Decrease In Plasma Glucose Concentration Research Articles

Effects of Ostarine and Endurance Training on Some Functional, Hematological, and Biochemical Parameters in Male Rats

Background: Non-steroidal Selective Androgen Receptor Modulators (SARMs) are currently a group of drug candidates with anabolic effects, tissue selectivity, and the potential to improve the therapeutic process in a number of socially significant diseases. There is insufficient data on their effects during exercise and on their adverse side effects. Objectives: Our objective was to examine the role of selective androgen receptor modulators for the physical working capacity of the body, hematological and biochemical parameters, and to evaluate any side effects of SARMs. We studied the effects of ostarine (S-22, MK-2866, GTx-024, Enobosarm) alone or in combination with submaximal training in sexually mature male Wistar rats. Methods: The rats used were divided into a treadmill-trained group and a sedentary group. Half of each group received either ostarine or vehicle for 8 weeks (n = 10 each). We performed functional tests and blood analysis at the end of the experiment to analyze clinical chemistry and hematological indicators. Results: Ostarine did not affect maximal sprint speed, VO2max, and running economy, while submaximal training increased these parameters. Ostarine increased total plasma cholesterol and energy expenditure and decreased plasma glucose concentration. Neither treatment changed the oxygen-carrying capacity of the blood, the respiratory quotient, the concentration of triglycerides and LDL-cholesterol, or creatine kinase. Combined treatment neutralized the negative effect of ostarine on plasma total cholesterol levels. Conclusions: Ostarine did not affect the examined hematological and physical working capacity parameters, but it changed some clinical chemistry indicators. Training improved the physical working capacity but did not affect the clinical chemistry and hematological parameters. Further research is needed to clarify other aspects of the influence of non-steroidal SARMs on the physical working capacity and possible side effects during long-term use, as their administration, along with physical activity, is becoming popular among healthy adult bodybuilders in gyms.

Interaction of DGAT1 polymorphism, parity, and acetate supplementation on feeding behavior, milk synthesis, and plasma metabolites

Acetate supplementation increases milk fat production, but interactions with animal-related factors have not been investigated. The objective of this study was to characterize the interaction of acetate supplementation with parity and genetic potential for milk fat synthesis including the DGAT1 K232A polymorphism (AA and KA genotypes). In total, 47 primiparous and 49 multiparous lactating cows were used in 2 blocks in a crossover design. The basal diet was formulated to have a low risk of biohydrogenation-induced milk fat depression and had 32.8% and 32.0% neutral detergent fiber and 21.7% and 23.6% starch [all on a dry matter (DM) basis] in block 1 and 2, respectively. The control treatment received the basal diet, and the acetate supplementation treatment included anhydrous sodium acetate supplemented to the basal diet at 3.2% and 3.1% of DM of the diet for block 1 and 2, respectively (targeting 10 mol/d of acetate). The DGAT1 genotype frequency of the experimental cows was 45% AA and 51% KA, with 4% cows with either a KK or unimputable genotype. Acetate supplementation increased DM intake (DMI) in KA multiparous cows, but acetate did not change DMI in AA multiparous or primiparous cows of either genotype. Acetate supplementation increased the frequency of meals by 8% and decreased the length of each meal by ∼5 min compared with control. There was no effect of acetate on milk yield. Acetate supplementation increased milk fat yield and concentration by 117 g/d and 0.31 percentage units, respectively, regardless of DGAT1 polymorphism or parity. The increase in milk fat yield was mostly due to an increase in yield of 16C mixed-sourced fatty acids, suggesting that acetate supplementation drives mammary de novo synthesis toward completion. Response to acetate supplementation was not related to genomic predicted transmitting ability of milk fat concentration and yield or to pretrial milk fat percent and yield, suggesting that acetate increases milk fat production regardless of genetic potential for milk fat yield and level of milk fat synthesis. Interestingly, analyzing the temporal effect on the interaction between treatment and DGAT1 polymorphism on milk fat yield suggested that DGAT1 polymorphism may affect the short-term response to acetate supplementation during the first ≤7 d on treatment. Acetate supplementation also increased plasma β-hydroxybutyrate concentration and decreased plasma glucose concentration. In conclusion, acetate supplementation consistently increased milk fat synthesis regardless of parity or genetic potential for milk fat synthesis.

