Increased Plasma Glucose Levels Research Articles

Role of Hepatic Monounsaturated Fatty Acid Synthesis in Metabolic Regulation

Stearoyl‐CoA desaturase (SCD) catalyzes the de novo synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acids. Past work demonstrated SCD1 deficiency impairs hepatic lipogenesis and protects against diet‐induced obesity. Our objective was to determine if hepatic MUFA synthesis is sufficient to restore the impaired lipogenic program in SCD1 global knockout mice (GKO). To address this, we produced liver‐specific transgenic mice expressing either human SCD5, which preferentially synthesizes oleate (18:1n‐9), or mouse SCD3, which preferentially synthesizes palmitoleate (16:1n‐7), and introduced these transgenes into GKO mice. Hepatic oleate synthesis largely prevented very‐low‐fat diet‐induced weight loss and increased white adipose tissue weight to a greater extent than hepatic palmitoleate. In females, hepatic SREBP‐1 maturation and lipogenic gene expression increased in hSCD5/GKO while expression of these genes remained low in mSCD3/GKO mice. Hepatic oleate increased plasma glucose levels greater than hepatic palmitoleate. This work suggests that hepatic MUFA are involved in regulation of lipogenesis and gluconeogenesis with oleate being more potent than palmitoleate. Supported by NIH.

Hydrochlorothiazide exacerbates metabolic syndrome in the SHROB rat model

Metabolic syndrome consists of hypertension, insulin resistance, dyslipidemia and fatty liver. Thiazides are the leading treatment for hypertension, but some clinical studies have suggested adverse metabolic effects. We sought for the first time to characterize the metabolic effects of thiazides in an animal model of metabolic syndrome. SHROB rats are obese, hypertensive and express every component of human metabolic syndrome. Adult female SHROB rats (N=6 per group) were fed a purified diet (AIN 93) replete with electrolytes and treated in their drinking water for 5 weeks with either vehicle (250 ppm saccharine and 100 ppm sodium benzoate) or hydrochlorothiazide (achieved dose of 44±2 mg/kg/d). Systolic blood pressure fell progressively from 184±5 to 142±2 mmHg with thiazide treatment while remaining unchanged in controls. Heart rate was not affected. Body weight, food intake, and water intake did not differ between groups, nor did fasting glucose or insulin. Oral glucose tolerance testing (6 g/kg by gavage after an 18h fast) showed increased plasma glucose levels in the thiazide group (at 60 min post load, 394±48 vs 214±51 mg/dL in controls, P<0.05 by t‐test). Insulin levels at the same time were half again higher in SHROB treated with thiazide (90±20 vs 61±14 ng/mL in controls, NS, but two‐way ANOVA shows a difference, P<0.05 by F‐test). Relative liver mass was increased in the thiazide group relative to controls (43±3 vs 35±3 g/kg body weight, P<0.05 by t‐test). Thus, thiazide was an effective antihypertensive therapy in the SHROB model of metabolic syndrome but worsened glucose tolerance and insulin resistance and enlarged the already fatty liver. The secretory response of the pancreas to glucose was apparently not impaired or even increased, suggesting that insulin signaling may be affected by thiazides.Research support for this study was given by Ophthalmology Education Worldwide

Vitamin D deficiency is a risk factor for obesity and type 2 diabetes mellitus in reproductive age women

