Effects of single or combined induction of diabetes mellitus and knee osteoarthritis on some biochemical and haematological parameters in rats.

Clinical evidences on the coexistence of diabetes mellitus (DM) and osteoarthritis (OA) dated back to the 1960s. Therefore, the study investigated the effects of induced DM and/or knee osteoarthritis (KOA) on some biochemical and haematological parameters in adult male Wistar rats. Twenty rats were used for this study. They were randomly divided into 4 groups (N=5 rats) which included: Normal control; Osteoarthritic (OA) control; Diabetic control; and, Diabetic+Osteoarthritic (D+OA) control. DM was induced in overnight fasted rats by the administration of streptozotocin (65mg/kg b.w., i.p.) 15min after the administration of nicotinamide (110mg/kg, b.w., i.p.). However, KOA was induced by the intra-articular injection of 4mg of sodium monoiodoacetate in 40µl of normal saline. In the D+OA group, KOA was induced about 12h after the induction of DM. The rats were left untreated for four weeks. Afterwards, the experiment was terminated. The results showed that both DM and OA featured hypercortisolism and dyslipidaemia. The additive effects of both conditions were observed on the lipid profile and some haematological indices in the D+OA group. Unlike DM, OA had mild adverse effects on the haematological profile. Nevertheless, it significantly contributed to hyperglycaemia in the D+OA group, even though it had no significant effect on the insulin resistance. However, the hypocalcaemic and glycogenolytic effects of DM were negated by OA. In conclusion, the coexistence of DM and OA presents a greater challenge on the biochemical and haematological profiles than the individual disease. But, this prediction could sometimes be annulled by the intervention of endogenous homeostatic mechanisms.

Insulin-like growth factor 2 and the insulin receptor, but not insulin, regulate fetal hepatic glycogen synthesis.

Whether insulin or IGFs regulate glycogen synthesis in the fetal liver remains to be determined. In this study, we used several knockout mouse strains, including those lacking Pdx-1 (pancreatic duodenal homeobox-1), Insr (insulin receptor), and Igf2 (IGF-II) to determine the role of these genes in the regulation of fetal hepatic glycogen synthesis. Our data show that insulin deficiency does not alter hepatic glycogen stores, whereas Insr and Igf2 deficiency do. We found that both insulin receptor isoforms (IR-A and IR-B) are present in the fetal liver, and their expression is gestationally regulated. IR-B is highly expressed in the fetal liver; nonetheless, the percentage of hepatic IR-A isoform, which binds Igf2, was significantly higher in the fetus than the adult. In vitro experiments demonstrate that Igf2 increases phosphorylation of hepatic Insr, insulin receptor substrate-2, and Akt proteins and also the activity of glycogen synthase. Igf2 ultimately increased glycogen synthesis in fetal hepatocytes. This increase could be blocked by the phosphoinositide 3-kinase inhibitor LY294008. Taken together, we propose Igf2 as a major regulator of fetal hepatic glycogen metabolism, the insulin receptor as its target receptor, and phosphoinositide 3-kinase as the signaling pathway leading to glycogen formation in the fetal liver.

Glabridin from Chinese herb licorice inhibits fatigue in mice.

The inhibiting effect of glabridin from Chinese herb Licorice on fatigue was investigated in male BALB/c mice. Mice were divided into the following 4 experimental groups: control group (CG), low dose group (LG), middle dose group (MG) and high dose group (HG,). The control group was given 0.5% Tween 80 solution and the treatment groups (LG, MG, HG) were given various doses of glabridin (5, 10, 20 mg/kg) for 28 consecutive days. Body mass, blood lactic acid (BLA), serum blood urea nitrogen (BUN), liver glycogen and muscle glycogen concentrations in mice were determined. Results showed that glabridin significantly inhibited fatigue, which extended the exhaustive exercise time of mice, effectively delayed the elevation of blood lactic acid and increase in the storage of liver and muscle glycogen.

Sources of hepatic glucose production by 2H2O ingestion and Bayesian analysis of 2H glucuronide enrichment.