EVALUATION OF THE ANTIDIABETIC AND ANTIOXIDANT EFFECT OF GARLIC JUICE ON ALLOXAN INDUCE DIABETIC RAT

Medicinal plants may provide valuable therapeutic agents in modern medicine and in traditional system, especially in areas where the modern drugs are unavailable, expensive or predispose to life threatening complications. One of these plants is Garlic (Allium L. liliaceae) which is used as foodstuff, condiment, and flavoring in folk medicine. The aim of this study was to investigate the effect of garlic juice on plasma glucose concentration and superoxide dismutase (SOD) activity on alloxan induced diabetic rats following injection with alloxan (120 mgkg-1 body weight) to diabetic treated and diabetic control group‘s intraperitoneally. Garlic juice (1ml/100g/body weight) was administered orally to diabetic treated once daily for 28 days. The result showed a statistically significant (P<0.05) decrease in plasma glucose concentration of diabetic treated at day 28 (112.86 ±2.10mg/dl) when compared to day 0 (202.09 ± 1.80mg/dl). SOD activity showed a statistical significant increase (P < 0.05) in the liver of diabetic treated when compared to in diabetic control. There was a statistical non-significant increase (P>0.05) in the heart and kidney of diabetic treated when compared to diabetic control. The result obtained in this study showed that garlic juice has antidiabetic and slight antioxidant effect in plasma and tissues (Liver, Heart andKidney

Effects of dietary butyrate supplementation and oral nonsteroidal anti-inflammatory drug administration on serum inflammatory markers and productivity of dairy cows during the calving transition

Dairy cattle experience inflammation during the calving transition period, and butyrate and nonsteroidal anti-inflammatory drugs (NSAID) are expected to reduce the inflammation. Our objective was to evaluate the effects of dietary butyrate supplementation and oral NSAID administration on feed intake, serum inflammatory markers, plasma metabolites, and milk production of dairy cows during the calving transition period. Eighty-three Holstein cows were used in the experiment with a 2 × 2 factorial arrangement of treatments. The cows were blocked by parity and calving date, and randomly assigned to a dietary butyrate or control supplement, and NSAID or a placebo oral administration. Experimental diets were iso-energetic containing calcium butyrate at 1.42% of diet dry matter (DM) or the control supplement (1.04% commercial fat supplement and 0.38% calcium carbonate of diet DM). The close-up diets contained 13.3% starch and 42.4% neutral detergent fiber on a DM basis, and were fed from 28 d before expected calving date until calving. The postpartum diets contained 22.1% starch and 34.1% neutral detergent fiber on a DM basis and were fed from calving to 24 d after calving. Oral NSAID (1 mg of meloxicam/kg of body weight) or placebo (food dye) was administered 12 to 24 h after calving. Dietary butyrate supplementation and oral NSAID administration did not affect milk yield or postpartum serum concentrations of amyloid A and haptoglobin. However, butyrate-fed cows increased plasma fatty acid concentration on d -4 relative to calving (501 vs. 340 μEq/L) and tended to increase serum haptoglobin concentration (0.23 vs. 0.10 mg/mL). There was a supplement by drug interaction effect on plasma glucose concentration on d 4; in cows administered the placebo drug, butyrate supplementation decreased plasma glucose concentration compared with control-fed cows (62.8 vs. 70.1 mg/dL). Butyrate-fed cows tended to have lower milk crude protein yield compared with cows fed the control diet (1.21 vs. 1.27 kg/d). Dietary butyrate supplementation and oral NSAID administration did not have overall positive effects on production performance of dairy cows during the calving transition period.

Milk metabolites as noninvasive indicators of nutritional status of mid-lactation Holstein and Montbéliarde cows

The objective was to investigate the effects of feed restriction on concentrations of selected milk metabolites in mid-lactation Holstein and Montbéliarde cows and to explore their correlations with energy balance and classic plasma and milk indicators of nutritional status. Eight Holstein and 10 Montbéliarde cows (165 ± 21 d in milk) underwent 6 d of feed restriction during which feed allowance was reduced to meet 50% of their net energy for lactation (NEL) requirements. The experiment was divided in 4 periods: control (CON; d -3 to -1), restriction (RES; d 1 to 6), wk 1 (W1; d 7 to 13), and wk 2 (W2; d 14 to 18) after refeeding at ad libitum intake. Intake, milk production, energy balance and plasma metabolites were used to validate the feed restriction model. Concentrations of 7 milk metabolites: β-hydroxybutyrate (BHB), glucose, glucose-6-phosphate, isocitrate, glutamate, uric acid, and free amino groups were measured in morning milk samples, and fatty acids were measured in pooled p.m. and a.m. samples. Feed restriction induced a negative energy balance (-42.5 ± 4.4 MJ/d), increased plasma nonesterified fatty acids and BHB, and decreased plasma glucose concentrations. Feed restriction increased milk glucose-6-phosphate and isocitrate (+38% and +39%, respectively) and decreased milk BHB, glucose, glutamate, uric acid and free amino group concentrations (-20%, -57%, -65%, -42%, and -14%, respectively), compared with pre- restriction. Milk concentrations of medium-chain fatty acids (e.g., sum of C10 to C15) decreased and those of long chain (e.g., 18:0, cis-9 18:1) increased during restriction. Breed differences were not detected for the majority of variables. All studied milk metabolites were significantly correlated with energy balance (Spearman correlation = 0.48, 0.63, -0.31, -0.45, and 0.61 for BHB, glucose, glucose-6-phosphate, isocitrate, and glutamate, respectively). Milk glucose and glutamate showed the strongest correlations with plasma metabolites and milk FA associated with lipomobilization. These results suggest that milk metabolites may be used as noninvasive indicators of negative energy balance and metabolic status of dairy cows.

Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors.

Sodium–glucose cotransport 2 inhibitors (SGLT2i) lower plasma glucose but stimulate endogenous glucose production (EGP). The current study examined the effect of dapagliflozin on EGP while clamping plasma glucose, insulin, and glucagon concentrations at their fasting level. Thirty-eight patients with type 2 diabetes received an 8-h measurement of EGP ([3-3H]-glucose) on three occasions. After a 3-h tracer equilibration, subjects received 1) dapagliflozin 10 mg (n = 26) or placebo (n = 12); 2) repeat EGP measurement with the plasma glucose concentration clamped at the fasting level; and 3) repeat EGP measurement with inhibition of insulin and glucagon secretion with somatostatin infusion and replacement of basal plasma insulin and glucagon concentrations. In study 1, the change in EGP (baseline to last hour of EGP measurement) in subjects receiving dapagliflozin was 22% greater (+0.66 ± 0.11 mg/kg/min, P < 0.05) than in subjects receiving placebo, and it was associated with a significant increase in plasma glucagon and a decrease in the plasma insulin concentration compared with placebo. Under glucose clamp conditions (study 2), the change in plasma insulin and glucagon concentrations was comparable in subjects receiving dapagliflozin and placebo, yet the difference in EGP between dapagliflozin and placebo persisted (+0.71 ± 0.13 mg/kg/min, P < 0.01). Under pancreatic clamp conditions (study 3), dapagliflozin produced an initial large decrease in EGP (8% below placebo), followed by a progressive increase in EGP that was 10.6% greater than placebo during the last hour. Collectively, these results indicate that 1) the changes in plasma insulin and glucagon concentration after SGLT2i administration are secondary to the decrease in plasma glucose concentration, and 2) the dapagliflozin-induced increase in EGP cannot be explained by the increase in plasma glucagon or decrease in plasma insulin or glucose concentrations.

OR20-6 Ketones and Sepsis-Induced Muscle Weakness: Signal or Fuel for Protection?

Background: Septic patients often develop muscle weakness, contributing to ICU morbidity and mortality. We recently observed that obese septic mice and patients do not develop such weakness, explained by increased lipolysis and hepatic conversion of fatty acids into the ketone bodies. Furthermore, in lean septic mice, supplementing nutrition with 3-hydroxybutyrate (3HB) reproduced the protection against muscle weakness seen with obesity. The aim of the current study was to investigate underlying mechanisms of the 3HB-protection. Methods: We performed a mouse study (n=49) in a centrally-catheterized fluid-resuscitated model of prolonged (5 days) abdominal sepsis (cecal ligation and puncture). Lean septic mice received standard parenteral nutrition (PN) supplemented with either D,L-3HB (5 mg/kg/day) or isocaloric glucose (gluc). Healthy pair-fed mice served as controls. The use of 3HB as energy substrate in the muscle was assessed by quantifiying protein, triglyceride and glycogen content and markers of muscle ketolysis, proteolysis and fatty acid oxidation (FAO). Signaling function of 3HB was assessed by markers of muscle autophagy activation, inflammation and regeneration. Results: Although 3HB infusion abated sepsis-induced upregulation of ubiquitin-proteasome system marker Fxbo32 (p=0.002), loss of muscle mass was not prevented (p=0.8). Sepsis reduced triglyceride content (p≤0.01) equally in PN+gluc and PN+3HB mice (p=0.9), but did not affect markers of muscle FAO (Cd36, Cpt1b, Acadl, Hadha mRNA) in PN+gluc and PN+3HB mice (p≥0.2). Muscle glycogen content was unaltered by sepsis (p=0.1), and the illness-induced decrease in plasma glucose concentrations at day 5 (p≤0.004) was similar in PN+gluc and PN+3HB mice (p=1). Gene expression of the ketolysis enzyme Oxct1 was lower in PN+3HB compared to PN+gluc septic mice and healthy controls (p≤0.05). Also, ketone body transporter Mct1 mRNA was elevated by sepsis (p≤0.01) but attenuated by 3HB (p=0.05) compared to glucose. Sepsis-induced elevation of inflammation markers (Tnfα, IL-1β, Nlrp3 mRNA levels; p≥0.4) and autophagy (Atg5, Atg7 mRNA; p≥0.4; LC3 II/I, p-ULK1/ULK1 protein; p≥0.4) were not countered by 3HB infusion compared to glucose. However, PN+3HB septic mice did show enhanced markers of muscle regeneration (Myod1, Myf5 and Myog mRNA; p≤0.04) compared to PN+gluc septic mice and healthy controls. Also, sepsis-induced elevation of expression of Hdac4, an inhibitor of myoblast differentiation stimulator Mef2c, was reduced by 3HB (p=0.03) and resulted in increased Mef2c mRNA levels (p=0.01) compared to glucose. Conclusion: In conclusion, the observed protection against sepsis-induced muscle weakness with 3HB infusion coincided with enhanced markers of muscle regeneration, but not with changes in substrate handling. Supplemented 3HB during sepsis thus acted as a signaling molecule rather than as an energy source.

