bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the PPAR-γ2 Pro12Ala Polymorphism and ACE Inhibitor Therapy on New-Onset Microalbuminuria in Type 2 Diabetes: Evidence From BENEDICT
Authors: De Cosmo Salvatore , Motterlini Nicola , Prudente Sabrina , Pellegrini Fabio , Trevisan Roberto , Bossi Antonio , Remuzzi Giuseppe , Trischitta Vincenzo , Ruggenenti Piero ,   on behalf of the BENEDICT Study Group
Published: September 2009

OBJECTIVE
Cross-sectional studies found less microalbuminuria in type 2 diabetic patients with the Ala12 allele of the peroxisome proliferator–activated receptor-γ2 (PPAR-γ2) Pro12Ala polymorphism. We prospectively evaluated the association between Pro12Ala polymorphism (rs1801282) and new-onset microalbuminuria.

RESEARCH DESIGN AND METHODS
Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1,119 consenting patients from BErgamo NEphrologic DIabetic Complications Trial (BENEDICT)—a prospective, randomized trial evaluating ACE inhibition effect on new-onset microalbuminuria (albuminuria 20–200 μg/min in at least two of three consecutive overnight urine collections in two consecutive visits) in hypertensive type 2 diabetes with albuminuria &lt;20 μg/min at inclusion.

RESULTS
Baseline characteristics of Ala (Ala/Ala or Ala/Pro) carriers and Pro/Pro homozygotes were similar, with a nonsignificant trend to lower albuminuria (P = 0.1107) in the 177 Ala carriers. Over a median (interquartile range) of 44.0 (17.1–51.9) months, 7 (4%) Ala carriers and 86 (9.1%) Pro/Pro homozygotes developed microalbuminuria (hazard ratio [HR] 0.45 [95% CI 0.21–0.97]; P = 0.042). Final albuminuria was significantly lower in Ala carriers than Pro/Pro homozygotes (7.3 ± 9.1 vs. 10.5 ± 24.9 μg/min, respectively), even after adjustment for baseline albuminuria (P = 0.048). Baseline and follow-up blood pressure and metabolic control were similar in both groups. Incidence of microalbuminuria was significantly decreased by ACE versus non-ACE inhibitor therapy in Pro/Pro homozygotes (6.3 vs. 11.9%, respectively, HR 0.46 [0.29–0.72]; P &lt; 0.001).

CONCLUSIONS
In type 2 diabetes, the Ala allele protects from worsening albuminuria and new-onset microalbuminuria, and ACE inhibition blunts the excess risk of microalbuminuria associated with the Pro/Pro genotype. Evaluating Pro12Ala polymorphism may help identifying patients at risk who may benefit the most from early renoprotective therapy.
Fibroblast Growth Factor-21 Is Induced in Human Skeletal Muscles by Hyperinsulinemia
Authors: Hojman Pernille , Pedersen Maria , Nielsen Anders Rinnov , Krogh-Madsen Rikke , Yfanti Christina , Åkerstrom Thorbjørn , Nielsen Søren , Pedersen Bente Klarlund 
Published: September 2009

OBJECTIVE
Fibroblast growth factor-21 (FGF-21) is a potent metabolic regulator, which in animal models has been shown to improve glucose metabolism and insulin sensitivity. Recently, FGF-21 was shown to be expressed and secreted from murine muscle cells in response to insulin stimulation.

RESEARCH DESIGN AND METHODS
We studied muscular FGF-21 expression and plasma FGF-21 after acute insulin stimulation in young healthy men during a hyperinsulinemic- euglycemic clamp. Furthermore, we investigated systemic levels and muscle FGF-21 expression in humans with or without insulin resistance and chronic elevated insulin.

RESULTS
FGF-21 was barely detectable in young healthy men before insulin infusion. After 3 or 4 h of insulin infusion during a hyperinsulinemic-euglycemic clamp, muscular FGF-21 expression increased significantly. Plasma FGF-21 followed the same pattern. In individuals with chronic elevated insulin, muscular FGF-21 expression was associated with hyperinsulinemia in men but not in women. In plasma, hyperinsulinemia and fasting glucose were positively associated with plasma FGF-21 while plasma FGF-21 correlated negatively with HDL cholesterol. No associations between muscle and plasma FGF-21 were found in the individuals with chronic hyperinsulinemia.