The contribution of gluconeogenesis to hepatic glucose production (GP) was quantified after (2)H(2)O ingestion by Bayesian analysis of the position 2 and 5 (2)H-NMR signals (H2 and H5) of monoacetone glucose (MAG) derived from urinary acetaminophen glucuronide. Six controls and 10 kidney transplant (KTx) patients with cyclosporine A (CsA) immunosuppressant therapy were studied. Seven KTx patients were lean and euglycemic (BMI = 24.3 +/- 1.0 kg/m(2); fasting glucose = 4.7 +/- 0.1 mM) while three were obese and hyperglycemic (BMI = 30.5 +/- 0.7 kg/m(2); fasting glucose = 7.1 +/- 0.5 mM). For the 16 spectra analyzed, the mean coefficient of variation for the gluconeogenesis contribution was 10% +/- 5%. This uncertainty was associated with a mean signal-to-noise ratio (SNR) of 79:1 and 45:1 for the MAG H2 and H5 signals, respectively. For control subjects, gluconeogenesis contributed 54% +/- 7% of GP as determined by the mean and standard deviation (SD) of individual Bayesian analyses. For the lean/normoglycemic KTx subjects, the gluconeogenic contribution to GP was 62% +/- 7% (P = 0.06 vs. controls), while hyperglycemic/obese KTx patients had a gluconeogenic contribution of 68% +/- 3% (P < 0.005 vs. controls). These data suggest that in KTx patients, an increased gluconeogenic contribution to GP is strongly associated with obesity and hyperglycemia.

Maternal low protein diet restricted to the preimplantation period induces a gender-specific change on hepatic gene expression in rat fetuses.

It has been shown previously that maternal low protein diet (LPD) throughout rat gestation altered hepatic gene expression and enzyme activities in offspring. Here, we investigate the effect of maternal LPD (9% casein vs. 18% control) exclusively during the preimplantation period (switched diet group) or provided throughout gestation on hepatic gene expression in day 20 fetuses. Using quantitative competitive PCR, we found that switched diet induced a two-fold increase (P = 0.008) in hepatic gene expression of phosphoenolpyruvate carboxykinase (PEPCK, a rate limiting enzyme for gluconeogenesis) in male fetuses and a 17% increase (P = 0.005) in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1, acts primarily as a reductase to produce active glucocorticoid) in female liver compared with control fetuses. Maternal LPD administered throughout gestation increased 11beta-HSD1 expression in male fetal liver by 27% (P = 0.042) compared with controls. However, maternal LPD fed for either period did not affect fetal hepatic insulin receptor (IR), glucocorticoid receptor (GR), glycogen synthase (GS) nor placental glucose transporter 1 (Glut1) and 3 (Glut3) transcript levels. The alteration in fetal hepatic gene expression could not be attributed specifically to known regulators including insulin or glucose concentrations in fetal blood nor alteration in cAMP in fetal liver, although a combination of these regulatory factors may be responsible. Fetal hepatic glycogen level was unaffected by maternal diet. The present findings show that the long term potential of the preimplantation embryo is sensitive to maternal LPD such that basal levels of hepatic gene expression in day 20 fetuses are altered in a gender-specific manner.

Anti-fatigue activity of a triterpenoid-rich extract from Chinese bamboo shavings (Caulis bamfusae in taeniam).

The anti-fatigue activity of a pentacyclic triterpenoid extract from bamboo shavings (EBS) from the bark of bamboo (Bambusa tuldoides Munro), was evaluated in BALB/c mice. EBS, isolated by the supercritical CO(2) fluid extraction (SFE) technique, was given to mice at concentrations of 0.04 (low-dose group), 0.08 (middle-dose group) and 0.25 g/kg body weight (high-dose group). The anti-fatigue activity of EBS was estimated by the change in body weight, weight-loaded swimming test and climbing test, and corresponding parameters including serum urea nitrogen, hepatic glycogen and blood lactic acid were measured. The results showed that an appropriate level of EBS could prolong the weight-loaded swimming and climbing time, and had an active effect on the serum urea nitrogen, hepatic glycogen and blood lactic acid level in BALB/c mice, which significantly embodied the anti-fatigue activity of EBS. Overall, it is predicted that EBS, being a composition mainly containing a group of pentacyclic triterpenoids, and its main triterpenoid components have great potential for application in relevant fields for its anti-fatigue activity.

Effects of the antithyroid agent propylthiouracil in a partial life cycle assay with zebrafish.

