bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoglycemic effect of leucine in diet‐induced obese SD rat
Authors: Kwon Hye Jin , Park Hoon Jung , Kim Mi Kyung 
Published: June 2021

The aim of this study was to examine the hypoglycemic effect of leucine (Leu) in 6 month‐old Sprague‐Dawley (n=80) rats. One group of 10 rats was fed control diet (control group) and another group of 70 rats was fed a high‐fat diet for 14 wks (high‐fat group) to induce obesity. Ten rats of each group were killed at this stage and the remaining obese rats were then randomly blocked into 6 groups, according to body weight and raised with experimental diets containing different Leu levels (0g, 0.6g, 1.2g /kg BW) and dietary fat level (4%, 20%, w/w) for 5 wks. The levels of fasting blood glucose and fasting plasma insulin and glucagon were measured. HOMA‐indexes were calculated using fasting blood glucose and plasma insulin concentrations. The level of fasting blood glucose and HOMA‐indexes in 1.2g/kg Leu groups were significantly lower than 0g/kg Leu groups, and the levels of plasma insulin and glucagon in 1.2g/kg Leu groups were tended to be lower than 0g/kg Leu groups. In conclusion, the feeding of Leu might have hypoglycemic effect in diet‐induced obese SD rats.* This work was supported by Sungshin Cement Co., Ltd. of Seoul, Korea and the second stage of the Brain Korea 21 project in 2008.
Effect of high saturated‐fat diets on bone mass and endochondral ossification in healthy growing rats
Authors: Macri Vanesa , Juiz Natalia , Gonzales Chaves Macarena , Ponce Graciela , Lanata Eduardo , Rodríguez Patricia , Mandalunis Patricia , Zeni Susana , Friedman Silvia 
Published: June 2021

High‐fat diets can produce deleterious effects on bone metabolism in growing animals. Objective: To investigate in healthy growing rats the effect of high saturated‐fat diets on bone mass and endochondral ossification. Weaning male Wistar rats (n=20) were fed ad libitum one of the 2 diets, for 4 wks: control (C; fat=7% w/w) (AIN‐93G) or a high‐fat diet containing 20% w/w of beef‐tallow (BT). Then rats were sacrificed. Total skeleton bone mineral density (BMD) and bone mineral content (BMC) were evaluated by DXA (Lunar DPX‐L).The following histomorphometric parameters were evaluated: Bone volume (BV/TV)(%) and cartilage growth plate thickness (CGP.Th).Statistics: Student's t test & Pearson's correlations coefficients were calculated. Results (as mean±SD): BMD(mg/cm2), C=245±13 vs BT=244±13 (p>0.05); BMC(mg), C=1085±319 vs BT=689± 224; (BV/TV)(%), C=45±5 vs BT=38±3 (p<0.03); total GPC.Th(mm), C=0.44±0.04 vs BT=0.43±0.03 (p>0.05); proliferative zone GPC.Th(mm), C=0.21±0.01 vs BT=0.18± 0.01 (p>0.001).The correlation between BMC vs proliferative zone CGP.Th was ‐0.881 (p<0.05).ConclusionHigh saturated‐fat diets lead to a decreased in BMC associated with a significant increased in CGP.Th as well as a reduction in BV/TV. Based on these findings, we suggest that high saturated‐fat diets acts as a dependent risk factor for bone modeling interfering the acquired of bone mass. Awarded by UBACyT O 008 ‐ O015.
PLASMA ADENOSINE DEAMINASE ACTIVITY IN A GROUP OF CHILDREN SUFFERING CYSTIC FIBROSIS.PRELIMINARY STUDY.
Authors: Perris Paula , Feliu Maria Susana , Slobodianik Nora 
Published: June 2021