Substrate metabolism, hormone and cytokine levels and adipose tissue signalling in individuals with type 1 diabetes after insulin withdrawal and subsequent insulin therapy to model the initiating steps of ketoacidosis.

Lack of insulin and infection/inflammation are the two most common causes of diabetic ketoacidosis (DKA). We used insulin withdrawal followed by insulin administration as a clinical model to define effects on substrate metabolism and to test whether increased levels of counter-regulatory hormones and cytokines and altered adipose tissue signalling participate in the early phases of DKA. Nine individuals with type 1 diabetes, without complications, were randomly studied twice, in a crossover design, for 5h followed by 2.5h high-dose insulin clamp: (1) insulin-controlled euglycaemia (control) and (2) after 14h of insulin withdrawal in a university hospital setting. Insulin withdrawal increased levels of glucose (6.1 ± 0.5 vs 18.6 ± 0.5mmol/l), NEFA, 3-OHB (127 ± 18 vs 1837 ± 298μmol/l), glucagon, cortisol and growth hormone and decreased HCO3- and pH, without affecting catecholamine or cytokine levels. Whole-body energy expenditure, endogenous glucose production (1.55 ± 0.13 vs 2.70 ± 0.31mgkg-1min-1), glucose turnover, non-oxidative glucose disposal, lipid oxidation, palmitate flux (73 [range 39-104] vs 239 [151-474] μmol/min), protein oxidation and phenylalanine flux all increased, whereas glucose oxidation decreased. In adipose tissue, Ser473 phosphorylation of Akt and mRNA levels of G0S2 decreased, whereas CGI-58 (also known as ABHD5) mRNA increased. Protein levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase phosphorylations were unaltered. Insulin therapy decreased plasma glucose concentrations dramatically after insulin withdrawal, without any detectable effect on net forearm glucose uptake. Release of counter-regulatory hormones and overall increased catabolism, including lipolysis, are prominent features of preacidotic ketosis induced by insulin withdrawal, and dampening of Akt insulin signalling and transcriptional modulation of ATGL activity are involved. The lack of any increase in net forearm glucose uptake during insulin therapy after insulin withdrawal indicates muscle insulin resistance. ClinicalTrials.gov NCT02077348 FUNDING: This study was supported by Aarhus University and the KETO Study Group/Danish Agency for Science Technology and Innovation.

Effects of the Interation of Metformin and Vernonia amygdalina (Bitter Leaf) On Steptozotocin-Induced Diabetic Rats

The effects of Vernonia amygdalina and metformin in lowering glucose in streptozotocin-induced diabetic rats were evaluated. A total of 120 Wistar albino males and females rats weighing approximately 200 g were used for the study. Diabetes was induced in the rats using 50 mg/kg of streptozotocin, and it was confirmed by checking the glucose levels of the rats. Rats with glucose level greater than 10 mmol/L were considered diabetic. The extract, metformin and a combination of the extract and metformin were given orally to different groups of diabetic rats daily for 10 weeks. Four rats were sacrificed every 2 weeks, and blood samples were collected from all the groups to estimate glucose, total protein and liver enzymes. The data obtained were compared using analysis of variance (ANOVA) and the differences between groups were established using Dunnets. The extract and metformin produced significant (P&lt;0.05) decrease in plasma glucose concentrations in the diabetic rats. There was also a reduction in the plasma glucose of the rats that received a combination of the extract and metformin. The decrease in the blood glucose concentrations of the diabetic rats following the administration of the extract suggests that it possesses hypoglycemic effects on streptozotocin-induced diabetic rats. The presence of flavonoids, saponins and other phytochemicals in the extract must have acted to potentiate the hypoglycemic role of the extract.

