Traditional plant remedies for diabetes.
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Animals↗
Biomedical subjects
C J Bailey
Publications and source records attributed to C J Bailey.
Immunoreactive gastric inhibitory polypeptide and K cell hyperplasia in obese hyperglycaemic (ob/ob) mice fed high fat and high carbohydrate cafeteria diets.
The effect of diet composition on plasma and intestinal concentrations of immunoreactive gastric inhibitory polypeptide (GIP) and intestinal K cell density was examined in obese hyperglycaemic (ob/ob) mice. The mice were reared from 3 to 11 weeks of age on either stock diet, a high fat (HF) cafeteria diet or a high carbohydrate (HC) cafeteria diet. The HF cafeteria diet increased the concentration of GIP in plasma (75%) and in the intestine (118%) and increased the density (54%) of GIP-secreting K cells in the upper jejunum compared with the stock diet. Plasma and intestinal GIP concentrations were not significantly altered by the HC cafeteria diet, although the density of K cells in the upper jejunum was increased (45%). The extent of hyperglycaemia and hyperinsulinaemia in ob/ob mice was not significantly altered by the HF and HC cafeteria diets. The results indicate that an increased amount of dietary fat chronically stimulates the production and secretion of GIP, and enhances intestinal K cell density in ob/ob mice.
Animals↗
Hormonal modification of the growth and metabolic effects of a transplantable rat insulinoma.
The growth and metabolic effects of a transplantable radiation-induced rat insulinoma were examined in intact male and female New England Deaconess Hospital (NEDH) rats, and in parathyroidectomised or adrenalectomised male NEDH rats. Subscapular transplantation of insulinoma fragments in intact male rats consistently produced a highly vascularised encapsulated tumour associated with hyperphagia, hyperinsulinaemia and hypoglycaemia which progressed to fatal neuroglycopaenic coma by 30 +/- 0.8 days (mean +/- SEM) and 19 +/- 0.5 days for slow-growing and fast-growing tumour sublines respectively (P less than 0.001). In intact female rats transplanted with the slow-growing subline, the onset of hyperphagia was advanced by 4 days and the severity of hyperinsulinaemia and hypoglycaemia increased (21% and 36%; P less than 0.01 and P less than 0.001, respectively), resulting in a 10% decrease of survival time (P less than 0.05) and a 65% reduction of tumour weight (P less than 0.01). Transplantation of the fast-growing subline into parathyroidectomised male rats, which exhibited a 15-24% (P less than 0.05 - less than 0.01) decrease of plasma calcium, did not modify either the growth or metabolic effects of the tumour. In contrast, transplantation of this subline into adrenalectomised male rats decreased survival time by 32% (P less than 0.001) and reduced final tumour weight by 88% (P less than 0.02) without markedly affecting the onset or magnitude of the hyperinsulinaemia. These results indicate that the growth and metabolic effects of the transplantable NEDH rat insulinoma are modified by the presence of ovarian hormones and by adrenal hormones.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma, Islet Cell↗
Gastric inhibitory polypeptide and the entero-insular axis in streptozotocin diabetic mice.
The function of the entero-insular axis and abnormalities of circulating gastric inhibitory polypeptide (GIP) were examined in mice for 40 days after induction of streptozotocin diabetes. Compared with untreated controls, streptozotocin diabetic mice exhibited marked hyperglycaemia and hypoinsulinaemia, with impaired body weight gain, lipoatrophy, hyperphagia, intestinal hypertrophy, polydipsia and renal hypertrophy. Plasma GIP concentrations were elevated in fed but not fasted streptozotocin diabetic mice, and oral fat evoked a greater GIP response than control mice. In spite of marked hyperglycaemia, fat-stimulated GIP release did not raise plasma insulin in streptozotocin diabetic mice. Neither oral nor intraperitoneal glucose produced a significant insulin response in streptozotocin diabetic mice, although oral glucose resulted in a smaller change in glycaemia. The results indicate that streptozotocin diabetes in mice is associated with ineffectiveness of the entero-insular axis, despite elevated GIP concentrations, which are probably mediated through hyperphagia and defective feedback inhibition by insulin on intestinal K cells.
Animals↗
Age effects on glycosylated blood proteins in lean and obese hyperglycaemic (ob/ob) mice.
