bluuebunny/crossref_metadata_2025_split huggingface dataset:
1948-P: Secretion of the Short-Form Gastric Inhibitory Polypeptide in Nondiabetic and Diabetic Subjects
Authors: TAKEDA YASUTAKA , FUJITA YUKIHIRO , YANAGIMACHI TSUYOSHI , MARUYAMA NOBUHIRO , BESSHO RYOICHI , SAKAGAMI HIDEMITSU , HANEDA MASAKAZU , OTA TSUGUHITO 
Published: June 2019

We previously reported that the short-form gastric inhibitory polypeptide (GIP) 1-30 is released from islet alpha cells and promotes insulin secretion in a paracrine manner in vitro. However, the role played by GIP 1-30 in glucose metabolism in vivo remains unclear. We developed an enzyme-linked immunosorbent assay (ELISA) specific for GIP 1-30 and measured GIP 1-30 secretion in nondiabetic subjects (ND, n = 8) and patients with type 2 diabetes (T2D, n = 9). We developed a sandwich ELISA by combining a novel antibody to the GIP C-terminus with the N-terminal anti-GIP 1-42 antibody that is already available. We explored cross-reactivities with incretins and glucagon-related peptides. We next subjected ND and T2D subjects to the cookie meal test (CMT: carbohydrates 75 g, lipids 28.5 g, proteins 8.5 g) and measured GIP 1-30 blood levels. Absorbance increased in a dose-dependent manner on addition of the GIP 1-30 amide but not GIP 1-42, GLP-1, or glucagon. Post-CMT loading, GIP 1-30 concentrations increased in both ND and T2D subjects; however, in ND subjects, the increases were much lower than those of GIP 1-42 (GIP 1-30, before loading: 1.4 ± 0.5 pmol/L, after: 1.9 ± 0.6 pmol/L; GIP 1-42, before: 8.2 ± 0.1 pmol/L, after: 204.0 ± 35.2 pmol/L, P&lt;0.05). In T2D patients, the GIP 1-30 levels, as assessed by the areas under the curves, tended to be lower than those in ND patients. The DPP-4 inhibitor significantly increased both GIP 1-30 and GIP 1-42 secretion in T2D patients.
In conclusion, we developed a novel ELISA that is highly specific for GIP 1-30, the secretion of which was promoted by a mixed meal to a blood level lower than that of GIP 1-42. As is also true of the incretins, GIP 1-30 levels increased upon administration of DPP-4 inhibitor; GIP 1-30 secretion may differ between ND and T2D subjects.

Disclosure
Y. Takeda: None. Y. Fujita: None. T. Yanagimachi: None. N. Maruyama: Employee; Self; Immuno-Biological Laboratoties Co.,Ltd. R. Bessho: None. H. Sakagami: None. M. Haneda: None. T. Ota: None.

Funding
Japan Society for the Promotion of Science
1961-P: Identification of a Novel Brown/Beige Fat-Derived Adipokine
Authors: CHOI CHAN HEE J. , CRANE AUDREY A. , COHEN PAUL 
Published: June 2019

Fat cells or adipocytes play a central role in obesity, diabetes, and metabolic disease. White adipocytes store excess energy in the form of triglycerol, and brown adipocytes dissipate chemical energy into heat. In addition to these bioenergetics functions, adipocytes also have important endocrine functions. While several adipocyte-derived secreted factors, or adipokines, have been shown to have important physiological roles, bioinformatic analyses suggest that adipocytes may secrete more than 1,000 unique polypeptides. The vast majority of these gene products remain uncharacterized, representing a major opportunity for discovering new biology with translational potential. To that end, we have employed chemical and genetic tools to label and enrich circulating proteins in a cell-selective manner. Using bio-orthogonal non-canonical amino acid tagging (BONCAT) along with mass spectrometry we have characterized the secretome of white, brown, and beige adipocytes. We have identified more than 800 unique proteins, with approximately 300 showing fat cell type specific enrichment. Our studies have focused on a brown and beige fat specific protein encoded by a previously uncharacterized open reading frame (BAT-ORF). The mRNA encoding this protein is expressed in UCP1+thermogenic adipocytes, induced by cold and repressed by warm temperature, and upregulated following thiazolidinedione treatment. We have found that the BAT-ORF gene encodes two isoforms, only one of which is secreted. We have generated mice with genetic deletion of each isoform using CRISPR-Cas9. Preliminary data suggests these mice have decreased energy expenditure. Complete characterization of these mice is underway and data will be presented. We will also present a method using genetically engineered mouse models that allows us to specifically label and enrich secreted proteins in the blood in a cell-type specific fashion.