Background. Some studies suggest that serum 25(OH) vitamin D level could be associated with fat mass quantity and glucose metabolism parameters. However, the data seem to be contradictory. Objective. We examined the interrelatoins between serum 25(OH)D with body composition, glucose metabolism parameters in healthy women. Design and methods. We examined 320 healthy late reproductive age women (aged 40 to 52 years old, mean age — 46.1 ± 4.5 years). Serum 25(OH)D and insulin levels were determined by ELISA, plasma glucose levels — by standard biochemistry. Insulin resistance was evaluated by HOMA-IR and insulin sensitivity index (ISI-0,120).We used DEX in 134 women to determine fat mass and calculate fat mass index (FMI). Results. Serum 25(OH)D level was from 19.4 to 134.0 nMol/L (mean — 52.9 ± 22.7). Vitamin D insufficiency and deficiency (lower than 75 nMol/L) was revealed in 86.8 % of healthy women. The study showed, that low vitamin D level was associated with obesity (r = -0.35, p < 0.01), increased plasma glucose level after oral glucose tolerance test (OGTT) (r = -0.31, p < 0.01) and decreased insulin sensitivity index (r = -0.28, p < 0.01). We found that Vitamin D level lower than 50 nMol/L was associated with obesity (OR 2.1; CI 95 %) and type 2 diabetes mellitus (OR 1.67; CI 95 %). Conclusion. Our results show that vitamin D deficiency is highly prevalent in the population of healthy women, and low Vitamin D level correlates with high fat mass, postprandial glucose level and decreased tissue insulin sensitivity. Hence, vitamin D insufficiency might possibly be a risk factor for obesity and insulin resistance development leading to type 2 diabetes mellitus.

Effects of fluctuating glucose concentrations on oxidative metabolism of glucose in cultured neurons and astroglia

The objective of the present study was to evaluate the effects of hyperglycemia on glucose metabolism of brain cells. Not only a sustained hyperglycemic state, but also a fluctuating plasma glucose concentration has been implicated in the pathogenesis of diabetic angiopathy. Acutely increasing plasma glucose levels have not been reported to alter glucose utilization of the brain as a whole. In the present study, we examined the effects of chronic (3 weeks) or short-term (24-hour) exposure to a high glucose concentration on the oxidative metabolism of neurons and astroglia. Cells were prepared from Sprague-Dawley rats and cultured in the presence of a high (22 mM) or low (5 mM) concentration of glucose. The high or low glucose media did not alter either the rates of [14C]deoxyglucose phosphorylation (an indicator of total glucose utilization) or [14C]lactate and [14C]pyruvate oxidation (indicators of oxidative glucose metabolism) in neurons. In contrast, chronic or short-term exposure to a high glucose concentration resulted in significant decreases in oxidation of [14C]acetate, an astrocyte-specific reporter molecule, or [14C]lactate and [14C]pyruvate oxidation in the astroglia. Thus, either chronic or short-term increases in the glucose concentration suppressed oxidative metabolism only in astroglia, indicating neuro-protective roles against hyperglycemic brain cell injury in diabetes mellitus. These different responses of neurons and astroglia may also shed new light on brain energy metabolism in diabetic patients with either chronic high or fluctuating plasma glucose concentrations.

Tiliroside, a glycosidic flavonoid, inhibits carbohydrate digestion and glucose absorption in the gastrointestinal tract

Recent studies have reported that tiliroside, a glycosidic flavonoid, possesses anti-diabetic activities. In the present study, we investigated the effects of tiliroside on carbohydrate digestion and absorption in the gastrointestinal tract. This study showed that tiliroside inhibits pancreatic α-amylase (IC₅₀ = 0.28 mM) in vitro. Tiliroside was found as a noncompetitive inhibitor of α-amylase with K(i) values of 84.2 μM. In male ICR mice, the increase in postprandial plasma glucose levels was significantly suppressed in the tiliroside-administered group. Tiliroside treatment also suppressed hyperinsulinemia after starch administration. Tiliroside administration inhibited the increase of plasma glucose levels in an oral glucose tolerance test, but not in an intraperitoneal glucose tolerance test. In human intestinal Caco-2 cells, the addition of tiliroside caused a significant dose-dependent inhibition of glucose uptake. The inhibitory effects of both sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) inhibitors (phlorizin and phloretin, respectively) on glucose uptake were significantly inhibited in the presence of tiliroside, suggesting that tiliroside inhibited glucose uptake mediated by both SGLT1 and GLUT2. These findings indicate that the anti-diabetic effects of tiliroside are at least partially mediated through inhibitory effects on carbohydrate digestion and glucose uptake in the gastrointestinal tract.