Glycosylated haemoglobins and glycosylated plasma proteins were measured by affinity chromatography using Glycogel B, in 2-40 weeks old lean (+/+) and Aston obese hyperglycaemic (ob/ob) mice, and compared with changes in glucose concentrations. Lean mice showed an increase in glycaemia at weaning (3 weeks), and a small rise thereafter. In comparison with lean mice, ob/ob mice showed decreased glucose concentrations at 2 weeks, euglycaemia at 3-6 weeks, and hyperglycaemia from 7 weeks. The increases in glycaemia were followed by elevations of glycosylated haemoglobins after 1 week in ob/ob mice and 2 weeks in lean mice. Glycosylated haemoglobins were significantly elevated in ob/ob mice at 8-40 weeks. The glycosylated haemoglobins and glucose concentrations were correlated (r = +0.7; p less than 0.01; n = 96) for all mice studied. There was no correlation between glycosylated plasma proteins and glucose, or between glycosylated plasma proteins and glycosylated haemoglobins. Glycosylated plasma proteins were unchanged with age in lean mice, and were not significantly raised in ob/ob mice. The results indicate that glycosylated plasma proteins are a poor indicator of the glycaemic environment in mice due to their rapid turnover. In contrast, measurement of glycosylated haemoglobins provides a convenient and reliable assessment of blood glucose homeostasis in the preceding 1-2 weeks.
Aging↗
Anorectic effect of metformin in lean and genetically obese hyperglycaemic (ob/ob) mice.
To investigate the effect of metformin (dimethylbiguanide) on food intake, lean and genetically obese hyperglycaemic (ob/ob) mice habituated to a restricted feeding schedule of 3.5 hr daily, received intraperitoneal (i.p.) injections of the drug 15 min before feeding. Fifty mg/kg metformin i.p. did not significantly alter food intake. However, 250 mg/kg metformin i.p. produced a transient anorectic effect in lean mice at 30-60 min, and a more rapid and more protracted anorectic effect in obese mice. Administration of metformin (50 and 250 mg/kg/day) in the drinking water for 15 days did not significantly alter daily food intake in lean and obese mice. The results indicate a mild and transient anorectic effect of a large parenteral dose of metformin in lean and obese mice.
Animals↗
Effect of metformin on glucose metabolism in mouse soleus muscle.
To investigate the antihyperglycaemic effect of metformin (dimethylbiguanide), insulin binding and glucose metabolism were examined in soleus muscles isolated from streptozotocin diabetic mice. Treatment with metformin (250 mg/kg/day orally for 3 weeks) reduced by 39% the severity of streptozotocin-induced hyperglycaemia. Soleus muscles of metformin treated mice showed a 41% increase in total insulin receptor number, and a 20% increase in 3-0-methylglucose uptake at both submaximally and maximally stimulating insulin concentrations. Oxidation of U-14C-glucose to 14CO2 and the formation of 14C-glycogen were increased by 25% and 30% respectively at maximally stimulating insulin concentrations, but not at submaximally stimulating concentrations. Lactate formation was not significantly altered. Maximum activity of hexokinase (EC 2.7.1.1) was increased by 35%, and this effect was independent of insulin. The results suggest that the antihyperglycaemic effect of metformin in streptozotocin diabetic mice is related in part to an increase in insulin-mediated glucose uptake and oxidative metabolism in skeletal muscle.
Animals↗
Hydrogen exchange kinetics and the mechanism of reaction B of yeast tryptophan synthase.
It has been shown that yeast tryptophan synthase (L-serine hydro-lyase (adding indoleglycerol-phosphate) EC 4.2.1.20) catalyses tritium exchange reactions between protons on the alpha-carbon of L-serine of L-tryptophan, and water. The absolute rates of these reactions and indole-serine condensation (reaction B), all of which are pyridoxal phosphate-dependent, were measured. L-Serine exchange was resolved into two components, a high-affinity, slow, Michaelian reaction (KmS,H = 0.06 mM, kcats,H 3 X 10(-3) s-1) and a faster reaction (kcat greater than 2.5 S-1) which was not saturated even at 100 mM L-serine. Hydrogen exchange by tryptophan was a Michaelian process (KmT,H = 2.9 mM; kcatT,H = 0.6 s-1). Indole did not inhibit either exchange reaction. A plausible explanation of the results, that reaction B has a ping-pong mechanism with serine as first substrate and water and L-tryptophan as first and second products, respectively, was inadequate because of the observations that L-tryptophan is as first and second products, respectively, was inadequate because of the observations that L-tryptophan is synthesised with less than 1 mol of exchanged proton per mol amino acid, and that the ratio kcat/Km for serine changes between enzyme reactions. A branched modification with two enzyme-serine complexes, only one of which will exchange protons with water, will fit all the results.
Carbon Radioisotopes↗
Determination of unsulfonated aromatic amines in FD&C Yellow No. 6 by the diazotization and coupling procedure followed by reversed-phase high-performance liquid chromatography.
Data are presented for the determination of parts-per-billion (10(9)) levels of aniline, benzidine, 4-aminobiphenyl (4-ABP) and 4-aminoazobenzene in the regulated color additive FD&C Yellow No. 6. The determination involves chloroform extraction of the amines from the color additive, followed by diazotization and coupling with the disodium salt of 3-hydroxy-2,7-naphthalenedisulfonic acid (R-salt). The coupling products are then analyzed by reversed-phase high-performance liquid chromatography. An interference discovered during the determination of 4-ABP required the use of 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-1H-pyrazole-3-carboxylic acid (pyrazolone-T) as an alternative coupling agent. The identity of each coupling product is confirmed by obtaining a UV-visible spectrum of the eluting solute. The liquid chromatograph is calibrated in the presence of the color additive by using the external standard method.