CONCLUSIONS
FGF-21 is expressed in human skeletal muscle in response to insulin stimulation, suggesting that FGF-21 is an insulin-regulated myokine. In support, we found an association between chronic hyperinsulinemia and levels of FGF-21.
Functional Role of Neuroendocrine-Specific Protein-Like 1 in Membrane Translocation of GLUT4
Authors: Ikemoto Takaaki , Hosoya Takamitsu , Takata Kumi , Aoyama Hiroshi , Hiramatsu Toshiyuki , Onoe Hirotaka , Suzuki Masaaki , Endo Makoto 
Published: September 2009

OBJECTIVE
In skeletal muscles, dantrolene inhibits the exercise-induced membrane translocation of GLUT4. It has been postulated that the inhibitory action of dantrolene on Ca2+ release from the sarcoplasmic reticulum (SR) causes inhibition of exercise-induced glucose uptake; however, the precise mechanism has not been adequately studied.

RESEARCH DESIGN AND METHODS
We discovered that dantrolene can bind to skeletal-type neuroendocrine-specific protein-like 1 (sk-NSPl1) with photoreactive dantrolene derivatives. In sk-NSPl1–deficient muscles, we examined the change in glucose uptake and the membrane translocation of GLUT4. In addition, we examined the change in blood glucose and also measured the glycogen level in both isolated and in situ skeletal muscles after electrical stimulation using our mutant mouse.

RESULTS
In sk-NSPl1–deficient muscles, exercise-induced glucose uptake was totally abolished with no change in insulin-induced glucose uptake. The Ca2+ release mechanism and its inhibition by dantrolene were completely preserved in these muscles. The expression of GLUT4 in the mutant muscles also appeared unchanged. Confocal imaging and results using the membrane isolation method showed that exercise/contraction did not enhance GLUT4 translocation in these sk-NSPl1–deficient muscles under conditions of adequate muscle glycogen consumption. The blood glucose level in normal mice was reduced by electrical stimulation of the hind limbs, but that in mutant mice was unchanged.

CONCLUSIONS
sk-NSPl1 is a novel dantrolene receptor that plays an important role in membrane translocation of GLUT4 induced by contraction/exercise. The 23-kDa sk-NSPl1 may also be involved in the regulation of glucose levels in the whole body.
Enhancement of Muscle Mitochondrial Oxidative Capacity and Alterations in Insulin Action Are Lipid Species Dependent
Authors: Turner Nigel , Hariharan Krit , TidAng Jennifer , Frangioudakis Georgia , Beale Susan M. , Wright Lauren E. , Zeng Xiao Yi , Leslie Simon J. , Li Jing-Ya , Kraegen Edward W. , Cooney Gregory J. , Ye Ji-Ming 
Published: September 2009

OBJECTIVE
Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action.

RESEARCH DESIGN AND METHODS
C57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4–5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured.

RESULTS
Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P &lt; 0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20–50%, P &lt; 0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet–fed controls; however; the increase in oxidative capacity was substantially greater in MCFA-fed animals (50–140% versus low-fat–fed controls, P &lt; 0.01). The MCFA diet induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic enzymes. In rats, isocaloric feeding of MCFA or LCFA high-fat diets induced hepatic insulin resistance to a similar degree; however, insulin action was preserved at the level of low-fat diet–fed controls in muscle and adipose from MCFA-fed animals.

CONCLUSIONS
MCFAs reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance in the liver. Dietary supplementation with MCFAs may therefore be beneficial for preventing obesity and peripheral insulin resistance.
Severe Insulin Resistance and Intrauterine Growth Deficiency Associated With Haploinsufficiency for INSR and CHN2
Authors: Suliman Sara G.I. , Stanik Juraj , McCulloch Laura J. , Wilson Natalie , Edghill Emma L. , Misovicova Nadezda , Gasperikova Daniela , Sandrikova Vilja , Elliott Katherine S. , Barak Lubomir , Ellard Sian , Volpi Emanuela V. , Klimes Iwar , Gloyn Anna L. 
Published: September 2009

OBJECTIVE
Digenic causes of human disease are rarely reported. Insulin via its receptor, which is encoded by INSR, plays a key role in both metabolic and growth signaling pathways. Heterozygous INSR mutations are the most common cause of monogenic insulin resistance. However, growth retardation is only reported with homozygous or compound heterozygous mutations. We describe a novel translocation [t(7,19)(p15.2;p13.2)] cosegregating with insulin resistance and pre- and postnatal growth deficiency. Chromosome translocations present a unique opportunity to identify modifying loci; therefore, our objective was to determine the mutational mechanism resulting in this complex phenotype.