Mucus of children suffering cystic fibrosis (CF) can avoid the normal absorption of essential nutrients and fat, leading to poor digestion, and increased vulnerability to infections. Preliminary results suggest that nutritional status of children suffering CF was altered. Therefore, some authors have observed increase in the activity of sera Adenosine Deaminase (ADA) in patients with pathologies related with lymphocytes T. In this preliminary paper we analyze if plasma ADA activity on this population in nutritional risk, is altered.The study included 17 children of both genders with CF (2months‐10 years old); the activity of ADA (U/L) was determined by the method of Giusti and Galanti; data were compared with the age‐matched well nourished control (C ) applying the test of Student. The results expressed as X+ SD were: CF: 34.5±15.6* ;C: 23.0±5.6 (p< 0.001). It was observed an statistical increase in the activity of ADA. These preliminary results suggest depression on the mechanisms of defense that are concomitant with an altered nutritional status. ADA determination might be included in the periodic evaluation of patients with CF. In these patients, the assessment of nutritional status must be included between the main parameters that could influence the evolution of the disease, the prognosis and the survivalPartially supported by University of Buenos Aires (B074)
Regulation of c‐Jun N terminal kinase (JNK) signaling by dual specificity phosphatases (DUSPs) in adipocytes during inflammatory stress
Authors: Ferguson Bradley Scott , Nam Heesun , Hopkins Robin G , Morrison Ron F 
Published: June 2021

Chronic inflammation is an important element of pathogenic mechanisms linking obesity to diabetes. Mounting evidence strongly suggests that the JNK signaling pathway plays a central role in mediating the inflammatory process as mice deficient in JNK activity are protected against diet‐induced or genetic models of insulin resistance. While numerous studies have examined the upstream signaling on JNK activation, few have addressed the role of JNK deactivation and its effect on biological outcome. Evidence now indicates a critical role for DUSPs in the deactivation of JNK and other signaling pathways. Using 3T3‐L1 adipocytes stimulated with tumor necrosis factor α (TNFα) as a model of inflammation, we examined the role of DUSPs on JNK deactivation and inflammatory function. We show that the transient activation (<1h) of JNK signaling in response to TNFα is prolonged (>2h) in the presence of transcriptional inhibition with actinomyosin D suggesting a role for inducible phosphatases. Based on these data, we identified DUSPs expressed in preadipocytes and show that dusp1, dusp8, and dusp16 are induced in response to TNFα. Of these, dusp8 and dusp16 are regulated by JNK in a negative feedback manner. Focus on kinase‐phosphatase relationships will increase our knowledge governing the inflammatory process that couples obesity to insulin resistance. Supported by NIH (5R21DK072067‐02).Grant Funding SourceNIH 5R21DK072067‐02
Arginine supplementation improves insulin resistance in obese adolescents
Authors: Verbruggen Sascha , Coss‐Bu Jorge , Hsu Jean W‐Ch , Joosten Konrad , van Goudoever Johanness , Castillo Leticia 
Published: June 2021

Arginine through a NO mediated mechanism improves insulin resistance in type 2 diabetes. To asses the effect of a short‐term (1 week) dietary arginine supplementation on insulin resistance in glucose intolerant obese adolescents, we conducted a randomized, cross‐over study in 12 subjects (16±1 yr.;BMI 36±5 kg/m2) receiving a one week diet period of a weight maintaining protein and energy intake, or an isocaloric arginine supplemented (21 gram/day) isonitrogenous diet. At the end of each diet period they received a primed, constant, 7 hr. tracer infusion of [1‐13C]Glucose, L‐[2H3]Leucine and [2H5]Glycerol. During the last 3 hours a hyperinsulinemic euglycemic clamp (HEC; 40 mU·m−2·min−1 insulin) was conducted. Arginine supplementation improved (p<0.05) insulin sensitivity from 0.3±0.2 to. 0.4±0.2 μmol ·kg−1 ·min−1/μU/mL. There was a trend towards improvement of non‐oxidative glucose disposal (3.5±3 vs. 4.5±2 mg.kg−1.min−1; p=0.06). However, there was no effect on endogenous glucose production (‐1.0±1 vs. ‐1.0±2 mg.kg−1.min−1; p=0.99). Arginine had no effect on protein breakdown or lipolysis. A one week oral arginine supplementation (21 gr/day) in obese adolescents improves insulin resistance.NIH DK‐62363, T32 HD‐007445, Ajinomoto 3‐ARP; USDA/ARS 25337387;Sophia Foundation for Scientific Research (SSWO).
Modeling and pathway analysis of [U‐13C]starch conversion by a colonic microbiota
Authors: de Graaf Albert Arjaan , Venema Koen , Maathuis Annet , de Waard Pieter , Deutz Nicolaas 
Published: June 2021

