bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Action in the Double Incretin Receptor Knockout Mouse
Authors: Ayala Julio E. , Bracy Deanna P. , Hansotia Tanya , Flock Grace , Seino Yutaka , Wasserman David H. , Drucker Daniel J. 
Published: November 2007

OBJECTIVE—The incretins glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide have been postulated to play a role in regulating insulin action, although the mechanisms behind this relationship remain obscure. We used the hyperinsulinemic-euglycemic clamp to determine sites where insulin action may be modulated in double incretin receptor knockout (DIRKO) mice, which lack endogenous incretin action.
RESEARCH DESIGN AND METHODS—DIRKO and wild-type mice were fed regular chow or high-fat diet for 4 months. Clamps were performed on 5-h–fasted, conscious, unrestrained mice using an arterial catheter for sampling.
RESULTS—Compared with wild-type mice, chow and high fat–fed DIRKO mice exhibited decreased fat and muscle mass associated with increased energy expenditure and ambulatory activity. Clamp rates of glucose infusion (GIR), endogenous glucose production (endoRa), and disappearance (Rd) were not different in chow-fed wild-type and DIRKO mice, although insulin levels were lower in DIRKO mice. Liver Akt expression was decreased but Akt activation was increased in chow-fed DIRKO compared with wild-type mice. High-fat feeding resulted in fasting hyperinsulinemia and hyperglycemia in wild-type but not in DIRKO mice. GIR, suppression of endoRa, and stimulation of Rd were inhibited in high fat–fed wild-type mice but not in DIRKO mice. High-fat feeding resulted in impaired tissue glucose uptake (Rg) in skeletal muscle of wild-type mice but not of DIRKO mice. Liver and muscle Akt activation was enhanced in high fat–fed DIRKO compared with wild-type mice.
CONCLUSIONS—In summary, DIRKO mice exhibit enhanced insulin action compared with wild-type mice when fed a regular chow diet and are protected from high-fat diet–induced obesity and insulin resistance.
Key Role for AMP-Activated Protein Kinase in the Ventromedial Hypothalamus in Regulating Counterregulatory Hormone Responses to Acute Hypoglycemia
Authors: McCrimmon Rory J. , Shaw Margaret , Fan Xiaoning , Cheng Haiying , Ding Yuyan , Vella Monica C. , Zhou Ligang , McNay Ewan C. , Sherwin Robert S. 
Published: November 2007

OBJECTIVE—To examine in vivo in a rodent model the potential role of AMP-activated protein kinase (AMPK) within the ventromedial hypothalamus (VMH) in glucose sensing during hypoglycemia.
RESEARCH DESIGN AND METHODS—Using gene silencing technology to selectively downregulate AMPK in the VMH, a key hypothalamic glucose-sensing region, we demonstrate a key role for AMPK in the detection of hypoglycemia. In vivo hyperinsulinemic-hypoglycemic (50 mg dl−1) clamp studies were performed in awake, chronically catheterized Sprague-Dawley rats that had been microinjected bilaterally to the VMH with an adeno-associated viral (AAV) vector expressing a short hairpin RNA for AMPKα.
RESULTS—In comparison with control studies, VMH AMPK downregulation resulted in suppressed glucagon (∼60%) and epinephrine (∼40%) responses to acute hypoglycemia. Rats with VMH AMPK downregulation also required more exogenous glucose to maintain the hypoglycemia plateau and showed significant reductions in endogenous glucose production and whole-body glucose uptake.
CONCLUSIONS—We conclude that AMPK in the VMH plays a key role in the detection of acute hypoglycemia and initiation of the glucose counterregulatory response.
Fas-Associated Death Receptor Signaling Evoked by Human Amylin in Islet β-Cells
Authors: Zhang Shaoping , Liu Hong , Yu Hua , Cooper Garth J.S. 
Published: November 2007