DETECTION OF SUBCLINICAL PREGNANCY TOXEMIA AND EVALUATION OF GLYCAEMIC STATUS IN MALABARI DOES

Aim: The aim of the study was to screen Malabari does for subclinical pregnancy toxemia and to evaluate their glycaemic status. Materials and Methods: This study consist of 4 groups; Group I early pregnant does (n = 7), Group II late pregnant does with one fetus (n = 6), Group III late pregnant does with two fetuses (n = 8), and Group IV nonpregnant does (n = 8). The pregnancy was confirmed by 3.5 Megahertz B-mode ultrasonography. The concentration of beta-hydroxybutyrate (BHB) and glucose was analyzed in the blood samples. Results and Discussion: Significant increase in serum BHB concentration was found in Groups I and II when compared to control group. Group III showed highly significant increase when compared to control group. Among the four groups selected, late pregnant animals with two fetuses had a BHB level of 0.81 ± 0.10 mmol/l, which shows that those animals were in subclinical pregnancy toxemic stage. A highly significant decrease in plasma glucose concentration was found in Group I, Group II, and Group III; compared to controls. Hypoglycemia was seen in all the three groups studied. Conclusion: Hyperketonemia not only represents a disease sign but rather acts in a multifunctional way in promoting development of pregnancy toxemia.

МЕТАБОЛІТОТРОПНА ТЕРАПІЯ В ЛІКУВАННІ ПАЦІЄНТІВ ІЗ ГІПЕРТОНІЧНОЮ ХВОРОБОЮ ІІ СТАДІЇ У ПОЄДНАННІ З СТАБІЛЬНОЮ ІШЕМІЧНОЮ ХВОРОБОЮ СЕРЦЯ

In the treatment of arterial hypertension (AH), stable ischemic heart disease (SIHD), correction of metabolic factors of cardiovascular risk using antioxidants and nitrogen monoxide (NO) donor agents is extremely important.The aim of the study – to investigate the effectiveness of treatment of patients with AH of the II stage in conjunction with SIHD by influencing with Quercetin (Corvitin) and Arginine hydrochloride (Tivortin) upon the lipid and carbohydrate metabolism indices, the intensity of peroxide lipid oxidation (LPO), and the endothelial function.Materials and Methods. The study involved 56 patients with AH of the II stage concomitant with SIHD, which were randomized into two groups. The 1st group consisted of 24 patients, who received a common baseline therapy (BT). Patients of the 2nd group (32 persons) received infusion Corvitin therapy (0.5 g) besides BT during the first 6 days, and 100 ml of intravenous Tivortin solution during the next 6 days, followed by the outpatient oral administration of 10 ml of Tivortin 2 times per day during two weeks.Results and Discussion. The use of Corvitin and Tivortin against the background of BT in patients with AH of the II stage in combination with SIHD has led to a significant improvement of lipidogram indices, decreased plasma glucose concentration, immunoreactive insulin (IRI), HOMA -IR index, plasma malonic aldehyde (MA) and erythrocytes. Reliable increase in the content of reduced glutathione (RG), increased activity of glutathione peroxidase (GP), catalase (CT) has been marked from the side of antioxidant protection (AOP). There was a significant increase in the content of end-metabolites of NO by 22.2 %, of the endothelial vascular growth factor VEG F-A – by 38.2 %. A more significant indices dynamics is observed in patients with the genotype Pro/Ala of the PPAR γ2 gene.

Leptin and Leptin Receptor Genes Are Associated With Obesity-Related Traits Changes in Response to Aerobic Training Program.

Leońska-Duniec, A, Jastrzębski, Z, Jażdżewska, A, Krzysztof, F, and Cięszczyk, P. Leptin and leptin receptor genes are associated with obesity-related traits changes in response to aerobic training program. J Strength Cond Res 32(4): 1036-1044, 2018-Leptin (LEP) and leptin receptor (LEPR) genes have been studied for their potential association with development of human obesity and its related complications. Therefore, we have decided to check whether selected body mass, body composition, and metabolic variables observed in physically active participants will be modulated by the polymorphisms. The genotype distribution was examined in a group of 201 women measured for chosen traits before and after the completion of a 12-week aerobic training program. Our results revealed a significant interaction between training and LEP genotype for glucose level. A training-related decrease in plasma glucose concentration in the LEP AG heterozygotes differed significantly from the change in the homozygotes. The polymorphism was also associated with fat-free mass (FFM), total body water (TBW), total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) levels. Another finding was a significant interaction between training and LEPR for LDL-C level. As opposed to AG and GG, AA homozygotes demonstrated a training-related decrease in LDL-C level. Our findings also showed that the LEPR G allele is connected with obesity-related traits. The participants with the GG genotype had higher body mass, body mass index (BMI), FFM, and TBW during the entire study period. This study provides evidence that polymorphisms in the LEP and LEPR genes are associated with the magnitude of the effects of regular physical activity on glucose and LDL-C levels, respectively. In addition, we found the association of the G allele of the LEPR polymorphism with body mass and BMI.