Amines↗
Effects of fatty acid chain length and saturation on gastric inhibitory polypeptide release in obese hyperglycaemic (ob/ob) mice.
Plasma gastric inhibitory polypeptide (GIP) responses to equimolar intragastrically administered emulsions of fatty acids (2.62 mmol/7.5 ml/kg) were examined in 18 h fasted obese hyperglycaemic (ob/ob) mice. Propionic acid (C3:0), a saturated short-chain fatty acid, and capric acid (C10:0), a saturated medium chain fatty acid, did not significantly stimulate GIP release. However, the saturated long-chain fatty acid stearic acid (C18:0), and especially the unsaturated long-chain fatty acids oleic (C18:1), linoleic (C18:2) and linolenic (C18:3) acids produced a marked GIP response. The results show that chain length and to a lesser extent the degree of saturation are important determinants of fatty acid-stimulated GIP release. The GIP-release action of long-chain, but not short-chain, fatty acids may be related to differences in their intracellular handling.
Animals↗
Islet cell surface antibodies in genetically obese hyperglycaemic (ob/ob) mice.
A quantitative method for circulating islet cell surface antibodies (ICSA), based on the binding of 125I-protein A to insulin-producing RINm5F cells, was used to evaluate ICSA in plasma of 4- to 40-week-old Aston obese hyperglycaemic (ob/ob) mice and normal control (+/+) mice. RINm5F cells bound 2502 +/- 1196 c.p.m. 125I-protein A per 10(5) cells (mean +/- S.D., n = 54) after incubation with +/+ plasma. ICSA positive plasma (defined as 125I-protein A binding, mean +/- 2 S.D. of +/+ plasma) was detected in 3 out of 54 +/+ mice and 3 out of 54 ob/ob mice. ICSA were not observed in ob/ob mice before the onset of diabetes (7 weeks of age), but were detected at 9, 20 and 40 weeks. At 20 weeks 125I-protein A binding produced by ob/ob plasma was 35% greater than +/+ plasma (P less than 0.05). The low occurrence of ICSA in ob/ob mice (6%) suggests that factors other than ICSA are responsible for B-cell dysfunction and eventual islet degeneration observed in Aston ob/ob mice.
Aging↗
Insulinotropic effect of ovarian steroid hormones in streptozotocin diabetic female mice.
To investigate the protective effect of ovarian sex steroids against streptozotocin diabetes, groups of ovariectomized streptozotocin diabetic female mice were treated orally with estradiol-17 beta (5 and 500 ug/kg/day) or progesterone (1 mg/kg/day) for 10 weeks. Streptozotocin produced a more severe hyperglycaemia and a greater fall in plasma insulin concentrations in ovariectomized mice than intact female mice. The estradiol-17 beta and progesterone treatments reduced both the severity of the hyperglycaemia and the fall in plasma insulin. Loss of pancreatic insulin after streptozotocin administration was reduced in intact mice and in mice treated with estradiol-17 beta. These observations suggest that ovarian sex steroids reduce the severity of streptozotocin diabetes at least partly by countering the cytotoxic effect of the drug on the islet B-cells, thereby reducing the fall in pancreatic and plasma insulin.
Animals↗
Postreceptor effect of metformin on insulin action in mice.
To investigate the possibility that metformin (dimethylbiguanide) modifies insulin-mediated glucose metabolism by an effect that is independent of insulin receptor binding, glycogenesis and insulin binding were measured in soleus muscles isolated from streptozocin diabetic mice after treatment with 60 mg kg-1 metformin daily for 10 weeks. This dose of metformin increased insulin-stimulated glycogenesis but did not affect insulin binding in the soleus muscles of streptozocin diabetic mice. The results suggest that metformin can influence postreceptor sites of insulin action independently of insulin receptor binding.
Animals↗
Effects of natural and synthetic estrogens and progestins on glycogen deposition in female mice.
Glycogen deposition and glucose tolerance were examined in female mice after 24 days of oral treatment with natural (17 beta-estradiol and progesterone) and synthetic (ethinyl estradiol and norethisterone acetate) sex steroids, administered individually and in estrogen-progestin combination. Doses were 5 micrograms/kg/day for estrogens and 1 mg/kg/day for progestins. Compared with diestrus control mice, each treatment increased glycogen deposition in liver, uterus, heart and biceps femoris muscle. 17 beta-Estradiol produced the greatest increments. Progesterone produced considerably smaller increments and antagonized the glycogenic effects of 17 beta-estradiol. Ethinyl estradiol and norethisterone acetate generally induced similar changes in glycogen deposition. Treatments containing 17 beta-estradiol improved glucose tolerance. Although glucose tolerance was not significantly altered by the other sex steroid treatments, the changes in glycogen deposition indicate important effects on tissue carbohydrate metabolism.