We study colonic microbial diversity, metabolic function of colonic microbes, the way diet affects metabolic fluxes, and how produced metabolites affect human health. Short chain fatty acids (SCFA) and especially butyrate, produced by the colonic microbiota, are important mediators of health and disease. Linking the biosynthesis of SCFA to specific gut microbial pathways holds promise for the development of prebiotics that specifically modulate these pathways in vivo. Therefore, 13C stable isotope labeling, NMR, and mathematical modeling of isotopomer distributions were employed to investigate colonic microbial metabolic pathway activities during [U‐13C]starch conversion in an in vitro model of the colon inoculated with a standardised fresh human fecal microbiota. GC‐MS, enzymatic methods and NMR at 500 MHz were used to identify microbial metabolites and to analyze their 13C contents.The SCFA acetate, propionate and butyrate were determined as the principal starch degradation products. Quantitative insight in bacterial metabolic routes was obtained from analysis of 13C‐13C coupling patterns in 2D HSQC spectra that resulted from incorporation of intact 13C glucose backbone fragments in SCFA. These indicated that e.g. propionate was almost exclusively formed via the succinate pathway.In conclusion, this stable isotope study underlines the importance of colonic bacterial SCFA metabolism.
Sex differences in neuronal nitric oxide synthase (nNOS) expression in the paraventricular nucleus (PVN) and subfornical organ (SFO) in angiotensin II (ANG II)‐induced hypertension
Authors: Singh Minati , Xue Baojian , Hay Meredith , Johnson Alan Kim 
Published: June 2021

Previous studies from our laboratory have shown that there are sex differences in ANG II‐induced hypertension. ICV infusion of L‐NAME augments the pressor effects of long‐term infusions of ANG II in female mice but not in males. However, the mechanisms underlying these sex differences in ANG II‐induced hypertension are not well understood. The present study tested the hypothesis that there is differential expression of nNOS in response to systemic infusions of ANG II in male vs female mice and that this may contribute to sex differences in ANG II‐induced hypertension. We used both intact and gonadectomized male and female mice that were either treated with ANG II (800 ng/kg/min; sc) or vehicle. Following 7 days of ANG II infusion, total cellular protein was isolated from tissue punches of the PVN and SFO and analyzed for the protein nNOS. Western blot analysis of total nNOS protein expression indicated significantly higher levels of nNOS in the PVN and SFO in intact females with or without ANG II treatment when compared to intact males. Under basal conditions, nNOS protein was reduced by gonadectomy in females and increased by gonadectomy in males. Gonadectomized animals did not increase nNOS after ANG II treatment. These results suggest that increased nNOS protein associated with the presence of female gonadal hormones plays a protective role against ANG II‐induced hypertension in female mice.(Support: NIH HL‐59676, HL‐62261, HL‐14388, & DK‐66086)
Effects of Stanniocalcin in the Nucleus of the Solitary Tract (NTS) on Arterial Pressure (AP)
Authors: Ciriello John , Moreau Jason M. , Oiamo Tor , Wagner Graham F. 
Published: June 2021