RESEARCH DESIGN AND METHODS
Breakpoint mapping was performed by fluorescence in situ hybridization (FISH) on patient chromosomes. Sequencing and gene expression studies of disrupted and adjacent genes were performed on patient-derived tissues.

RESULTS
Affected individuals had increased insulin, C-peptide, insulin–to–C-peptide ratio, and adiponectin levels consistent with an insulin receptoropathy. FISH mapping established that the translocation breakpoints disrupt INSR on chromosome 19p15.2 and CHN2 on chromosome 7p13.2. Sequencing demonstrated INSR haploinsufficiency accounting for elevated insulin levels and dysglycemia. CHN2 encoding β-2 chimerin was shown to be expressed in insulin-sensitive tissues, and its disruption was shown to result in decreased gene expression in patient-derived adipose tissue.

CONCLUSIONS
We present a likely digenic cause of insulin resistance and growth deficiency resulting from the combined heterozygous disruption of INSR and CHN2, implicating CHN2 for the first time as a key element of proximal insulin signaling in vivo.
Prenatal Programming of Metabolic Syndrome in the Common Marmoset Is Associated With Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1
Authors: Nyirenda Moffat J. , Carter Roderick , Tang Justin I. , de Vries Annick , Schlumbohm Christina , Hillier Stephen G. , Streit Frank , Oellerich Michael , Armstrong Victor W. , Fuchs Eberhard , Seckl Jonathan R. 
Published: September 2009

OBJECTIVE
Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which amplifies local tissue glucocorticoid concentrations. The reasons for this 11β-HSD1 dysregulation are unknown. Here, we tested whether 11β-HSD1 expression, like the metabolic syndrome, is “programmed” by prenatal environmental events in a nonhuman primate model, the common marmoset monkey.

RESEARCH DESIGN AND METHODS
We used a “fetal programming” paradigm where brief antenatal exposure to glucocorticoids leads to the metabolic syndrome in the offspring. Pregnant marmosets were given the synthetic glucocorticoid dexamethasone orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11β-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age.

RESULTS
Prenatal dexamethasone administration, selectively during late gestation, resulted in early and persistent elevations in 11β-HSD1 mRNA expression and activity in the liver, pancreas, and subcutaneous—but not visceral—fat. The increase in 11β-HSD1 occurred before animals developed obesity or overt features of the metabolic syndrome. In contrast to rodents, in utero dexamethasone exposure did not alter glucocorticoid receptor expression in metabolic tissues in marmosets.

CONCLUSIONS
These data suggest that long-term upregulation of 11β-HSD1 in metabolically active tissues may follow prenatal “stress” hormone exposure and indicates a novel mechanism for fetal origins of adult obesity and the metabolic syndrome.
Use of Multiple Metabolic and Genetic Markers to Improve the Prediction of Type 2 Diabetes: the EPIC-Potsdam Study
Authors: Schulze Matthias B. , Weikert Cornelia , Pischon Tobias , Bergmann Manuela M. , Al-Hasani Hadi , Schleicher Erwin , Fritsche Andreas , Häring Hans-Ulrich , Boeing Heiner , Joost Hans-Georg 
Published: September 2009

OBJECTIVE
We investigated whether metabolic biomarkers and single nucleotide polymorphisms (SNPs) improve diabetes prediction beyond age, anthropometry, and lifestyle risk factors.

RESEARCH DESIGN AND METHODS
A case-cohort study within a prospective study was designed. We randomly selected a subcohort (n = 2,500) from 26,444 participants, of whom 1,962 were diabetes free at baseline. Of the 801 incident type 2 diabetes cases identified in the cohort during 7 years of follow-up, 579 remained for analyses after exclusions. Prediction models were compared by receiver operatoring characteristic (ROC) curve and integrated discrimination improvement.

RESULTS
Case-control discrimination by the lifestyle characteristics (ROC-AUC: 0.8465) improved with plasma glucose (ROC-AUC: 0.8672, P &lt; 0.001) and A1C (ROC-AUC: 0.8859, P &lt; 0.001). ROC-AUC further improved with HDL cholesterol, triglycerides, γ-glutamyltransferase, and alanine aminotransferase (0.9000, P = 0.002). Twenty SNPs did not improve discrimination beyond these characteristics (P = 0.69).