Animals↗
Effect of ovarian hormones on glucose metabolism in mouse soleus muscle.
The effects of ovarian steroid hormones on insulin binding and insulin-stimulated glucose metabolism were studied in soleus muscles isolated from groups of ovariectomized adult female mice treated orally for 10 weeks with replacement doses of 17 beta-estradiol (E2) (5 micrograms/kg X day) and progesterone (P) (1 mg/kg X day) alone and in combination. Groups of intact and ovariectomized mice were also treated with placebo. Total muscle insulin binding at 0.17 nM insulin was reduced by 32% in ovariectomized mice, and this effect was partially reversed by each of the sex steroid treatments. Ovariectomy was associated with a decrease (29%) in insulin-stimulated 2-deoxyglucose uptake, while E2 alone produced a 2-fold increase in insulin-stimulated 2-deoxyglucose uptake, glucose oxidation, and glycogenesis. P alone did not significantly alter these parameters of glucose metabolism, but P antagonized the effects of E2 when the two hormones were administered in combination. The results provide evidence that E2 promotes insulin-mediated glucose uptake and utilization in skeletal muscle. The data also indicate that E2 and P exert different effects at postreceptor sites of the insulin effector pathway.
Animals↗
Immunoreactive neurotensin in spontaneous syndromes of obesity and diabetes in mice.
Immunoreactive neurotensin was measured in plasma and acid-ethanol extracts of brain, intestine and pancreas of obese hyperglycaemic (ob/ob) mice of the Aston strain, C57BL/KsJ diabetes-obese (db/db) mice, and their respective lean controls. In lean mice, the intestine was the major source of neurotensin (156-194 mg/g wet weight and 169-361 ng/intestine), with smaller amounts in the brain (33-43 ng/g and 13-17 ng/brain), pancreas (0.8-1.1 ng/g and 0.28-0.32 ng/pancreas) and plasma (50-100 pg/ml). Compared with lean controls, ob/ob and db/db mice exhibited 13 and 23% decreases in brain weight, and 37 and 82% increases in intestinal weight. Concentrations of neurotensin in plasma and brain were similar in lean and obese-diabetic mutant mice, but the total content of brain neurotensin was 25% lower in ob/ob mice. Neurotensin was unchanged in the pancreas of db/db mice. However, raised concentrations and total contents of neurotensin were observed in the pancreas of ob/ob mice (72 and 57%, respectively) and the intestine of both ob/ob (56 and 118%) and db/db (35 and 144%) mice. These observations raise the possibility that increased neurotensin concentrations might exert local effects in the intestine and pancreas which contribute to the pathogenesis of obesity-diabetes syndromes in mice.
Animals↗
Cerasee, a traditional treatment for diabetes. Studies in normal and streptozotocin diabetic mice.
Cerasee, a wild variety of Momordica charantia is traditionally prepared as a tea for the treatment of diabetes mellitus in the West Indies and Central America. To investigate a possible hypoglycaemic effect, concentrated aqueous extracts of cerasee were administered to normal and streptozotocin diabetic mice. In normal mice, intraperitoneal administration of cerasee improved glucose tolerance after 8 hr, and in streptozotocin diabetic mice the level of hyperglycaemia was reduced by 50% after 5 hr. Chronic oral administration of cerasee to normal mice for 13 days improved glucose tolerance. The cerasee extracts did not significantly alter plasma insulin concentrations, suggesting that cerasee may exert an extrapancreatic effect to promote glucose disposal.
Administration, Oral↗
Influence of administration route and treatment duration on the glucoregulatory effects of sex steroids in female mice.
Glucose tolerance and plasma insulin concentrations were determined in intact female mice treated orally, subcutaneously and intramuscularly for 4 and 24 days with estradiol-17 beta (5 micrograms/kg/day), ethinyl estradiol (5 micrograms/kg/day) and progesterone (1 mg/kg/day). Estradiol-17 beta improved glucose tolerance and raised plasma insulin concentrations. These effects were generally greater after the longer treatment period and the s.c. administration route produced the greatest improvement in glucose tolerance with the smallest increase in plasma insulin. Ethinyl estradiol produced qualitatively similar effects to estradiol-17 beta, but quantitatively smaller. Progesterone raised plasma insulin concentrations after the longer treatment period, notably with oral and intramuscular administration, although glucose tolerance was not significantly altered. The results demonstrate the important influence of administration route and treatment duration on the changes in glucose homeostasis induced by sex steroids.
Administration, Oral↗