OBJECTIVE— Aggregation of human amylin (hA) into β-sheet–containing oligomers is linked to islet β-cell dysfunction and the pathogenesis of type 2 diabetes. Here, we investigated possible contributions of Fas-associated death-receptor signaling to the mechanism of hA-evoked β-cell apoptosis.
RESEARCH DESIGN AND METHODS— We measured responses to hA in isolated mouse islets and two insulinoma cell lines, wherein we measured Fas/Fas ligand (FasL) and Fas-associated death domain (FADD) expression by quantitative RT-PCR, Western blotting, and immunofluorescence staining. We used two anti-Fas/FasL blocking antibodies and the Fas/FasL antagonist Kp7–6 to probe roles of Fas interactions in the regulation of apoptosis in hA-treated β-cells and measured Kp7–6–mediated effects on β-sheet formation and aggregation using circular dichroism and thioflavin-T binding.
RESULTS— hA treatment stimulated Fas and FADD expression in β-cells. Both blocking antibodies suppressed hA-evoked apoptosis but did not modify its aggregation. Therefore, Fas receptor interactions played a critical role in induction of this pathway. Interestingly, hA-evoked β-cell apoptosis was suppressed and rescued by Kp7–6, which also impaired hA β-sheet formation.
CONCLUSIONS— This is the first report linking hA-evoked induction and activation of Fas and FADD to β-cell apoptosis. We have identified a Fas/FasL antagonist, Kp7–6, as a potent inhibitor of hA aggregation and related β-cell death. These results also support an interaction between hA and Fas on the surface of apoptotic β-cells. Increased expression and activation of Fas in β-cells could constitute a molecular event common to the pathogenesis of both type 1 and type 2 diabetes, although the mode of pathway activation may differ between these common forms of diabetes.
High Visceral and Low Abdominal Subcutaneous Fat Stores in the Obese Adolescent
Authors: Taksali Sara E. , Caprio Sonia , Dziura James , Dufour Sylvie , Calí Anna M.G. , Goodman T. Robin , Papademetris Xenophon , Burgert Tania S. , Pierpont Bridget M. , Savoye Mary , Shaw Melissa , Seyal Aisha A. , Weiss Ram 
Published: November 2007

OBJECTIVE— To explore whether an imbalance between the visceral and subcutaneous fat depots and a corresponding dysregulation of the adipokine milieu is associated with excessive accumulation of fat in the liver and muscle and ultimately with insulin resistance and the metabolic syndrome.
RESEARCH DESIGN AND METHODS— We stratified our multi-ethnic cohort of 118 obese adolescents into tertiles based on the proportion of abdominal fat in the visceral depot. Abdominal and liver fat were measured by magnetic resonance imaging and muscle lipid (intramyocellular lipid) by proton magnetic resonance spectroscopy.
RESULTS— There were no differences in age, BMI Z score, or fat-free mass across tertiles. However, as the proportion of visceral fat increased across tertiles, BMI and percentage of fat and subcutaneous fat decreased, while hepatic fat increased. In addition, there was an increase in 2-h glucose, insulin, c-peptide, triglyceride levels, and insulin resistance. Notably, both leptin and total adiponectin were significantly lower in tertile 3 than 1, while C-reactive protein and interleukin-6 were not different across tertiles. There was a significant increase in the odds ratio for the metabolic syndrome, with subjects in tertile 3 5.2 times more likely to have the metabolic syndrome than those in tertile 1.
CONCLUSIONS— Obese adolescents with a high proportion of visceral fat and relatively low abdominal subcutaneous fat have a phenotype reminiscent of partial lipodystrophy. These adolescents are not necessarily the most severely obese, yet they suffer from severe metabolic complications and are at a high risk of having the metabolic syndrome.
Insulin Signaling Stimulates Insulin Transport by Bovine Aortic Endothelial Cells
Authors: Wang Hong , Wang Aileen X. , Liu Zhenqi , Barrett Eugene J. 
Published: November 2007