Evolutionarily‐Conserved Mechanisms of Nutrient Acquisition in the Primordial Vertebrate, the Pacific Hagfish

Hagfish occupy the basal position of vertebrate phylogeny and are thus of interest for studies examining the evolution of vertebrate traits. Despite a morphologically basic digestive tract, the carnivorous hagfish can rapidly and effectively acquire nutrients from which they can persist off of for upwards of 11 months. Previous studies indicate that hagfish preferentially utilize carbohydrates and transition into fat‐fuelled energy sources as fasting progresses, yet few studies examine the mechanisms by which hagfish acquire nutrients. The aim of the present study was to examine and characterize the mechanisms of nutrient acquisition in the hindgut of the Pacific hagfish (Eptatretus stoutii), focusing on one molecule from each category of macronutrients: carbohydrates (glucose), fats (oleic acid) and proteins (alanyl‐alanine). Radiotracer fluxes across intestinal tissue demonstrated concentration‐dependent uptake indicative of regulated transport, for glucose (Km 0.37 mM, Jmax 8.48 nmol/cm2/h), oleic acid (Km 55 μM, Jmax 1131 pmol/cm2/h) and alanyl‐alanine (Km 1071 μM, Jmax 70 nmol/cm2/h). Pharmacological inhibition of glucose transporters (34% decrease with 200 μM cytochalasin‐b) and sodium‐glucose linked transporters (52–83% decrease with 0.0001–1μM phlorizin) suggest mechanisms akin to those in mammals exist in the hagfish hindgut. Further similarity in transport arises in that dipeptide transport is dependent upon sodium‐proton exchange, wherein a reduced sodium environment yields a 48% decrease in transport rates. While specific isoforms of mammalian fatty acid transporters demonstrate insulin sensitivity, hagfish oleic acid transport rates were unaffected by insulin application (average rate 2741± 262 pmol/cm2/h, N=10), despite a noted 71% decrease in plasma glucose concentration. Finally, feeding resulted in significant remodeling of the intestinal mucosa with hindgut absorptive microvilli lengthening by 125% post‐feeding. Correspondingly, an increased rate of transport was noted post‐feeding, with the degree of change dependent upon the substrate type. This study reveals evolutionarily‐conserved mechanisms of nutrient transport over a broad range of substrates in the oldest extant vertebrate and solidifies the applicability of hagfish as a model for studies of early vertebrate evolution.Support or Funding InformationSupported by NSERC Discovery Grants to GG (203736) and CG (251083)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS-55) on adiposity and hepatic lipid composition in rat offspring.

Fructose-containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes. Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring. Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning. Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high-sugar diet. Guidelines for maternal nutrition should advise limiting consumption of fructose-containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation. Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or suckling periods on offspring at 3 and 12weeks, utilising a cross-fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3-week-old offspring exposed to sucrose or HFCS-55 during suckling, with increased hepatic fat content in HFCS-55-exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega-7 and -9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and suckling periods, and HFCS-55 offspring exposed during suckling only. By 12weeks, the effects on adiposity and hepatic lipid composition were largely normalised. However, exposure to either sucrose or HFCS-55 during the prenatal period only was associated with elevated plasma free fatty acids at weaning, and this effect persisted until 12weeks. This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring.

Effect of reducing milk production using a prolactin-release inhibitor or a glucocorticoid on metabolism and immune functions in cows subjected to acute nutritional stress.

When cows are unable to consume enough feed to support milk production, they often fall into severe negative energy balance. This leads to a weakened immune system and increases their susceptibility to infectious diseases. Reducing the milk production of cows subjected to acute nutritional stress decreases their energy deficit. The aim of this study was to compare the effects on metabolism and immune function of reducing milk production using quinagolide (a prolactin-release inhibitor) or dexamethasone in feed-restricted cows. A total of 23 cows in early/mid-lactation were fed for 5 d at 55.9% of their previous dry matter intake to subject them to acute nutritional stress. After 1 d of feed restriction and for 4 d afterward (d 2 to 5), cows received twice-daily i.m. injections of water (control group; n=8), 2mg of quinagolide (QN group; n=7), or water after a first injection of 20mg of dexamethasone (DEX group; n=8). Feed restriction decreased milk production, but the decrease was greater in the QN and DEX cows than in the control cows on d 2 and 3. As expected, feed restriction reduced the energy balance, but the reduction was lower in the QN cows than in the control cows. Feed restriction decreased plasma glucose concentration and increased plasma nonesterified fatty acid (NEFA) and β-hydroxybutyrate (BHB) concentrations. The QN cows had higher glucose concentration and lower BHB concentration than the control cows. The NEFA concentration was also lower in the QN cows than in the control cows on d 2. Dexamethasone injection induced transient hyperglycemia concomitant with a reduction in milk lactose concentration; it also decreased BHB concentration and decreased NEFA initially but increased it later. Feed restriction and quinagolide injections did not affect the blood concentration or activity of polymorphonuclear leukocytes (PMN), whereas dexamethasone injection increased PMN blood concentration but decreased the proportion of PMN capable of inducing oxidative burst. Incubation of peripheral blood mononuclear cells in serum harvested on d 2 of the restriction period reduced their ability to react to mitogen-induced proliferation, and injection of quinagolide or dexamethasone could not alleviate this effect. This experiment shows that prolactin-release inhibition could be an alternative to dexamethasone for reducing milk production and energy deficit in cows under acute nutritional stress, without disturbing immune function.