CONCLUSIONS
Metabolic markers, but not genotyping for 20 diabetogenic SNPs, improve discrimination of incident type 2 diabetes beyond lifestyle risk factors.
Exploration of the Relationship Between Household Food Insecurity and Diabetes in Canada
Authors: Gucciardi Enza , Vogt Janet A. , DeMelo Margaret , Stewart Donna E. 
Published: September 2009

OBJECTIVE
To determine the household food insecurity (HFI) prevalence in Canadians with diabetes and its relationship with diabetes management, self-care practices, and health status.

RESEARCH DESIGN AND METHODS
We analyzed data from Canadians with diabetes aged ≥12 years (n = 6,237) from cycle 3.1 of the Canadian Community Health Survey, a population-based cross-sectional survey conducted in 2005. The HFI prevalence in Canadians with diabetes was compared with that in those without diabetes. The relationships between HFI and management services, self-care practices, and health status were examined for Ontarians with diabetes (n = 2,523).

RESULTS
HFI was more prevalent among individuals with diabetes (9.3% [8.2–10.4]) than among those without diabetes (6.8% [6.5–7.0]) and was not associated with diabetes management services but was associated with physical inactivity (odds ratio 1.54 [95% CI 1.10–2.17]), lower fruit and vegetable consumption (0.52 [0.33–0.81]), current smoking (1.71 [1.09–2.69]), unmet health care needs (2.71 [1.74–4.23]), having been an overnight patient (2.08 [1.43–3.04]), having a mood disorder (2.18 [1.54–3.08]), having effects from a stroke (2.39 [1.32–4.32]), lower satisfaction with life (0.28 [0.18–0.43]), self-rated general (0.37 [0.21–0.66]) and mental (0.17 [0.10–0.29]) health, and higher self-perceived stress (2.04 [1.30–3.20]). The odds of HFI were higher for an individual in whom diabetes was diagnosed at age &lt;40 years (3.08 [1.96–4.84]).

CONCLUSIONS
HFI prevalence is higher among Canadians with diabetes and is associated with an increased likelihood of unhealthy behaviors, psychological distress, and poorer physical health.
Test Methods for Hyperelastic Characterization of Rubber
Authors: Kupchella R. , Kidney J. , Hutchison W. 
Published: September 2009

Abstract
Optical methods using digital image correlation (DIC) are utilized in developing rubber constitutive tests. Two and three dimensional DIC systems are employed to measure strains on rubber specimens subjected to uniaxial, planar, and biaxial stress states. A special membrane inflation test was developed and is described for providing the biaxial constitutive data. Deformation-induced material property changes for the three modes of testing are quantified using a concept based on energy dissipation. The constitutive test strain ranges for each of the three modes are separately selected to equalize the material states. The methodology is applied to filled rubber compounds in order to characterize them in terms of hyperelastic behavior. Evaluation and comparison of several common hyperelastic models are given, and application to finite element modeling of a structural rubber specimen is described.
Effects of opioid receptor activation on thermal antinociception in red-eared slider turtles (Trachemys scripta)
Authors: Sladky Kurt K. , Kinney Matthew E. , Johnson Stephen M. 
Published: September 2009

Abstract
Objective—To determine the effects of μ-, δ-, and κ-opioid receptor (MOR, DOR, and KOR, respectively) activation on thermal antinociception in red-eared slider turtles Trachemys scripta.
Animals—51 adult turtles.
Procedures—Infrared heat stimuli were applied to the plantar surface of turtle hind limbs. Thermal hind limb withdrawal latencies (HLWLs) were measured before (baseline) and at intervals after SC administration of various doses of saline (0.9% NaCl) solution (SS), MOR, DOR, or KOR agonists (3 to 13 turtles/treatment). Treatment with a DOR antagonist SC prior to DOR agonist administration was also evaluated.
Results—Treatment with an MOR agonist ([D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin acetate salt [DAMGO; 1.3 or 6.6 mg/kg]) increased HLWLs (from baseline) at 2 to 8 hours after injection; at the higher dose, the maximum mean increase was 5.6 seconds at 4 hours. Treatment with a DOR agonist ([D-Ala2, D-Leu5]-enkephalin acetate salt [DADLE; 25 mg/kg]) increased mean HLWL by 11.3 seconds at 4 hours; however, treatment with DADLE (5.8 mg/kg) or with another DOR agonist ([D-Pen2,5]-enkephalin hydrate [DPDPE; 1.2 or 6.3 mg/kg]) did not alter HLWL, compared with SS effects. Administration of a DOR antagonist (naltrindole hydrochloride; 10 mg/kg) prior to DADLE administration (25 mg/kg) increased mean HLWL by 2.7 seconds at 4 hours. One KOR agonist, U50488 ([−]-trans-[1S,2S]-U50488 hydrochloride hydrate; 6.7 mg/kg) decreased HLWL steadily from 2 to 24 hours (less than baseline value); another KOR agonist, U69593 ([+]-[5α,7α,8β]-N-Methyl-N-[7-{1-pyrrolidinyl}-1-oxaspiro{4.5}dec-8-yl]-benzene-acet-amide; 6.7 or 26 mg/kg) did not alter HLWLs, compared with SS effects.
Conclusions and Clinical Relevance—Opioid-dependent thermal antinociception in turtles appeared to be attributable mainly to MOR activation with a relatively minor contribution of DOR activation.
Characterization of eversion syndrome in captive Scyphomedusa jellyfish
Authors: Freeman Kate S. , Lewbart Gregory A. , Robarge Wayne P. , Harms Craig A. , Law J. Mchugh , Stoskopf Michael K. 
Published: September 2009