OBJECTIVE—In vivo evidence suggests that insulin entry into skeletal muscle is rate limiting for its overall metabolic action. Although there has been controversy regarding whether insulin crosses the endothelium by a passive (transcellular or paracellular) or mediated process, accumulating data favor the latter. Here, we addressed whether insulin signaling within the endothelial cell is required for the first step of transendothelial insulin transport: its uptake by the endothelial cell.
RESEARCH DESIGN AND METHODS—Bovine aortic endothelial cells (bAECs) were incubated in serum-free medium for 6 h before addition of 50 nmol/l fluoroisothiocyanate (FITC)-labeled insulin for 30 min, and uptake of FITC insulin was quantified by confocal immunocytochemistry.
RESULTS—Cellular insulin uptake was temperature dependent, being greater at 37 vs. 4°C (P &lt; 0.05). Inhibiting phosphatidylinositol 3-kinase (PI 3-kinase) (wortmannin), mitogen-activated protein kinase kinase (MEK) (PD98059), the cSrc-family tyrosine kinase (PP1), or the insulin receptor tyrosine kinase (genistein) markedly diminished FITC insulin uptake (P &lt; 0.05 for each). In contrast, inhibiting the phosphotyrosine phosphatase protein tyrosine phosphatase 1B further stimulated insulin uptake (P &lt; 0.05). Addition of the inflammatory cytokine 5 ng/ml tumor necrosis factor-α (TNF-α) for 6 h before adding 50 nmol/l FITC insulin diminished insulin uptake significantly (P &lt; 0.05). This inhibitory effect of TNF-α could be partially reversed by a specific p38 MAPK inhibitor (SB203580).
CONCLUSIONS—Insulin uptake by bAECs requires intact insulin signaling via both the PI 3-kinase and MEK signaling cascades and the cSrc-family tyrosine kinases, and endothelial cell insulin uptake is sensitive to cytokine-induced insulin resistance.
Increased Glucose Levels Are Associated With Episodic Memory in Nondiabetic Women
Authors: Rolandsson Olov , Backeström Anna , Eriksson Sture , Hallmans Göran , Nilsson Lars-Göran 
Published: November 2007

OBJECTIVE—Patients with type 2 diabetes have an increased risk of a reduction in cognitive function. We investigated the hypothesis that plasma glucose is associated with a reduction in episodic and/or semantic memory already in nondiabetic subjects.
RESEARCH DESIGN AND METHODS—We linked two large population-based datasets in Sweden: the Betula study, in which a random sample from the population aged 35–85 years was investigated for cognitive function, including episodic and semantic memory; and the Västerbotten Intervention Program, a health survey with subjects aged 40, 50, and 60 years, that includes measuring of fasting and 2-h plasma glucose, along with other risk factors for diabetes and cardiovascular disease. We identified 411 (179 men and 232 women, mean age 50.6 ± 8.0 years) nondiabetic subjects, free from dementia, who had participated in the two surveys within 6 months.
RESULTS—Women had better episodic (score 7.37 ± 1.42) and semantic memory (score 16.05 ± 2.76) than men (score 6.59 ± 1.29 and 15.15 ± 2.92, respectively, P &lt; 0.001 for both). In an adjusted multivariate model, fasting plasma glucose (fPG) and 2-h plasma glucose (2hPG) were significantly negatively associated with episodic memory (fPG: B −0.198, SE 0.068, β −0.209, P = 0.004; and 2hPG: B −0.061, SE 0.031, β −0.148, P = 0.048, respectively) in women but not in men. The association was not found in relation to semantic memory.
CONCLUSIONS—We conclude that an increase in plasma glucose is associated with impairment in episodic memory in women. This could be explained by a negative effect on the hippocampus caused by raised plasma glucose levels.
Effect of transportation stress on heat shock protein 70 concentration and mRNA expression in heart and kidney tissues and serum enzyme activities and hormone concentrations of pigs
Authors: Yu Hong , Bao En-dong , Zhao Ru-qian , Lv Qiong-xia 
Published: November 2007