Explaining the Increase of Diabetes Prevalence and Plasma Glucose in Mauritius

OBJECTIVESecular trends in the epidemiology of diabetes are best described by studying the same population over time, but few such studies exist. Using surveys from Mauritius in 1987 and 2009, we examined 1) the change in the prevalence of diabetes, 2) the extent to which changes in traditional diabetes risk factors explained the increase, and 3) the change in the distribution of plasma glucose levels over time.RESEARCH DESIGN AND METHODSIndependent population-based surveys were undertaken in Mauritius in 1987 and 2009 using similar methodology in adults aged 20–74 years. Physical measurements and fasting blood samples were taken, and an oral glucose tolerance test was performed at both surveys.RESULTSThe age-standardized prevalence of diabetes in 2009 was 22.3% (95% CI 20.0–24.6) among men and 20.2% (18.3–22.3) among women, representing an increase since 1987 of 64 and 62% among men and women, respectively. Concurrent changes in the distribution of age, ethnicity, waist circumference, BMI, physical activity, smoking, family history of diabetes, and hypertension explained more of the increase in the prevalence of diabetes in men than in women. Increases in plasma glucose (especially fasting glucose) were seen across the population but were greater at the upper levels.CONCLUSIONSIn Mauritius, there has been a marked increase in diabetes prevalence over 22 years. This mainly results from changes in traditional risk factors, leading to population-wide increases in plasma glucose levels. Interventions to control this escalation of diabetes should focus on population-wide strategies.

Magnoflorine from Tinospora cordifolia stem inhibits α-glucosidase and is antiglycemic in rats

Antidiabetic potential of Tinospora cordifolia stem is well proven. In the course of screening of useful α-glucosidase inhibitors, we prepared alkaloid fraction (AFTC) and isolated three isoquinoline alkaloids, namely, jatrorrhizine, palmatine and magnoflorine as active candidates for α-glucosidase inhibition. The enzyme kinetics was studied using sucrose and maltose as substrates. Michaelis–Menten constant (Km) and maximal velocity (Vmax) values were estimated. A significant decrease in Vmax and unaltered Km was observed in case of jatrorrhizine and palmatine (non-competitive inhibition). Magnoflorine was found to increase apparent Km and shown to be reversible, competitive inhibition. The IC50 value as sucrase inhibitor was 36.25, 23.46 and 9.8μg/mL for jatrorrhizine, palmatine and magnoflorine, respectively, and as maltase inhibitor was 22.05, 38.42 and 7.6μg/mL for jatrorrhizine, palmatine and magnoflorine, respectively. In vivo studies were conducted on rats to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.01) by all the three alkaloids at 20mg/kg b.w. Magnoflorine possessed the most potential activity as α-glucosidase inhibitor in vitro and in vivo.

Type 2 Diabetes Is Associated with Reduced ATP-Binding Cassette Transporter A1 Gene Expression, Protein and Function

ObjectiveIncreasing plasma glucose levels are associated with increasing risk of vascular disease. We tested the hypothesis that there is a glycaemia-mediated impairment of reverse cholesterol transport (RCT). We studied the influence of plasma glucose on expression and function of a key mediator in RCT, the ATP binding cassette transporter-A1 (ABCA1) and expression of its regulators, liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor–γ (PPARγ).Methods and ResultsLeukocyte ABCA1, LXRα and PPARγ expression was measured by polymerase chain reaction in 63 men with varying degrees of glucose homeostasis. ABCA1 protein concentrations were measured in leukocytes. In a sub-group of 25 men, ABCA1 function was quantified as apolipoprotein-A1-mediated cholesterol efflux from 2–3 week cultured skin fibroblasts. Leukocyte ABCA1 expression correlated negatively with circulating HbA1c and glucose (rho = −0.41, p<0.001; rho = −0.34, p = 0.006 respectively) and was reduced in Type 2 diabetes (T2DM) (p = 0.03). Leukocyte ABCA1 protein was lower in T2DM (p = 0.03) and positively associated with plasma HDL cholesterol (HDL-C) (rho = 0.34, p = 0.02). Apolipoprotein-A1-mediated cholesterol efflux correlated negatively with fasting glucose (rho = −0.50, p = 0.01) and positively with HDL-C (rho = 0.41, p = 0.02). It was reduced in T2DM compared with controls (p = 0.04). These relationships were independent of LXRα and PPARγ expression.Conclusions ABCA1 expression and protein concentrations in leukocytes, as well as function in cultured skin fibroblasts, are reduced in T2DM. ABCA1 protein concentration and function are associated with HDL-C levels. These findings indicate a glycaemia- related, persistent disruption of a key component of RCT.