Low, Chronic Exposure to Endosulfan Induces Bioaccumulation and Decreased Carcass Total Fatty Acids in Neotropical Fruit Bats.

We investigated the effects of the insecticide endosulfan on energy metabolism and its possible accumulation in fruit bats. Adult male bats (Artibeus lituratus) were exposed for 35days, when they were offered fruit treated with endosulfan (E) and adhesive spreader (AS) in the following concentrations (g/L): 0.0; 0.0 (Control), 0.0; 0.015 (AS), 1.05; 0.015 (E1), 2.1; 0.015 (E2). Concentrations used were those recommended by the manufacturer for fruit crop application (E1) or twice this value (E2). E1 bats showed decreased plasma glucose concentration. Carcass fatty acids were decreased in E1 and E2 bats. Endosulfan bioaccumulation was observed in both liver and adipose tissues from E1 and E2 bats. These results indicate that the chronic exposure of fruit bats to environmentally relevant concentrations of endosulfan can lead to significant bioaccumulation beyond control and also decreased fatty acid content, which may impair the health of this important seed disperser in neotropical forests.

Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway.

BackgroundType-2 diabetics have an increased risk of cardiomyopathy, and heart failure is a major cause of death among these patients. Growing evidence indicates that proinflammatory cytokines may induce the development of insulin resistance, and that anti-inflammatory medications may reverse this process. We investigated the effects of the oral administration of zinc and acetylsalicylic acid, in the form of bis(aspirinato)zinc(II)-complex Zn(ASA)2, on different aspects of cardiac damage in Zucker diabetic fatty (ZDF) rats, an experimental model of type-2 diabetic cardiomyopathy.MethodsNondiabetic control (ZL) and ZDF rats were treated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 29–30 weeks, the electrical activities, left-ventricular functional parameters and left-ventricular wall thicknesses were assessed. Nitrotyrosine immunohistochemistry, TUNEL-assay, and hematoxylin-eosin staining were performed. The protein expression of the insulin-receptor and PI3K/AKT pathway were quantified by Western blot.ResultsZn(ASA)2-treatment significantly decreased plasma glucose concentration in ZDF rats (39.0 ± 3.6 vs 49.4 ± 2.8 mM, P < 0.05) while serum insulin-levels were similar among the groups. Data from cardiac catheterization showed that Zn(ASA)2 normalized the increased left-ventricular diastolic stiffness (end-diastolic pressure–volume relationship: 0.064 ± 0.008 vs 0.084 ± 0.014 mmHg/µl; end-diastolic pressure: 6.5 ± 0.6 vs 7.9 ± 0.7 mmHg, P < 0.05). Furthermore, ECG-recordings revealed a restoration of prolonged QT-intervals (63 ± 3 vs 83 ± 4 ms, P < 0.05) with Zn(ASA)2. Left-ventricular wall thickness, assessed by echocardiography, did not differ among the groups. However histological examination revealed an increase in the cardiomyocytes’ transverse cross-section area in ZDF compared to the ZL rats, which was significantly decreased after Zn(ASA)2-treatment. Additionally, a significant fibrotic remodeling was observed in the diabetic rats compared to ZL rats, and Zn(ASA)2-administered ZDF rats showed a similar collagen content as ZL animals. In diabetic hearts Zn(ASA)2 significantly decreased DNA-fragmentation, and nitro-oxidative stress, and up-regulated myocardial phosphorylated-AKT/AKT protein expression. Zn(ASA)2 reduced cardiomyocyte death in a cellular model of oxidative stress. Zn(ASA)2 had no effects on altered myocardial CD36, GLUT-4, and PI3K protein expression.ConclusionsWe demonstrated that treatment of type-2 diabetic rats with Zn(ASA)2 reduced plasma glucose-levels and prevented diabetic cardiomyopathy. The increased myocardial AKT activation could, in part, help to explain the cardioprotective effects of Zn(ASA)2. The oral administration of Zn(ASA)2 may have therapeutic potential, aiming to prevent/treat cardiac complications in type-2 diabetic patients.

Glucoregulatory, endocrine and morphological effects of [P5K]hymenochirin-1B in mice with diet-induced glucose intolerance and insulin resistance.

