasma glucagon concentrations in the fed state were similar to +/+ mice and did nor Vary throughout life. Hyperplasia of the B-cells increased inordinately during the development of the syndrome, but declined in older mice coincident with progressive intercellular vacuolation and the appearance of acinar-like cells within the islets. A-cell hyperplasia was greater in young mice, and A-cells became relocated throughout the islets of older mice. The distinct pattern of age-related changes in ob/ob mice indicates that experiments using this gene type should define clearly their age as well as genetic background.

Aging↗

Dark-adapted sensitivity, rhodopsin content, and background adaptation in pcd/pcd mice.

Adaptation to steady background lights has been investigated in pcd/pcd mice, a mutant strain with retinal degeneration. The hyperbolic stimulus/response functions of the scotopic b-wave of the electroretinogram show progressive changes. For the dark-adapted eyes the decrease in log sensitivity between ages 1 and 12 months is related linearly to the decreasing rhodopsin content. The observed decline in amplitude of maximum responses from dark-adapted eyes begins only after age 5 months and is accompanied by gradual prolongation of the time to the peak of half-maximum b-wave responses. At all ages, the sensitivity of response is changed little by increments of steady red background lights; the greatest slope of log sensitivity vs. log background plots is about +0.2. (In normal mice the slope is about +0.9.) The pcd/pcd b-wave results do not fit the normal empirical relation that is thought to reflect neural processing in the distal retina. Thus the present results suggest that neural processing is abnormal in pcd/pcd retinas.

Adaptation, Physiological↗

Improvement in glucose tolerance due to Momordica charantia (karela).

The effect of karela (Momordica charantia), a fruit indigenous to South America and Asia, on glucose and insulin concentrations was studied in nine non-insulin-dependent diabetics and six non-diabetic laboratory rats. A water-soluble extract of the fruits significantly reduced blood glucose concentrations during a 50 g oral glucose tolerance test in the diabetics and after force-feeding in the rats. Fried karela fruits consumed as a daily supplement to the diet produced a small but significant improvement in glucose tolerance. Improvement in glucose tolerance was not associated with an increase in serum insulin responses. These results show that karela improves glucose tolerance in diabetes. Doctors supervising Asian diabetics should be aware of the fruit's hypoglycaemic properties.

Animals↗

Abnormal plasma glucose and insulin responses in heterozygous lean (ob/+) mice.

To investigate the effect of the ob gene in the heterozygous condition, plasma glucose and insulin responses of adult heterozygous lean (ob/+) mice were compared with mice of the homozygous lean (+/+) and homozygous obese (ob/ob) genotypes. The ob/+ mice consumed 24% more food than +/+ mice although body weights were similar. Plasma glucose and insulin concentrations were respectively 16% and 176% higher in ob/+ mice than +/+ mice in the freely fed state, and 44% and 88% higher during glucose tolerance tests. In 24 hour fasted ob/+ mice, plasma glucose concentrations were 23% higher than +/+ mice but plasma insulin concentrations were not significantly different. Arginine produced a greater insulin response (172%) and a greater fall in glycaemia (200%) in ob/+ mice. A significant difference in the hypoglycaemic effect of insulin in ob/+ and +/+ mice was not observed. These results demonstrate an effect of the ob gene on glucose homeostasis in heterozygous lean (ob/+) mice. The abnormalities were qualitatively similar but considerably less severe than those in ob/ob mice, suggesting that ob/+ mice might prove useful to study factors predisposing to inappropriate hyperglycaemia.

Animals↗

Development of glucose intolerance and impaired plasma insulin response to glucose in obese hyperglycaemic (ob/ob) mice.

The development of glucose intolerance in Aston ob/ob mice showed a gross exaggeration of the age-related changes of glucose tolerance in lean (+/+) mice. Intraperitoneal glucose tolerance in ob/ob mice was poor at 5 weeks, improved by 10 weeks, but markedly worsened by 20 weeks. A 24 hour fast further exaggerated the glucose intolerance of ob/ob mice. Unlike lean mice, tolerance improved in ob/ob mice at 40 weeks. Alterations of insulin sensitivity and the plasma insulin response to glucose accounted in part for these observations. Insulin sensitivity deteriorated until 20 weeks, but improved at 40 weeks in both fed and 24 hour fasted ob/ob mice. A positive plasma insulin response to glucose was lost after 5 weeks in fed ob/ob mice. The severity of this abnormality corresponded with the extent of the basal hyperinsulinaemia. A 24 hour fast reduced plasma insulin concentrations and restored a positive plasma insulin response to glucose in ob/ob mice. The results suggest that the plasma insulin response to glucose in ob/ob mice is related to the secretory activity of the B-cells prior to stimulation. Furthermore, it is evident that factors in addition to insulin insensitivity and the impaired plasma insulin response to glucose contribute to the development of glucose intolerance in these mice.