Type D personality and metabolic syndrome in a 7-year prospective occupational cohort

ObjectiveType D personality is a combination of high negative affectivity (NA) and high social inhibition (SI). This trait is related to increased mortality and poor health outcomes in patients with cardiovascular diseases, although it is less well-established if Type D personality also poses an increased risk in healthy populations. A potential underlying pathway could include the metabolic syndrome and the combination of abdominal obesity, subnormal levels of triglycerides and HDL-cholesterol, elevated blood pressure, and increased plasma glucose levels. We investigated if Type D personality shows a cross-sectional and longitudinal association with metabolic syndrome in a working population. MethodsPoisson regression and linear regression were used to estimate the association between Type D personality and its subscales (NA) and (SI) with objectively established metabolic syndrome markers in cross-sectional (n=458) and prospective (n=268, 6.3years follow-up) analyses of data from an occupational cohort (mean age=35.9years, SD=11.7; 80% male). ResultsType D personality was neither associated with the metabolic syndrome nor with any of its subcomponents. ConclusionThe present study does not support a role for metabolic syndrome as a mediating mechanism. More research is needed that examines potential pathways linking Type D personality with cardiovascular disease outcomes.

Evidence for a Gut-Brain Axis Used by Glucagon-like Peptide-1 to Elicit Hyperglycaemia in Fish

In mammals, glucagon-like peptide-1 (GLP-1) produces changes in glucose and energy homeostasis through a gut-pancreas-brain axis. In fish, the effects of GLP-1 are opposed to those described in other vertebrates, such as stimulation of hyperglycaemia and the lack of an effect of incretin. In the present study conducted in a teleost fish such as the rainbow trout, we present evidence of a gut-brain axis used by GLP-1 to exert its actions on glucose and energy homeostasis. We have assessed the effects of GLP-1 on glucose metabolism in the liver as well as the glucose-sensing potential in the hypothalamus and hindbrain. We confirm that peripheral GLP-1 administration elicits sustained hyperglycaemia, whereas, for the first time in a vertebrate species, we report that central GLP-1 treatment increases plasma glucose levels. We have observed (using capsaicin) that at least part of the action of GLP-1 on glucose homeostasis was mediated by vagal and splanchnic afferents. GLP-1 has a direct effect in parameters involved in glucose sensing in the hindbrain, whereas, in the hypothalamus, changes occurred indirectly through hyperglycaemia. Moreover, in the hindbrain, GLP-1 altered the expression of peptides involved in the control of food intake. We have elaborated a model for the actions of GLP-1 in fish in which this peptide uses a mammalian-like ancestral gut-brain axis to elicit the regulation of glucose homeostasis in different manner than the model described in mammals. Finally, it is worth noting that the hyperglycaemia induced by this peptide and the lack of incretin function could be related to the glucose intolerance observed in carnivorous teleost fish species such as the rainbow trout.