Some ubiquitous pollutants of the aquatic environment, such as PCBs or other polyhalogenated aromatic hydrocarbons, may disrupt the thyroid hormone system. In a partial life cycle assay with zebrafish (Danio rerio), we studied the effects of the reference compound propylthiouracil (PTU) on reproduction, growth and development, histopathology of some target tissues, and plasma thyroid hormone levels. PTU induced a concentration-dependent increase of egg production with a concomitant decrease of mature oocyte size but had no effect on fertilization rate or hatching. In F1, serious dysmorphogenesis was found in 4 dph larvae at the highest PTU level tested (100 mg/L), and there was a dose-dependent decrease in body length and weight at 42 dph (significant at 100 mg/L PTU). At this time, there was also a decreased scale thickness, suggesting inhibited metamorphosis, detectable at 1 mg/L PTU and higher. PTU also induced activation of the thyroid follicles in a concentration-dependent way, in juveniles associated with hyperemia in the thyroid area, and depletion of liver glycogen. Effects in adults were associated with decreased circulating levels of the thyroid hormones T3 and T4. These observations indicate that disruption of the thyroid hormone system may affect the fitness of these aquatic organisms. The zebrafish model may contribute to the identification of thyroid hormone disrupting activity in water samples and also in the interpretation of histological observations in free-ranging fish species.

Effects of inducing physiological hyperglucagonemia on metabolic responses to exercise.

The purpose of the present study was to assess the effects of exogenously increasing the circulating levels of glucagon on the metabolic responses to exercise in rats. A total of six groups of rats were infused (iv) either with glucagon (20 or 50 ng x kg(-1) x min(-1)) or saline (0.9% NaCl), either in the resting state or during a bout of running exercise (45 min, 26 m x min(-1), 0% grade). Blood samples were taken at the end of the 45-min experiment. Animals infused with glucagon at 50 ng x kg(-1) x min(-1) showed significantly (P<0.01) higher mean plasma glucagon concentrations than animals infused with saline or glucagon at 20 ng x kg(-1) x min(-1). In addition, exercise resulted in significantly (P<0.05) higher mean plasma glucagon concentrations, compared to rest, in all groups. In spite of these differences in glucagon concentrations, there were no significant (P>0.05) effects of exercise and glucagon infusion on mean hepatic glycogen, plasma glucose, insulin, C-peptide, beta-hydroxybutyrate, or catecholamine concentrations. Although exercise resulted in a significant (P<0.01) increase in plasma glycerol and free fatty acid concentrations and a significant (P<0.05) decrease in glycogen in the soleus muscle, these responses were not affected by the glucagon infusion. These results suggest that the liver is non-responsive to physiological hyperglucagonemia in a short-term (45 min) exercise situation.

[Cryopreserved substance, isolated from human fetal liver, restore biochemical processes in acute liver failure]. / Kriokonservirovannye preparaty, vydelennye iz pechenploda cheloveka, vosstanavlivaiut biokhimicheskie protsessy pri ostroi pechenochnoi nedostatochnosti.

Recovery processes dynamics in liver when treating experimental acute hepatic insufficiency (AHI) of various etiology by using cryopreserved biopreparations, obtained from human embryo liver of different terms of development (10-12 weeks), human fetuses (22-24 week of development).

Adrenomedullar catecholamine liberation and carbohydrate metabolism during the first 30 min of an aggressive encounter in rats.

The correlation between adrenomedullar catecholamine secretion and metabolic events was investigated in previously isolated fighting male rats. Aggressive encounters were stopped before the apparition of a dominance order. Aggression consisted of short bursts of reciprocal bites, threatening behavior, and short pauses intercalated. After 30 min of fighting, the percent of catecholamine-stained adrenomedullar cells was reduced significantly in fighters. Fighters showed a significant reduction in liver glycogen, while their blood glucose was increased. Muscle-free glucose showed no statistically significant changes compared to controls, while muscle glucose consumption increased. In the muscle of fighting rats, glycogen content was decreased. Our results demonstrated that there is an adrenomedullar activation in early stages of aggression, the changes in carbohydrate metabolism being in correlation with the catecholamine activation.

Effect of exercise during pregnancy and dam age on maternal blood chemistry and fetal growth.