Aging↗

Role of ovarian hormones in the long-term control of glucose homeostasis, glycogen formation and gluconeogenesis.

The effect of ovarian hormones on in vivo gluconeogenesis and glycogen deposition in liver, uterus, skeletal and cardiac muscle was studied. Ovariectomized adult female mice were treated with replacement doses of estradiol, progesterone, both hormones combined, or vehicle only for 15 weeks. Compared with intact control mice, ovariectomy increased gluconeogenesis and reduced the glycogen content of all tissues examined. Treatment with estradiol and progesterone, individually and in combination, increased tissue glycogen deposition. Estradiol alone consistently produced the greatest effect, except on hepatic glycogen, which was maximally increased by the combined estradiol-progesterone regimen. Estradiol markedly reduced gluconeogenesis, and this effect was antagonized by progesterone. The results indicate that the lower plasma glucose concentrations produced by ovarian steroids result in part from reduced glucose neoformation and greater storage of glycogen in liver and muscle tissues.

Animals↗

Plasma high density lipoprotein cholesterol in streptozotocin diabetic and non-diabetic mice after prolonged administration of glibenclamide, chlorpropamide and metformin.

A possible influence of oral hypoglycaemic drugs on plasma high density lipoprotein cholesterol (HDL-C) concentrations was examined in streptozotocin diabetic and non-diabetic mice. Treatment of streptozotocin diabetic mice with glibenclamide (0.4 mg/kg/day), chlorpropamide (10 mg/kg/day) or metformin (60 mg/kg/day) for 28 weeks did not significantly alter plasma total cholesterol (TC) or HDL-C in streptozotocin diabetic mice. Plasma TC and HDL-C were not related to the prevailing plasma glucose concentration. Non-diabetic mice treated with glibenclamide or metformin for 46 weeks showed no changes in TC or HDL-C. However, chlorpropamide increased TC and HDL-C, and lowered the TC : HDL-C molar ration after 46 weeks in non-diabetic mice. The effect of chlorpropamide was associated with an excessive gain in weight.

Animals↗

A comparative study of two serotypes of epidermolytic toxin from Staphylococcus aureus.

Two serotypes of epidermolytic toxin were purified from culture filtrates of different strains of Staphylococcus aureus. The amino acid composition of the proteins is similar, each containing no cystine and one methionine, but type ii contains no tryptophan, whereas type i has 1 mol/mol protein. The molecular weights of type i and type ii toxins were 30,000 and 29,500, respectively, as found by SDS-polyacryamide gel electrophoresis and confirmed by studies of CNBr fragments and tryptic peptides. Dansylation gave a single different N-terminal amino acid for each toxin; the C-terminus of each is lysine. Peptide mapping of tryptic digests showed that very few peptides are common to the two amino acid sequences.

Amino Acids↗

Role of ovarian hormones in the long-term control of glucose homeostasis. Effects of insulin secretion.

The role of ovarian hormones in the long-term control of B-cell function of in the mouse has been examined. Ovariectomised adult female mice were treated with daily subcutaneous replacement doses of oestradiol (5 microgram/kg), progesterone (1 mg/kg), both hormones combined, or vehicle only for 15 weeks. Ovariectomy caused a 40% increase in plasma glucose concentrations during glucose tolerance tests, a 26% decrease in the plasma insulin response to glucose (2 g/kg IP) and a 32% decrease in the plasma insulin response to arginine (2 g/kg IP) compared with control mice. When islets from ovariectomised mice were incubated for 30 minutes in media containing 28 mmol/l glucose or 2.8 mmol/l glucose with 5 mmol/l arginine, insulin release was reduced by 23% and 31% respectively. Total pancreatic and islet insulin content were each decreased by 36%, and the number of B-cells was decreased by 39% in the ovarietomised mice. These detrimental effects of ovariectomy were partially or totally prevented by the oestradiol and progesterone treatments. The results indicate that ovarian oestrogens and progestogens may play an important role in the long-term maintenance of B-cell competence in the female mouse.

Animals↗

Role of ovarian hormones in the long-term control of glucose homeostasis. Interaction with insulin, glucagon and epinephrine.

This study examines the effects of ovarian hormones on the glycaemic actions of insulin, glucagon and epinephrine. Ovariectomized adult female mice were treated with replacement doses of oestradiol, progesterone, both hormones combined or vehicle only for 15 weeks. Compared with intact control mice, ovariectomy did not significantly alter insulin-induced hypoglycaemia. However, treatment with oestradiol or progesterone alone, but not in combination, increased the hypoglycaemic action of insulin. The hyperglycaemic effect of glucagon and epinephrine was increased by ovariectomy and reduced by the ovarian hormone treatments. The results indicate that oestradiol and progesterone individually synergize the hypoglycaemic action of insulin, but mutually antagonize each other in this respect. Oestradiol and progesterone, individually and in combination, appear to suppress the glycogenolytic action of glucagon and epinephrine.

Animals↗