Abstract 3605: KW-2450, a novel orally-active dual IGF1R/IR inhibitor: Antitumor effects in vitro and in vivo

Abstract KW-2450 is an orally active, multi-kinase inhibitor which inhibits both insulin-like growth factor receptor (IGF-1R) and insulin receptor (IR) with an IC50 of 7.39 nmol/L and 5.64 nmol/L, respectively. KW-2450 also exhibits inhibitory activities (&amp;gt;90% at 100 nmol/L) against several protein tyrosine kinases such as FAK, FLT1, FLT3, JAK2, KDR, TRKA, and Aurora A. KW-2450 inhibited the growth of various types of malignant cells, and the reduction of phosphorylated IGF-1R or IR and their downstream signalling such as phosphorylation of AKT and ERK were observed from 10 to 30 nmol/L in vitro. The PK/PD study of KW-2450 was conducted in a human colon cancer HT-29/GFP xenograft model. The plasma concentrations of KW-2450 were measured by LC/MS/MS method and the phosphorylation status of IGF-1R (P-IGF-1R) and AKT (P-AKT) in tumor tissue were examined by Western blotting. A single oral administration of KW-2450 showed inhibition of P-IGF-1R and P-AKT in tumor tissue in accordance with the increasing plasma concentration and peaked 2 hours after the administration of the drug at doses of 10 to 80 mg/kg. In this model, KW-2450 showed a statistically significant suppression of tumor growth by oral administration at a dose of 40 mg/kg once a day for 14 days. In addition, KW-2450 at a dose of 10 mg/kg showed a potent growth inhibitory activity against a human myeloma KMS-12-BM xenograft model, which is sensitive to the compound in vitro. In mice, KW-2450 induced an increase of plasma glucose levels at 20 mg/kg and higher in a dose-dependent manner. However, the increase in glucose was transient and it returned to normal levels within 2 hours at 20 mg/kg, 4 hours at 40 mg/kg and 8 hours at 80 mg/kg. A similar trend was seen in insulin levels which return to normal levels within 4 hours at 10 mg/kg, 8 hours at 20 and 40 mg/kg, and 24 hours at 80 mg/kg. In summary, these pharmacological studies revealed that KW-2450 could act as a potent and selective dual IGF-1R/IR inhibitor and exert antitumor effects on various types of malignant cells in vitro and in vivo, although this compound shows multi kinase inhibitory activity in a cell free system. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3605. doi:10.1158/1538-7445.AM2011-3605

Effects of long-term supplementation of dairy cow diets with rumen-protected conjugated linoleic acids (CLA) on performance, metabolic parameters and fatty acid profile in milk fat

The supplementation of conjugated linoleic acids (CLA) to the rations of dairy cows represents an opportunity to reduce the content of milk fat. Therefore, CLA have the potential beneficial effect of reducing energy requirements of the early lactating cow. The present study aimed at the examination of long-term and post-treatment effects of dietary CLA intake on performance, variables of energy metabolism-like plasma levels of non esterified fatty acids (NEFA) and ß-hydroxybutyrate (BHB), and fatty acid profile in milk fat. Forty-six pregnant German Holstein cows were assigned to one of three dietary treatments: (1) 100 g/d of control fat supplement (CON), (2) 50 g/d of control fat supplement and 50 g/d of CLA supplement (CLA-1) and (3) 100 g/d of CLA supplement (CLA-2). The lipid-encapsulated CLA supplement consisted of approximately 10% of trans-10, cis-12 CLA and cis-9, trans-11 CLA each. The experiment started 1 d after calving and continued for about 38 weeks, divided into a supplementation (26 weeks) and a depletion period (12 weeks). Over the first 7 weeks of treatment, 11 and 16% reductions in dry matter intake compared to control were observed for the cows fed CLA-1 and CLA-2 supplements respectively. Consequently, the calculated energy balance for these two CLA groups was lower compared to the control. Plasma levels of NEFA and BHB remained unaffected. Later in lactation the highest CLA supplementation resulted in a reduction of milk fat content of 0.7%. However, no reduction in milk fat yield, and accordingly no milk fat depression (MFD), could be shown. The trans-10, cis-12 CLA in milk fat increased with increasing dietary CLA supplementation in a dose-dependent manner. The proportion of C16 in milk fat was decreased by the highest CLA supplementation. With the exception of an increase in plasma glucose level in the CLA-2 group, no post-treatment effects were observed. Overall, under the conditions of the present study no improvement in the calculated energy balance by CLA supplementation could be shown for the entire evaluation period.