Abstract
Objective—To determine the enzymatic and hormonal responses, heat shock protein 70 (Hsp70) production, and Hsp70 mRNA expression in heart and kidney tissues of transport-stressed pigs.
Animals—24 pigs (mean weight, 20 ± 1 kg).
Procedures—Pigs were randomly placed into groups of 12 each. One group was transported for 2 hours. The other group was kept under normal conditions and used as control pigs. Sera were used to detect triiodothyronine, thyroxine, and cortisol concentrations and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities. The heart and kidneys of anesthetized pigs were harvested and frozen in liquid nitrogen for quantification of Hsp70 and Hsp70 mRNA.
Results—No significant differences were detected in serum alanine aminotransferase activity and triiodothyronine and cortisol concentrations between groups; however, the serum creatine kinase and aspartate aminotransferase activities and thyroxine concentrations were higher in transported pigs. Densitometric readings of western blots revealed that the amount of Hsp70 in heart and kidney tissues was significantly higher in transported pigs, compared with control pigs. Results of fluorescence quantitative real-time PCR assay revealed that the Hsp70 mRNA transcription in heart tissue, but not kidney tissue, was significantly higher in transported pigs, compared with control pigs.
Conclusions and Clinical Relevance—Transportation imposed a severe stress on pigs that was manifested as increased serum activities of aspartate aminotransferase and creatine kinase and increased amounts of Hsp70 and Hsp70 mRNA expression in heart and kidney tissues. Changes in serum enzyme activities were related to the tissue damage of transport-stressed pigs.
Comparison of insertion characteristics of two types of hydroxyapatite-coated and uncoated positive profile transfixation pins in the third metacarpal bone of horses
Authors: Zacharias Josh R. , Lescun Timothy B. , Moore George E. , Van Sickle David C. 
Published: November 2007

Abstract
Objective—To determine the effect of 2 hydroxyapatite pin coatings on heat generated at the bone-pin interface and torque required for insertion of transfixation pins into cadaveric equine third metacarpal bone.
Sample Population—Third metacarpal bone pairs from 27 cadavers of adult horses.
Procedures—Peak temperature of the bone at the cis-cortex and the hardware and pin at the trans-cortex was measured during insertion of a plasma-sprayed hydroxyapatite (PSHA)—coated, biomimetic hydroxyapatite (BMHA)—coated, or uncoated large animal transfixation pin. End-insertional torque was measured for each pin. The bone-pin interface was examined grossly and histologically for damage to the bone and coating.
Results—The BMHA-coated transfixation pins had similar insertion characteristics to uncoated pins. The PSHA-coated pins had greater mean peak bone temperature at the cis-cortex and greater peak temperature at the trans-cortex (70.9 ± 6.4°C) than the uncoated pins (38.7 ± 8.4°C). The PSHA-coated pins required more insertional torque (10,380 ± 5,387.8 Nmm) than the BMHA-coated pins (5,123.3 ± 2,296.9 Nmm). Four of the PSHA-coated pins became immovable after full insertion, and 1 gross fracture occurred during insertion of this type of pin.
Conclusions and Clinical Relevance—The PSHA coating was not feasible for use without modification of presently available pin hardware. The BMHA-coated pins performed similarly to uncoated pins. Further testing is required in an in vivo model to determine the extent of osteointegration associated with the BMHA-coated pins in equine bone.
Effects of changes in loading conditions and heart rate on the myocardial performance index in cats
Authors: Hori Yasutomo , Uechi Masami , Indou Atsuko 
Published: November 2007