Stanniocalcin‐1 (STC‐1) is a glycoprotein hormone that decreases cytosolic Ca++ in neurons. A decrease in Ca++ availability to NTS neurons decreases AP. Therefore, the possibility exists that STC‐1 may function in NTS to regulate Ca++ availability of neurons involved in AP regulation. In the first series of experiments, the distribution of STC‐1 receptors in the dorsal vagal complex (DVC) was investigated by in situ ligand binding using a STC‐1‐alkaline phosphatase fusion protein. STC‐1 binding sites were found on neurons throughout the DVC, although most were on neurons of the medial NTS (mNTS). In the second series, microinjection of STC‐1 (1.76‐176 nM; 20 nl) into mNTS in anesthetized rats elicited a dose‐related decrease in AP. On the other hand, neither STC‐1 given iv nor injections into NTS of STC‐1 conjugated to GTP elicited AP responses. The STC‐1 evoked depressor response was due to sympathoinhibition as it was blocked by iv hexamethonium bromide. Finally, microinjection of an STC‐1 primary antibody (100 nl) bilaterally into STC‐1 responsive sites in NTS not only blocked the STC‐1 induced depressor response but also elicited a long lasting increase in AP. Taken together these data suggest that STC‐1, through receptor mediated effects, is involved in altering the excitability of NTS neurons that function as components of neuronal systems controlling AP.Supported by HSFO and CIHR
Endothelium‐dependent contraction induced by acetylcholine in the chicken ductus arteriosus: involvement of a cyclooxygenase‐derived TP receptor agonist
Authors: Villamor Eduardo , Schuurman Marijn J , Zoer Bea , Cogolludo Angel L , Perez‐Vizcaino Francisco 
Published: June 2021

In numerous vascular beds, acetylcholine (ACh) evokes the simultaneous release of endothelium‐derived relaxing and contracting factors (EDRF and EDCF, respectively). We aimed to determine whether ACh evokes the release of an EDCF in the chicken ductus arteriosus (DA) and to identify its nature. Isolated rings of the DA from 19‐d chicken fetuses (total incubation: 21‐d) were mounted in a myograph. Low concentrations of ACh (30 nM‐ 1 µM) elicited a relaxation, which was followed by a contraction at higher concentrations (3 μM ‐0.1 mM). Both relaxation and contraction were abolished by removal of endothelium and were sensitive to the antimuscarinic agents atropine and 4‐DAMP (M3‐receptor antagonist). ACh‐induced relaxation was impaired in the presence of the nitric oxide (NO) synthase inhibitor L‐NAME and the soluble guanylate cyclase (sGC) inhibitor ODQ. ACh‐induced contraction was impaired in the presence of the nonselective inhibitor of cyclooxygenase (COX) indomethacin, the selective COX‐1 inhibitor valeryl salicylate, and the thromboxane A2 (TP) receptor blocker SQ‐29458, whereas the response was not affected by the selective COX‐2 inhibitor nimesulide, the thromboxane synthase inhibitor furegrelate, or the H2O2 scavenger PEG‐catalase. We conclude that in the chicken DA, stimulation of muscarinic receptors by ACh induces an endothelium‐dependent relaxation followed by an endothelium‐dependent contraction. The relaxation involves the NO‐sGC pathway, whereas the contraction involves a COX‐1 product that stimulates TP receptors.Supported by "Fundaci ónde Investigación Médica Mutua Madrileña".
A Role For TNF‐α in Hypertension During Systemic Lupus Erythematosus
Authors: Venegas‐Pont Marcia , Glover Porter H. , LaMarca Babbette D. , Jones Allison V. , Ryan Michael J. 
Published: June 2021

Systemic Lupus Erythematosus (SLE) is an independent risk factor for developing hypertension. The inflammatory cytokine TNF‐α has been implicated in the pathology of hypertension and SLE, perhaps through increased oxidative stress. We tested whether the TNF‐α antagonist etanercept (ETAN) reduces mean arterial pressure (MAP) and protects the kidney in a female mouse model of SLE (NZBWF1). Thirty week old SLE and control mice (NZW/LacJ) received ETAN (0.8mg/kg SC weekly x 4 weeks) or vehicle. Mice with SLE were hypertensive compared to controls. Treatment with ETAN reduced MAP in SLE but not control mice. Treatment with ETAN also reduced the albuminuria associated with SLE. Renal cortex NADPH oxidase activity was higher in SLE mice compared to controls and lowered in SLE mice treated with ETAN. Interestingly, the pathognomonic Anti‐dsDNA antibodies were increased in ETAN treated SLE mice. These data suggest that TNF‐α, through increasing renal oxidative stress, is an important factor in the development of SLE hypertension. (Supported by HL 08597 MJR)*p< 0.05 vs. Ctrl †p<0.05 vs. SLE+Veh
Effects of diabetes over RAS enzymes and peptides of non‐obese diabetic mice mesangial cells
Authors: Colucci Juliana Almada , Candido Georgia Orsi , Pacheco‐Silva Alvaro , Irigoyen Maria Claudia , Casarini Dulce Elena 
Published: June 2021