The effects of exercise, heat, cooling and rehydration strategies on cognitive function in football players

We investigated the cognitive effects of exercising in the heat on the field players of two football teams in a series of three matches. Different rehydration and cooling strategies were used for one of the teams during the last two games. Cognitive functions were measured before, during and immediately after each football match, as well as core temperature, body mass, plasma osmolality and glucose levels, allowing an estimate of their differential impacts on cognition. The pattern of results suggests that mild-moderate dehydration during exercise in the heat (up to 2.5%) has no clear effect on cognitive function. Instead, plasma glucose and core temperature changes appear to be the main determinants: higher glucose was related to faster and less accurate performance, whereas core temperature rises had the opposite effect. The 50% correlation between plasma glucose and core temperatures observed during exercise in the heat may help to stabilize cognitive performance via their opposing effects. The glucose-like effects of sports drinks appear to be mediated by increased plasma glucose levels, because drinks effects became non-significant when plasma glucose levels were added to the models. The cooling intervention had only a beneficial effect on complex visuo-motor speed.

Effect of Supplementing Different Levels of Chromium Yeast to Diet on Broiler Chickens on Some Physiological Traits

The experiment was conducted at the faculty of agriculture University of Ain Shams-Egypt, from January to March 2008, to study the effect of different levels of chromium yeast (cr-yeast) on broiler chickens on some physiological traits. A total of 450, one-day old unsexed chickens (Cobb) strain were used. The birds were randomly allocated to five treatments with 3 replicates each. The treatments were control (T1), without supplementation, T2, T3, T4 and T5 which were supplemented with 0.5, 1, 1.5 and 2 mg cr-yeast/kg diet respectively. Chromium yeast supplementation treatments caused a significant (p<0.05) increase in plasma glucose levels, while supplemented Cr-yeast at levels of 1 (T3), 1.5 (T4), 2 (T5) mg/kg diet resulted in a significant (p<0.05) increase in total protein and globulin as compared to control group. Also supplemented 0.5 (T2) or 2 (T 5) mg Cr-yeast resulted in a significant (p<0.05) reduction in total lipid in plasma, whereas cholesterol levels which were significantly (p<0.05) decreased when Cr-yeast was supplemented at levels of 1 (T3), 1.5 (T4) and 2 (T 5) mg/kg diet. Although LDL was significantly (p<0.05) decreased when 1.5 (T4) or 2 (T5) mg Cr-yeast was supplemented to the diet. Lymphoid organs percentage which was not affected by dietary supplementation of Cr-yeast except spleen percentage that was significantly (p<0.05) higher in the group that was supplemented with Cr yeast .Chromium level increased in liver, muscle and plasma as levels of supplementation was increased. Protein percentage in the breast and thigh increased significantly (p<0.05) in all chromium supplementation groups as compared to th e control group, while fat percentage in the breast and thigh decrease significantly (p<0.05) when chromium level increased from 1-2 mg/kg diet. It can be concluded that Cr-yeast had a beneficial effect on some of the physiological measurements of broilers under such experimental conditions.