Abstract
Objective—To evaluate the effect of changes in hemodynamics on the myocardial performance index (MPI) in cats.
Animals—6 mixed-breed cats.
Procedures—Cats were anesthetized by administration of thiopental sodium; anesthesia was maintained by administration of isoflurane. Systolic arterial pressure and central venous pressure were measured by use of catheters, and heart rate was controlled by right atrial pacing. Afterload was increased by balloon occlusion of the descending aorta, and preload was increased by IV infusion of lactated Ringer's solution at a rate of 40 mL/kg/h. Echocardiography was performed for each condition.
Results—Atrial pacing significantly increased heart rate. The MPI did not change with heart rate. Arterial pressure and MPI increased significantly during aortic occlusion. The IV infusion increased fractional shortening but did not change the MPI. Multiple regression analysis revealed that the MPI was not affected by heart rate, systolic arterial pressure, central venous pressure, fractional shortening, or velocity of the E wave.
Conclusions and Clinical Relevance—The MPI can be used to assess cardiac function in healthy cats. The MPI is independent of heart rate and systolic arterial pressure but is sensitive to changes in afterload.
Assessment of exercise-induced alterations in neutrophil function in horses
Authors: Donovan Douglas C. , Jackson Christie A. , Colahan Patrick T. , Norton Natalie N. , Clapper Joan L. , Moore James N. , Hurley David J. 
Published: November 2007

Abstract
Objective—To evaluate the effects of a standardized exercise test to exhaustion in horses on leukocyte function ex vivo.
Animals—6 Thoroughbred geldings.
Procedures—Blood samples were obtained from each horse before exercise; at exhaustion (termed failure); and at 2, 6, 24, 48, and 72 hours after exercise to evaluate hematologic changes, rate of leukocyte apoptosis, and leukocyte production of reactive oxygen species (ROS) ex vivo. To assess leukocyte function, leukocyte ROS production in response to stimulation with lipopolysaccharide, peptidoglycan, zymosan, and phorbol myristate acetate was evaluated. Apoptosis was evaluated via assessment of caspase activity in leukocyte lysates.
Results—In response to lipopolysaccharide, production of ROS by leukocytes was significantly increased at 2 hours and remained increased (albeit not significantly) at 6 hours after exercise, compared with the preexercise value. In the absence of any stimulus, leukocyte ROS production was significantly increased at 6 and 24 hours after exercise. In contrast, ROS production in response to phorbol myristate acetate was significantly decreased at 6, 24, and 72 hours after exercise. Leukocyte ROS production induced by zymosan or peptidoglycan was not altered by exercise. Leukocytosis was evident for 24 hours after exercise, and neutrophilia was detected during the first 6 hours. A significant increase in the rate of leukocyte apoptosis was detected at failure and 72 hours after exercise.
Conclusions and Clinical Relevance—Results indicated that strenuous exercise undertaken by horses causes alterations in innate immune system functions, some of which persist for as long as 72 hours after exercise.
Early laminar events involving endothelial activation in horses with black walnut– induced laminitis
Authors: Loftus John P. , Black Samuel J. , Pettigrew Amanda , Abrahamsen Eric J. , Belknap James K. 
Published: November 2007

Abstract
Objective—To determine proinflammatory gene expression, endothelial adhesion molecule gene expression, and matrix metalloproteinase (MMP) concentrations in laminar specimens at 1.5 hours after administration of black walnut extract (BWE) and to compare these values with later time points.
Animals—25 horses.
Procedures—After nasogastric administration of BWE, anesthesia was induced at 1.5 hours in early time point (ETP) horses (n = 5), between 3 and 4 hours in developmental time point horses (5), and between 9 and 10 hours in acute onset of lameness time point horses (5). Anesthesia was induced at 3 and 10 hours after nasogastric administration of water in 2 groups of control horses (3-hour control group, n = 5; 10-hour control group, 5). Real-time quantitative PCR assay was performed on laminar specimens from control and ETP horses for cyclooxygenase (COX)-1, COX-2, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-8, IL-10, MMP-2, and MMP-9 gene expression; and on laminar specimens from all groups for endothelial adhesion molecules, intercellular adhesion molecule (ICAM)-1, and E-selectin gene expression. Leukocyte emigration was assessed via CD13 immunohistochemistry, and gelatinase accumulation was determined by gelatin zymography.
Results—Laminar concentrations of IL-1β, IL-6, IL-8, COX-2, ICAM-1, and E-selectin mRNA were significantly increased in ETP horses, compared with control horses. Concentrations of IL-1β, IL-8, ICAM-1, and E-selectin mRNA peaked at 1.5 hours. In ETP horses, leukocyte emigration was present in 3 of 5 horses and pro–MMP-9 was detected in 2 of 5 horses.
Conclusions and Clinical Relevance—Results indicated that endothelial activation and laminar inflammation are early events in laminitis; MMP accumulation likely is a downstream event.
Regional seroprevalence of bluetongue virus in cattle in Illinois and western Indiana
Authors: Boyer Tim C. , Ward Michael P. , Wallace Richard L. , Singer Randall S. 
Published: November 2007