AimWe studied the balance between different components of the RAS in NOD mice mesangial cells.Methodsprimary culture of mesangial cells, ACE and NEP activity, western blotting, IHC, angiotensins and bradykinin measurement and blood pressure and heart rate analysis.Results and conclusionsACE activity was higher in the diabetic group comparing to normoglycemic (0.23 vs 0.11 μM/min.mg). On the other hand NEP activity was diminished (0.09 vs 0.22 μM/min.mg), maybe indicating a prevalence of constriction mechanisms. Through IHC we observed an intense ACE stain on diabetic group kidney slices, in opposite to what is described in literature for other diabetic mouse models. The angiotensin peptides levels were not significantly altered between both groups, but the BK levels were higher on diabetic animals (3.6 vs 1.7 nmol/mL). An interesting finding was that MBP (83.70 vs 110.81 mmHg) and HR (346.02 vs 591.38 bpm) of diabetic mice was lower than that of non diabetic littermates. On this mouse model, the RAS seem to account for a constrictor effect which may lead to kidney damage associated to diabetes. The most surprising data was the decreased blood pressure, despite the ACE activity augmentation. We suggest that an alternative path may be acting in order to avoid blood pressure raise, which could probably be ACE2, yet to be fully characterized by us on this mouse model. Fapesp (04/15875‐3)
Short‐term Caloric Restriction Improves Glucose Tolerance in Older Mice Independent of Changes in SIRT‐1
Authors: Rippe Catarina , Lesniewski Lisa A , Donato Anthony J , Seals Douglas R 
Published: June 2021

In rodents, life‐long caloric restriction (CR) preserves in vivo glucose‐insulin function with aging, possibly by increasing the protein deacetylase sirtuin 1 (SIRT‐1). Because life‐long CR is not feasible in humans, we determined if short‐term CR could improve glucose‐insulin function in old mice and the role of SIRT‐1. Old (30 mo) male B6D2F1‐mice were fed either ad libitum (AL, n=4‐6) or were restricted to 70% of AL for 5 weeks after 2 weeks of progressive restriction (CR, n=4‐6). At baseline, no differences were observed in the area under the curve (AUC) for glucose or insulin during an i.p glucose tolerance test between AL and CR. The AUC for glucose was not significantly different after vs. before CR (10,085±211 vs. 11,844±1371 mg/dl*min, P=0.1) or AL (12,720±1343 vs. 12,486±1085, P=0.9). However, the AUC for insulin was 77% lower after CR (34±8 vs. 149±22 ng/ml*min, P<0.05), but was 77% greater after AL (234±34 vs. 132±12, P<0.05). CR did not affect SIRT‐1 protein expression in either skeletal muscle or white adipose tissue (WAT) (P=0.9 and P=0.8, post CR vs. AL), but increased expression of insulin receptor substrate‐1 (IRS‐1) by 190% in muscle (2.8±0.6 vs. 1.0±0.2, P<0.05) and by 150% in WAT (2.5±1.0 vs. 1.0±0.4, P<0.005). Our findings indicate that short‐term CR markedly improves insulin sensitivity in old mice independent of changes in peripheral SIRT‐1 expression. The CR‐induced improvement in insulin sensitivity is associated with robust increases in IRS‐1 expression in both skeletal muscle and WAT.NIH AG006537, AG015897, AG029337, AG000279, The Swedish Medical Research Council
Influences of pregnancy on the core temperature response to ip TNF[alpha] in rats
Authors: Fewell James Edwin , Liu‐Tertil Limin 
Published: June 2021