The frog skin host-defence peptide hymenochirin-1B has been shown to stimulate insulin release in vitro from isolated pancreatic islets and BRIN-BD11 clonal β-cells. This study examines the effects of 28-day administration of a more potent analogue [P5K]hymenochirin-1B ([P5K]hym-1B) (75nmol·kg(-1) body weight) to high-fat-fed mice with obesity, glucose intolerance and insulin resistance. Treatment with [P5K]hym-1B significantly decreased plasma glucose concentrations and improved glucose tolerance, insulin secretion, insulin sensitivity and increased the magnitude of the incretin effect (difference in response to oral vs intraperitoneal glucose loads). Responses to established insulin secretagogues were greater in islets isolated from treated animals compared with saline-treated controls. [P5K]hym-1B administration significantly decreased total islet area and β- and α-cell areas, and resulted in lower concentrations of circulating triglycerides and plasma and pancreatic glucagon. Peptide treatment had no effect on food intake, body weight, indirect calorimetry or circulating concentrations of amylase and marker enzymes of liver and kidney function. RT-PCR demonstrated that the Insr (insulin receptor) gene and genes involved in insulin signalling (Slc2a4, Irs1, Pik3ca, Akt1 and Pkd1) were significantly up-regulated in skeletal muscle from animals treated with [P5K]hym-1B. Expression of the Glp1r (GLP-1 receptor) and Gipr (GIP receptor) genes was significantly elevated in islets from peptide-treated mice. These data suggest that [P5K]hym-1B shows potential for development into an agent for treating patients with type 2 diabetes.

Looking at the metabolic consequences of the colchicine-based in vivo autophagic flux assay

ABSTRACTMonitoring autophagic flux in vivo or in organs remains limited and the ideal methods relative to the techniques possible with cell culture may not exist. Recently, a few papers have demonstrated the feasibility of measuring autophagic flux in vivo by intraperitoneal (IP) injection of pharmacological agents (chloroquine, leupeptin, vinblastine, and colchicine). However, the metabolic consequences of the administration of these drugs remain largely unknown. Here, we report that 0.8 mg/kg/day IP colchicine increased LC3-II protein levels in the liver of fasted trout, supporting the usefulness of this drug for studying autophagic flux in vivo in our model organism. This effect was accompanied by a decrease of plasma glucose concentration associated with a fall in the mRNA levels of gluconeogenesis-related genes. Concurrently, triglycerides and lipid droplets content in the liver increased. In contrast, transcript levels of β-oxidation-related gene Cpt1a dropped significantly. Together, these results match with the reported role of autophagy in the regulation of glucose homeostasis and intracellular lipid stores, and highlight the importance of considering these effects when using colchicine as an in vivo “autophagometer.”

Effects of ractopamine hydrochloride and dietary protein content on performance, carcass traits and meat quality of Nellore bulls

Ractopamine hydrochloride (RH) alters protein metabolism and improves growth performance in Bos taurus cattle with high carcass fat. Our objective was to evaluate the effects of RH, dietary CP and RH×CP interaction on performance, blood metabolites, carcass characteristics and meat quality of young Nellore bulls. A total of 48 bulls were randomly assigned to four treatments in a 2×2 factorial arrangement. The factors were two levels of dietary CP (100% and 120% of metabolizable protein requirement, defined as CP100 and CP120, respectively), and two levels of RH (0 and 300 mg/animal·per day). Treated animal received RH for the final 35 days before slaughter. Animals were weighed at the beginning of the feedlot period (day 63), at the beginning of ractopamine supplementation (day 0), after 18 days of supplementation (day 18) and before slaughter (day 34). Animals were slaughtered and hot carcass weights recorded. After chilling, carcass data was collected and longissimus samples were obtained for determination of meat quality. The 9–11th rib section was removed for carcass composition analysis. Supplementation with RH increased ADG independently of dietary CP. There was a RH×CP interaction on dry matter intake (DMI), where RH reduced DMI at CP120, with no effect at CP100. Ractopamine improved feed efficiency, without RH×CP interaction. Ractopamine had no effect on plasma creatinine and urea concentration. Greater dietary CP tended to increase blood urea, and there was a RH×CP interaction for plasma total protein. Ractopamine supplementation increased plasma total protein at CP120, and had no effect at CP100. Ractopamine also decreased plasma glucose concentration at CP100, but had no effect at CP120. Ractopamine increased alkaline phosphatase activity at CP120 and had no effect at CP100. There was a tendency for RH to increase longissimus muscle area, independently of dietary CP. Ractopamine did not alter fat thickness; however, fat thickness was reduced by greater CP in the diet. Supplementation with RH decreased meat shear force, but only at day 0 of aging, having no effect after 7, 14 or 21 days. Greater dietary protein increased meat shear force after 0 and 7 days of aging, with no effect after 14 or 21 days. These results demonstrate for the first time the efficacy of ractopamine supplementation to improve gain and feed efficiency of intact Bos indicus males, with relatively low carcass fat content. Ractopamine effects were not further improved by increasing dietary protein content above requirements.