Discovery of Novel Forkhead Box O1 Inhibitors for Treating Type 2 Diabetes: Improvement of Fasting Glycemia in Diabetic db/db Mice

Excessive hepatic glucose production through the gluconeogenesis pathway is partially responsible for the elevated glucose levels observed in patients with type 2 diabetes mellitus (T2DM). The forkhead transcription factor forkhead box O1 (Foxo1) plays a crucial role in mediating the effect of insulin on hepatic gluconeogenesis. Here, using a db/db mouse model, we demonstrate the effectiveness of Foxo1 inhibitor, an orally active small-molecule compound, as a therapeutic drug for treating T2DM. Using mass spectrometric affinity screening, we discovered a series of compounds that bind to Foxo1, identifying among them the compound, 5-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (AS1842856), which potently inhibits human Foxo1 transactivation and reduces glucose production through the inhibition of glucose-6 phosphatase and phosphoenolpyruvate carboxykinase mRNA levels in a rat hepatic cell line. Oral administration of AS1842856 to diabetic db/db mice led to a drastic decrease in fasting plasma glucose level via the inhibition of hepatic gluconeogenic genes, whereas administration to normal mice had no effect on the fasting plasma glucose level. Treatment with AS1842856 also suppressed an increase in plasma glucose level caused by pyruvate injection in both normal and db/db mice. Taken together, these findings indicate that the Foxo1 inhibitor represents a new class of drugs for use in treating T2DM.

Stress alters food intake and glucosensing response in hypothalamus, hindbrain, liver, and Brockmann bodies of rainbow trout

In fish food intake is altered under stress conditions, and in a fish teleost model like rainbow trout food intake is associated with the activity of the glucosensor systems. Thus, we aimed to evaluate the possible interaction of stress with the response of glucosensor mechanisms in rainbow trout. Thus, we subjected rainbow trout (via intraperitoneal injections) to normoglycaemic (control), hypoglycaemic (4 mg.kg -1 bovine insulin) or hyperglycaemic (500 mg.kg -1 glucose body mass) conditions for 5 days under normal stocking density (NSD, 10 kg fish mass·m -3) or stress conditions induced by high stocking density (HSD, 70 kg fish mass·m -3). The experimental design was appropriate since hypoglycemia and hyperglycemia were observed in fish under NSD whereas in normoglycaemic fish HSD induced changes in stress-related parameters similar to those reported in fish literature, such as increased levels of cortisol and glucose in plasma and decreased levels of glycogen in liver. Food intake did not respond to changes in plasma glucose levels in fish under HSD conditions, in contrast with the decreased food intake observed when glucose levels increased in fish under NSD conditions. Moreover, the changes with the increase in plasma glucose levels in parameters involved in glucosensing in liver, Brockmann bodies (BB), hypothalamus, and hindbrain of fish in NSD either disappeared (DHAP and GAP levels, and GK, PK, and GPase activities in liver; glucose, DHAP and GAP levels in BB; glucose and DHAP levels, and GK and PK activities in hypothalamus; glycogen and DHAP levels, and GSase activity in hindbrain) or changed (cortisol levels in plasma; glycogen and GAP levels, and GSase and FBPase activities in liver; GK and PK activities in BB; GK and PK activities in hindbrain) in fish under HSD. Those changes suggest for the first time in fish the existence of an interaction between glucosensing capacity and stress. The readjustment in the activity of glucosensor systems is also associated with changes in food intake resulting in an inability of the fish to compensate with changes in food intake those of circulating glucose levels as observed in fish under non-stressed conditions.

Nutritional and environmental factors affecting plasma ghrelin and leptin levels in rats

We examined which factors suppress the rise of ghrelin secretion under hunger in 16-h-starved rats, and compared the responses of plasma ghrelin and leptin levels to various exogenous and endogenous stimuli in intact rats. Although an acute expansion of the stomach by infusion of 6 ml air or 3 ml water in rats starved for 16 h did not change the level of plasma acyl-ghrelin 3 ml corn starch solution, corn oil, or 20% ethanol significantly decreased it. Vagotomy inhibited suppression by nutrients but not by ethanol. Chronic infusion of ethanol into the stomach for 3 weeks in free-feeding rats caused widespread injury of the stomach mucosa, and increased both plasma ghrelin levels and the number of ghrelin cells. In intact rats, low temperature did not change ghrelin levels, but increased leptin levels. On the other hand, restriction stress decreased plasma ghrelin levels, but had the reverse effect on plasma leptin levels. Although insulin decreased and 20% glucose increased plasma glucose levels, they both decreased plasma ghrelin levels. Insulin elevated plasma leptin levels, but glucose had no effect. These results indicate that 1) acyl-ghrelin secretion from the stomach under fasting condition is suppressed by nutrients but not by mechanical expansion of the stomach; 2) high and low environmental temperature, stress, or administration of insulin reciprocally affect plasma levels of ghrelin and leptin; and 3) an increase of stomach ghrelin cell number and plasma ghrelin levels after chronic ethanol treatment may be involved in restoration of gastric mucosae.