Pregnant (P) rats exhibit hypothermia in response to doses of E. coli LPS that elicit fever in nonpregnant (NP) rats. In NP rats, LPS elicits significant increases in plasma concentrations of IL‐1β, IL‐6, IL‐1ra and TNFα whereas in P rats, LPS elicits significant increases in antipyretic/cryogenic cytokines (i.e., IL‐1ra & TNFα) but not in pyrogenic cytokines (i.e., IL‐1β & IL‐6). The present experiments were carried out on 58 NP and 56 near‐term P chronically‐instrumented and conscious rats to investigate the influence of pregnancy on the core temperature (Tc) responses to i.p. TNFa.In NP rats, doses of TNFa ranging from 0.1 to 1000 µg/kg produced significant increases in Tc (i.e., fever). In P rats, however, TNFa did not elicit fever but produced hypothermia in doses of 10µg/kg and greater. Thus, our data provide insight into the possible role that TNFα plays in mediating the differential Tc response to LPS in NP and P rats.
Soluble Guanylyl Cyclase and Cutaneous Active Vasodilation During Heat Stress in Humans
Authors: Kellogg Dean Lundt , Zhao Joan Liu , Wu Yubo Beth , Zhao Kun , Johnson John Marshall 
Published: June 2021

Nitric oxide(NO) dependent systems typically involve cGMP generation via NO activation of soluble guanylyl cyclase(sGC) as a step in vasodilation. We hypothesized this mechanism participates in cutaneous active vasodilation(AVD) during whole body heat stress(HS). We examined effects of a specific sGC inhibitor, ODQ, on AVD during HS. 3 intradermal microdialysis probes(MD) were inserted into forearm skin in 7 subjects. Skin blood flow was monitored by Laser‐Doppler Flowmetry(LDF). Body temperature was controlled with water‐perfused suits. Blood pressure was monitored by Finapres and cutaneous vascular conductance calculated(CVC=LDF/MAP). The study began with perfusion of Ringer's at all sites, followed by 2%DMSO in Ringer's or 1mM ODQ dissolved in 2%DMSO/Ringer's at 2 separate MD sites. (Preliminary studies showed that 1mMODQ antagonized NO mediated vasodilation by sodium nitroprusside.) Ringer's was continuously perfused at the 3rd control site(CTR). The protocol began with 40 minutes of normothermia followed by 3 minutes of cold stress(CS) after which whole body heating was performed to effect HS and activate AVD. After HS, 58mM SNP was perfused through all MD sites to maximally vasodilate for data normalization.Resultsthere were no differences between sites during normothermia. No differences were found between sites in normothermia or CS. There was no significant difference between Ringer's and DMSO sites at the peak of HS on CVC. ODQ tended to attenuate the maximal CVC achieved at the peak of HS(p=0.0536 vs CTR and DMSO). Blockade sGC by ODQ tended to attenuate AVD during HS, these data suggest that sGC activation participates in AVD.
The mechanisms of ethanol‐induced contraction of tracheal smooth muscle
Authors: Jakupaj Muharrem , Sopi Ramadan B , Neziri Burim , Krasniqi Avdyl , Devaja Shqipe , Dreshaj Ismail A 
Published: June 2021

We have shown that ethanol induces contraction of pulmonary artery smooth muscle. Therefore, we hypothesized that ethanol induces contractile responses of tracheal smooth muscle and extra cellular Ca2+ plays an important role on these responses. In vitro force measurements were performed in tracheal smooth muscle strips obtained from adult ferrets (n=33). TSM strips were treated with different concentration of ethanol (46 ‐ 322 mM). In another set of experiments strips were incubated in Ca2+ free Krebs ‐Hensleit solution or a Ca2+ channel blocker ‐ nifedipine was used and then treated with ethanol. The involvement of nitric oxide (NO) was studied by inhibition of nitric oxide synthase (NOS) using Nω‐nitro‐L‐arginine methyl ester. The ethanol induced concentration‐dependent contraction of TSM. Prior treatment of tissues with a single dose of ethanol increased the contractile responses of TSM to acetylcholine (p<0.05). Lack of Ca2+ in medium resulted with decrease of contractile force of the TSM likewise Ca2+ channel blocker. Inhibition of NOS significantly increased contractile responses (p<0.001).These data demonstrate that ethanol induces contraction of TSM and it appears to play a critical role in enhancing cholinergically mediated contractile responses of TSM. Extra cellular Ca2+ plays an important role on these responses and NO release as a relaxant molecule counteracts the effects of ethanol on TSM.