Abstract
Objective—To estimate seroprevalence of bluetongue virus (BTV) and the geographic distribution of seropositive cattle herds in Illinois and western Indiana.
Sample Population—10,585 serum samples obtained from cattle in 60 herds during 3 transmission seasons (2000 through 2002).
Procedures—In a longitudinal study, serum samples were tested for BTV antibodies by use of a competitive ELISA. Four geographic zones were created by use of mean minimum January temperature. A multivariable mixed-effects logistic regression model with a random effect for herd was used to estimate seropositive risk for zone, age of cattle, herd type, and transmission season.
Results—Overall, BTV antibodies were detected in 156 (1.5%) samples. Estimated seroprevalence in 2000, 2001, and 2002 was 1.49%, 0.97%, and 2.18%, respectively. Risk of being seropositive for BTV was associated with geographic zone and age. Seroprevalence increased progressively from northern to southern zones, with no evidence of BTV infection in the northernmost zone. In the southernmost zone, annual seroprevalence ranged from 8.65% to 11.00%. Adult cattle were 2.35 times as likely as juvenile cattle to be seropositive.
Conclusions and Clinical Relevance—Overall seroprevalence was lower than has been reported for Illinois cattle. Bluetongue virus antibodies were distributed heterogeneously in this region. Only in the southernmost zone was seroprevalence consistently > 2%. Regionalization of BTV risk based on state borders does not account for such variability. Serologic data could be combined with landscape, climate, and vector data to develop predictive models of BTV risk within transitional regions of the United States.
Effect of exercise on development of capillary supply and oxidative capacity in skeletal muscle of horses
Authors: Rietbroek Nancy J. , Dingboom Elizabeth G. , Schuurman Simon O. , Hengeveld-van der Wiel Ellen , Eizema Karin , Everts Maria E. 
Published: November 2007

Abstract
Objective—To determine whether postnatal development of oxidative capacity and capillary supply of skeletal muscle is affected by various movement regimens in horses.
Animals—35 foals.
Procedures—Dutch Warmblood foals were allocated into 3 groups (box stall rest, box stall rest with training, and free pasture exercise). Training comprised an increasing number of gallop sprints from 1 week after birth to 22 weeks of age. From 22 to 48 weeks, the 3 groups were combined and allowed to exercise freely. Capillary supply (diffusion index [ie, area supplied by 1 capillary]), citrate synthase (CS) activity, and succinate dehydrogenase (SDH) activity were measured in biopsy specimens of deep gluteus medius muscle.
Results—During the first 22 weeks, diffusion index increased in all 3 groups (the training and pasture groups had a smaller increase, compared with the box stall rest group), total SDH activity increased in the training and pasture groups and decreased in the box stall rest group, and CS activity decreased in all groups. The effect of the various movement regimens on the diffusion index remained after the groups were combined.
Conclusions and Clinical Relevance—Withholding of exercise had a negative effect on the capillary supply (ie, diffusion index increased) that remained after box stall rest was discontinued and on oxidative capacity. Box stall rest with training prevented the negative effects and eventually had the same positive effect as pasture exercise.