Disclosure
C.J. Choi: None. A.A. Crane: None. P. Cohen: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-17-ACE-17 to P.C.)
1987-P: Nampt Deletion Changes Metabolism in Adipose Tissue and Prevents Diet-Induced Obesity
Authors: OKABE KEISUKE , NAWAZ ALLAH , FUJISAKA SHIHO , YAGI KUNIMASA , KADO TOMONOBU , USUI ISAO , NAKAGAWA TAKASHI , TOBE KAZUYUKI 
Published: June 2019

Nampt is the rate-limiting enzyme in salvage pathway in which NAD is mainly synthesized in mammalian cells. NAD plays very important role in various biological processes, such as energy production, energy consumption, aging, cell death, and DNA damage repair as a coenzyme of redox reactions or as a substrate of Sirtuins or Poly (ADP-ribose) polymerases. Besides, Nampt is highly expressed in mature adipocyte and secreted into extracellular. The extracellular Nampt is known to regulate systemic metabolic state. In short, Nampt works as a metabolic sensor and NAD integrates systemic metabolism. Recently, metabolism is thought to be closely related to cell differentiation. However, how NAD metabolism affects to adipogenesis remains unknown. In this study, we generated the adipose tissue specific Nampt knock out mice, Adiponectin-Cre Nampt flox/flox (KO) and conducted targeted-metabolomic analysis to investigate the metabolic effect, employing liquid-chromatograph mass spectrometry and gas-chromatograph mass spectrometry. Interestingly, KO showed resistant against diet-induced obesity (DIO), fed high fat high sucrose diet. Body weight and both inguinal and epididymal fat mass were significantly reduced in KO compared to wild type control mice. On the other hand, we revealed that Nampt-mediated NAD synthesis was up-regulated during differentiation of 3T3-L1 preadipocytes and the inhibition of Nampt significantly suppressed the differentiation. Our metabolomic analysis and ChIP-qPCR assay showed NAD contributed to the differentiation through the metabolic reprogramming and the subsequent epigenetic alteration to activate the transcription of adipogenic genes. This result indicated Nampt-mediated NAD synthesis regulated differentiation of preadipocytes to mature adipocytes. Together, our data suggested that adipose tissue specific Nampt deletion resulted in the resistance against DIO and it could be partly attributed to the inhibited differentiation of preadipocytes.

Disclosure
K. Okabe: None. A. Nawaz: Research Support; Spouse/Partner; Astellas Pharma Inc., Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company. Research Support; Self; Japan Society for the Promotion of Science. Research Support; Spouse/Partner; Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Shionogi & Co., Ltd., Takeda Pharmaceutical Company Limited. S. Fujisaka: None. K. Yagi: None. T. Kado: None. I. Usui: None. T. Nakagawa: None. K. Tobe: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Japan Diabetes Society. Research Support; Self; Bristol-Myers Squibb Company.

Funding
Japan Society for the Promotion of Science
1998-P: Progressive Liver Dysfunction Resulted from a High-Fat, High-Fructose Diet in Fatzo Mice
Authors: WANG XIAOLI , YE WEIWEI , CHEN YANG , ZHANG XIAOYU , WANG YIXIN , XIAO YONG-FU 
Published: June 2019

The FATZO mouse is a polygenic model with an intact leptin system and was developed by cross breeding of C57BL6/J (C57) with AKR/J. FATZO mice have been used in many dysmetabolic studies. The epidemic health issue of nonalcoholic fatty liver disease (NAFLD, including NASH) is the organ dysmetabolic manifestation. This study was to investigate a high fat/fructose diet (HFFD) on liver function in FATZO mice. The body weights of FATZO (n=30) at age of 9 to 10 weeks were significantly heavier than those of age-matched C57 (n=19) mice (39±0.4g vs. 23±0.2g, p&lt;0.001). The serum glucose levels in FATZO were higher than those in C57 (212±5mg/dL vs. 131±7mg/dL). The body weights were gradually increased during 5-month feeding with HFFD or 5C08 (Figure 1). FATZO+HFFD mice significantly elevated serum AST, ALT and ALP, compared with FATZO+5C08, C57+HFFD and C57+5C08 mice. These elevations in FATZO+HFFD mice reached peak in 3-month feeding and then maintained at the high levels (Figure 1). Serum TC, HDL and LDL (except TG) were also significantly elevated in FATZO+HFFD mice. Interestingly, serum glucose and HbA1c levels were significantly reduced in FATZO+HFFD mice (from 216±7mg/dL and 6.2±0.1% at the baseline to 169±5mg/dL and 4.3±0.1% after 5-month feeding, respectively). Our data demonstrate that the HFFD progressively caused liver dysfunction in FATZO, but not C57. FATZO + the HFFD could thus be a very valuable model for NAFLD/NASH research.

Disclosure
X. Wang: None. W. Ye: None. Y. Chen: None. X. Zhang: None. Y. Wang: None. Y. Xiao: Employee; Self; Crown Bioscience Inc.
201-OR: ADA Presidents' Select Abstract: Shared Medical Appointments (SMA) Improve Psychosocial Outcomes in Adolescents with Type 1 Diabetes (T1D)
Authors: RAYMOND JENNIFER , REID MARK W. , BERGET CARI , CAIN CINDY L. , ANDERSON BARBARA , KLINGENSMITH GEORGEANNA J. 
Published: June 2019