Abstract
Objective—To determine whether Scyphomedusa jellyfish with eversion syndrome had alterations in husbandry conditions, elemental content, or histologic appearance, compared with unaffected jellyfish.
Animals—123 jellyfish (44 with eversion syndrome and 79 without) at 6 institutions.
Procedures—Elemental analyses were performed on 24 jellyfish with eversion syndrome and 49 without, and histologic examinations were performed on 20 jellyfish with eversion syndrome and 30 without. A questionnaire distributed to 39 institutions with Scyphomedusa jellyfish was used to gather information about husbandry, environmental conditions, and prevalence of eversion syndrome.
Results—For the 39 institutions that responded to the questionnaire, prevalence of eversion syndrome ranged from 0% to 30%. For Aurelia aurita, eversion was more common at institutions with only captive-raised and no wild-caught jellyfish. Eversion was most common among young (approx 1- to 2-month-old) growing jellyfish and older (> 6-month-old) jellyfish. Elemental analysis revealed only minor differences between affected and unaffected jellyfish, with great variation among jellyfish from the same institution and among jellyfish from different institutions. Striated muscle degeneration and necrosis and extracellular matrix (mesoglea) degeneration were evident on histologic examination of affected jellyfish.
Conclusions and Clinical Relevance—Results suggested that eversion syndrome is a complex phenomenon associated with degenerative changes of the bell matrix.
Use of a polymerase chain reaction assay to study response to oxytetracycline treatment in experimental Candidatus Mycoplasma haemolamae infection in alpacas
Authors: Tornquist Susan J. , Boeder Lisa J. , Cebra Christopher K. , Messick Joanne 
Published: September 2009

Abstract
Objective—To develop a PCR assay for Candidatus Mycoplasma haemolamae (CMhl) infection in alpacas and use it to study the efficacy of oxytetracycline treatment and development of a subclinical carrier state.
Animals—8 healthy adult alpacas.
Procedures—Alpacas initially had negative results for CMhl in blood samples via PCR assay and were experimentally infected with CMhl; 4 were treated with oxytetracycline, and 4 were not treated. All were monitored regularly via PCR assay, blood smear examination, PCV, rectal temperature, and physical examination. At 6 months after treatment, all alpacas were immunosuppressed by administration of dexamethasone and tested for CMhl.
Results—7 of 8 alpacas had positive PCR assay results 4 to 6 days after experimental infection. When organisms were detectable on a blood smear, they were seen 2 to 6 days after positive results of PCR assay. Infection was often associated with mild anemia that was usually transient. No alpacas became hypoglycemic. Oxytetracycline treatment was not associated with faster clearance of organisms or resolution of anemia, and 4 of 4 treated alpacas still had positive results of PCR assay when immunosuppressed 6 months later; 0 of 3 nontreated alpacas had positive results of PCR assay following immunosuppression. Transient fever was detected in 3 alpacas during immunosuppression.
Conclusions and Clinical Relevance—The PCR assay was more sensitive than blood smear examination for detection of infection. Clinical signs, anemia, and fever were not necessarily associated with infection. Oxytetracyline administration did not consistently clear CMhl infection. Although treated with oxytetracycline, infected alpacas remained chronic carriers.