Ninety day repeated gavage administration of Hipphophae rhamnoides extract in rats

Hippophae rhamnoides, is a high altitude plant, possesses immunomodulatory, anti-oxidant, anti-bacterial and adaptogenic activity and is widely used in treatment of various diseases. The present study was designed to ascertain the safety of aqueous extract of H. rhamnoides fruit when administered by gavage to rats for 90 days. Four groups of animals, each consisting of 15 males and 15 females, were adminstered 0, 100, 250, or 500 mg/kg extract, in a single dose/day. There were no treatment related change in mean body weight, organ/body weight ratio, histological, hematological and biochemical parameters studied in rats of either sex administered with extract at any dose evaluated. However, a significant increase in plasma glucose levels was observed in animals supplemented with 250 or 500 mg/kg extract, which returned to normal after a 2-week withdrawal of treatment. These results indicate no adverse effects of extract at a dose of 100 mg/kg body weight/day in rats administered for 90-days. Based on the findings of this study, the NOAEL was 100 mg/kg body weight/day of aqueous fruit extract of seabuckthorn in rats.

Effects of anesthetic protocols on electroejaculation variables of Iberian ibex ( Capra pyrenaica)

The effects of three intramuscular anesthesia protocols – detomidine 190 μg/kg plus ketamine 2 mg/kg, detomidine 270 μg/kg plus ketamine 1.4 mg/kg, and tiletamine 3.4 mg/kg plus zolazepam 3.4 mg/kg – on penis protrusion and ejaculation variables were compared in nine captive Spanish ibex ( Capra pyrenaica) subjected to electroejaculation. Body temperature, heart, and respiratory rates, as well as a number of plasma biochemical variables were also recorded prior to and during anesthesia. The detomidine plus ketamine protocols induced bradycardia and increased respiratory rate. However, the tiletamine/zolazepam protocol did not affect heart and respiratory rates. None of the three protocols caused a substantial change in rectal temperature, yet all protocols caused a significant increase in plasma glucose levels. Differences in anesthetic protocols did not affect sperm quality or quantity. However, choice of anesthetic protocol affected ( P < 0.05) the degree of penis protrusion and the electrical pulse sequence required to achieve ejaculation. Results of this study support a recommendation of detomidine 270 μg/kg plus ketamine 1.4 mg/kg for anesthesia of Spanish ibex undergoing electroejaculation.

Blood Glucose Control and Coronary Heart Disease

Epidemiologic data support the hypothesis of a direct and independent relationship between hyperglycemia and cardiovascular disease. The lack of a clear-cut threshold value in diabetic patients, and the persistence of the relationship in nondiabetic population as well, suggest that glycemia is a continuous variable, similarly to other cardiovascular risk factors. Moreover, increased plasma glucose levels contribute to cardiovascular risk by activating multiple atherogenic mechanisms. In spite of evident plausibility for hyperglycemia as a cardiovascular risk factor per se, intervention data remain controversial. Results of recent large-scale intervention trials, such as ACCORD, ADVANCE, and VADT, seem to undermine the concept that tight glycemic control confers some protection against cardiovascular disease in patients with type 2 diabetes, while maintenance of near-normal glycemic control from earlier stage of the disease and during acute coronary events seems to be more beneficial. However, individualized therapies remain the cornerstone of strategies aimed to reduce cardiovascular risk associated to hyperglycemia.