In order to determine the effect of maternal exercise on maternal nutritional status and fetal growth, young (Y = 45-50 days old) Wistar rats were divided into 4 groups of 5 to 8 animals: control pregnant (CP), control non-pregnant (CNP), exercise-trained (swimming 1 h/day, 5 days/week, for 19 days) pregnant (TP) and exercise-trained non-pregnant (TNP). Four equivalent groups of adult rats (A = 90-100 days old) were also formed. Serum glucose, total protein, albumin, hematocrit and liver glycogen were determined in female rats and pups. There were no statistical differences in serum glucose, total protein and albumin levels, litter size or birth weight among exercise-trained animals, controls and their respective pups. Hematocrit was significantly lower in pups of exercise-trained young rats than in all other groups (YCP = 38.6 +/- 3.0; YTP = 32.6 +/- 2.1; ACP = 39.0 +/- 2.5; ATP = 39.2 +/- 2.9%). Liver glycogen levels were lower in pregnant than in non-pregnant rats but similar in exercise-trained and control rats of the same age and physiological status (YCNP = 4.1 +/- 0.2; YCP = 2.7 +/- 0.9; YTNP = 4.9 +/- 0.8; YTP = 2.7 +/- 0.4; ACNP = 6.1 +/- 0.6; ACP = 3.1 +/- 0.8; ATNP = 6.6 +/- 0.8; ATP = 2.2 +/- 0.9 mg/100 mg). We conclude that pups of adult female rats are spared from the effects of this kind of exercise training during pregnancy. On the other hand, it appears that maternal adaptations to exercise training in young rats are able to preserve only some aspects of pup metabolism.

Contribuiçäo ao estudo do glicogênio hepático em animais (Rattus norvergiccus albinus) tratados cronicamente con cânhamo da India / Contribution to the study of hepatic glycogen in animals (Rattus norvergicus albinus) chronically treated with the hump plant

O presente trabalho avalia o nível de glicogênio hepático em animais tratados cronicamente com cânhamo da India, injetados diariamente por via intraperitoneal. Em trabalhos anteriores observa-se que esses animais apresentam hipoglicemia e näo esclarecem o fator determinante de tal alteraçäo. O objetivo deste trabalho, portanto, é determinar histologicamente possíveis alteraçöees á nível hepático, a fim de se verificar uma possível correlaçäo com a alteraçäo glicêmica

Different effects of subcutaneous D,L-3-hydroxybutyrate and acetoacetate injections on food intake in rats.

Cumulative food intake following subcutaneous injection of D,L-3-hydroxybutyrate (DL3HB) or acetoacetate (AcAc) was investigated in rats, because ketone bodies might contribute to food intake regulation according to Kennedy's lipostatic hypothesis. In addition, the metabolic effects of DL3HB-injections were studied by measuring the levels of plasma D3HB, plasma non-esterified fatty acids (NEFA), plasma glycerol, blood glucose, and liver glycogen. Subcutaneously injected DL3HB (10 mmoles/kg body weight) significantly reduced feeding while equimolar AcAc did not. DL3HB-injection increased plasma D3HB and decreased plasma NEFA and plasma glycerol 1-2 hours after the injection but did not affect blood glucose or liver glycogen content. The data suggest that oxidation of D3HB to AcAc contributes to the inhibition of feeding following subcutaneous DL3HB-injection in rats.

Chronic valproate administration reduces fasting ketonemia in children.

We previously found that chronic administration of sodium valproate to suckling infant mice reduced plasma beta-hydroxybutyrate levels but had no effect on plasma free fatty acid or glycerol concentrations. We now report that valproate has a similar effect in children taking the drug for epilepsy. In larger doses, valproate also depleted the infant mouse liver glycogen content. These findings may relate to the hepatic toxicity of valproate. We advise caution if the drug is being considered for use in chronically malnourished children or when the caloric intake of normal children is likely to be reduced during periods of acute illness.

Subcellular responses of hepatocytes to diabetes in control-fed rats.

The biochemistry and ultrastructure of hepatocytes from streptozotocin-diabetic rats adapted to a controlled feeding schedule are described. The microsomal enzyme glucose-6-phosphatase (G-6-Pase), required for glucose release from the hepatocyte was monitored in homogenate preparations at times after the initiation of feeding in rats trained to a 6 h feeding, 18 h fasting cycle. G-6-Pase specific activity which is increased in ad lib fed diabetic rats was not further increased with time after the initiation of feeding in the feeding trained animals. However, the known elevation in G-6-Pase latent activity of the diabetic rat was reduced during the feeding cycle of times of minimum and maximum plasma glucose. Enzyme latency is a reflection of the multicomponent nature of G-6-Pase activity; therefore, plasma glucose levels may influence elements of that multicomponent system. Hepatic rough and smooth endoplasmic reticulum (RER + SER) fractions from the diabetic animals exhibited high and equivalent G-6-Pase specific activities independent of feeding or fasting. Ultrastructural observations of periportal hepatocytes showed a high content of SER correlated with the high G-6-Pase specific activity and closely associated with dispersed particles of glycogen at all times after the initiation of feeding. Also, an increase in SER was observed in the fasted normal animals although particulate glycogen was nearly absent. These findings support earlier work indicating that diabetes stimulates the proliferation of hepatic SER and that the membranes of this organelle are altered from those of the normal animal.

Dietary fat and exercise conditioning effect on metabolic parameters in the horse.

Four isocaloric diets containing 4, 8, 12 and 16% dietary fat (as soybean oil) were fed to four horses at four intervals according to a Latin square design. After 3 weeks of conditioning at each interval, diet effects were evaluated by trotting all horses at 3.2 m/sec for 6 hours. Pre- and posttrotting responses were measured in muscle and liver glycogen, serum long-chain fatty acids, serum electrolytes, serum enzymes, serum cholesterol, plasma glucose, packed cell volume and hemoglobin. Dietary fat was highly correlated with exercise-induced plasma glucose changes and with cholesterol concentrations. Regardless of the diet, linoleate concentration was about eight times higher than that of the other fatty acids, and it increased slightly as dietary fat levels increased. Stearate concentration also increased with increasing dietary fat but palmitic and oleic acid decreased. Increases in fat intake also resulted in slight increases in liver glycogen at the resting level. Conditioning resulted in a significant decrease in exercise-induced fluctuations of serum enzymes and electrolytes but significantly increased elevations of plasma long-chain fatty acid concentrations. Resting muscle glycogen increased by 37% during the study as a result of conditioning, but there was no effect on liver glycogen at rest or after exercise. Feeding of the four levels of dietary fat in the form of soybean oil had no adverse effects and proved a safe and efficient method of providing concentrated energy to working horses.

The modifying effect of nutritional intake of the posttraumatic depletion in hepatic glycogen in rats.

Hepatic glycogen levels were measured in rats both on oral food ad libitum and where intravenous nutrition was supplied at 0.1, 0.2, and 0.35 Kcal/gm of body weigh/day at 24 and 72 hours after injury. While on oral food rats with a closed femoral fracture had a lower level (25 +/- 6.5 mg/gm of liver) than normal (66 +/- 9.1 mg/gm of liver, P less than 0.005), 24 hours after injury. There was a corresponding rise in blood sugar (161 +/- 20 leads to 240 +/- 23 mg/100 ml, P less than 0.005) at 24 hours. However the food intake fell (23.8 +/- 1.5 leads to 16.6 +/- 2.4 gm/day, P less than 0.01) during the first 24 hours after the injury. When intravenous nutrition was given at a caloric level of 0.35 Kcal/gm/day, hepatic glycogen levels were above normal and there was no difference between injured and noninjured animals. At 0.2 Kcal/gm/day there was also no difference between injured and noninjured animals, but glycogen levels fell from norman levels (78 +/- 12.9 mg/gm) to lower levels (33 +/- 11.9 mg/gm, P less than 0.01) over the 24-hour to 72-hour period. Low levels of caloric intake (0.1 Kcal/gm/day) resulted in a fall in glycogen level in both injured and noninjured animals, with the decrease being significantly greater in the injured animals. It is concluded that maintenance of the caloric intake of rats at normal or high levels via the intravenous route can prevent the depletion of hepatic glycogen produced by a femoral fracture.

Carbohydrate metabolism in the fetal pig during late gestation.

In acute experiments on pregnant sows under sodium pentobarbitone anaesthesia, acid base balance, oxygenation and plasma metabolite concentrations were well maintained in the dam and all fetuses which remained undisturbed in utero, irrespective of the duration of the experiment. Fetal liver glycogen concentrations were also unaffected by the time of removal of the fetus. By contrast, intravascular catheterization and withdrawal of blood led to fetal hyperglycaemia and depletion of hepatic glycogen although blood gas and pH values were not changed by these procedures. In the 1 1/2--2 h sampling period following catheterization the normal positive umbilical venous-arterial differences in plasma glucose and lactate generally became reversed. These changes were prevented by the administration of hexamethonium (10--15 mg . kg-1 i.v.) but the drug did not block the fall in hepatic glycogen in catheterized fetuses. Both adrenaline and noradrenaline, which were each infused intravenously at 2.7--3.9 or 0.6--0.9 microgram . kg-1 . min-1, resulted in fetal hyperglycaemia and lacticacidemia together with a fall in arterial blood pH; hepatic glycogen concentrations in these fetuses were also reduced. The apparent sensitivity of the glycogenolytic mechanism to surgical trauma and haemorrhage in the fetal piglet is discussed in relation to findings in other species.