Background: T1D care delivery via SMA is associated with increased attendance and satisfaction in adolescents, but the impact of the model on clinical and psychosocial outcomes remains unclear.
Objective: Evaluate the efficacy of SMA for improving psychosocial outcomes in adolescents with T1D.
Methods: Participants in the prospective Team Clinic study were randomized to attend SMA or individual appointments (usual care). They completed the Children’s Depression Inventory (CDI), Problem Areas in Diabetes (PAID), Diabetes Family Conflict Scale (DFCS), and Diabetes Strengths and Resilience (D-STAR) measures at baseline and after one year.
Results: Eighty-six adolescents (51% female; 74% white; 10% Latinx) completed at least one study visit. Team Clinic participants (n = 44) attended more visits than patients in usual care (n = 42; p &lt; 0.0001), and they attended all four study visits more frequently (66%) than those in usual care (33%). Although all adolescents reported nearly equal levels of depressive symptoms, emotional distress, and family conflict associated with diabetes care at baseline, significant differences emerged over the course of the study. Specifically, adolescents in Team Clinic reported reduced levels of conflict with family, while those in usual care reported slightly increased levels of conflict (p=0.03). Team Clinic adolescents also reported reduced depressive symptoms when compared to usual care, including more positive mood (p=0.001), greater self-esteem (p=0.03), improved effectiveness in completing daily tasks (p=0.03), and reduced anhedonia (p=0.04). Team Clinic adolescents also reported improved resilience and reduced emotional distress in diabetes care compared to controls, but these results were only marginally significant.
Conclusions: SMA may support adolescents with T1D in reducing familial conflict associated with diabetes care, while providing a decrease in comorbid depressive symptoms.

Disclosure
J. Raymond: Other Relationship; Self; Insulet Corporation. M.W. Reid: None. C. Berget: Consultant; Self; Insulet Corporation, Medtronic. C.L. Cain: None. B. Anderson: None. G.J. Klingensmith: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. Research Support; Self; Novo Nordisk Foundation. Stock/Shareholder; Spouse/Partner; Dexcom, Inc.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
2014-P: The Effect of High-Fat Diet on Adipose Tissue Glycerol Metabolism Is Influenced by Sex and GLP-1 Agonist Treatment
Authors: IENA FRANCESCO M. , VEGGER JENS BAY , THOMSEN JESPER SKOVHUS , BRÜEL ANNEMARIE , LEBECK JANNE 
Published: June 2019

During fasting triglyceride (TG) in adipose tissue (AT) is hydrolyzed into fatty acids and glycerol. Glycerol exits AT through the glycerol channel aquaporin 7 (AQP7). AQP7 KO mice have increased activity of AT glycerol kinase (GlyK), increased storage of TG, and become obese indicating that changes in AT glycerol metabolism influences TG storage. Moreover, in humans an association between low expression of AQP7 and obesity has been found in women only. This study aims to investigate whether high fat diet (HFD) influences AT glycerol metabolism in a sex-specific manner and whether the glycerol metabolism is influenced by GLP-1 agonist treatment. Female and male C57BL/6J mice (10 weeks) were fed a control diet or HFD for 12 or 24 weeks. The GLP-1 agonist Liraglutide was administered (SC, 1 mg/kg/day) to a subgroup of control and HFD fed female mice during the last 12 of the 24 weeks. Body weight (BW) and blood glucose (BG) were monitored and the expression of AQP7, GlyK, and lipolytic enzymes were investigated using immunoblotting of perigonadal AT and analyzed using Two-Way ANOVA. After 12 weeks, HFD increased BW by 34% in female and by 49% in male mice. BG levels were significantly increased in male mice only. After 24 weeks, HFD increased BW by 76% in female and by 49% in male mice and BG levels was significantly increased in both sexes. Liraglutide decreased both BW and BG levels compared to untreated controls. HFD increased the expression of AQP7 in female mice only and after 24 weeks of HFD this was paralleled by a more than 4-fold increase in GlyK and a 50% reduction in adipose triglyceride lipase abundance (ATGL). Liraglutide treatment normalized the expression of both AQP7 and GlyK. In male mice the abundance of GlyK was increased after 12 and 24 weeks of HFD.
In conclusion, HFD influences the expression of AQP7 in AT in a sex-specific manner. The increase in GlyK suggests an increased utilization of glycerol for TG synthesis in both sexes. Liraglutide treatment influences AT glycerol metabolism.

Disclosure
F.M. Iena: None. J. Vegger: None. J. Thomsen: None. A. Brüel: None. J. Lebeck: None.

Funding
Aarhus University
2015-P: 14-3-3zeta Is Required for PKA-Dependent Lipolysis
Authors: OPPONG ABEL , MUGABO YVES , LIM GARETH E. 
Published: June 2019

The molecular scaffold, 14-3-3?, was previously found to be essential for visceral adipogenesis, but its contributions to the function of mature adipocytes is not known. As it can regulate the activities of metabolic effectors, we hypothesized that 14-3-3? also has essential roles in adipocyte function.
3T3-L1 adipocytes and mouse models were used to study if 14-3-3? regulates lipolysis. Depletion of 14-3-3? by siRNA abrogated glycerol and free fatty acid (FFA) release from 3T3-L1 cells treated with Isoproterenol (ISO, 1 μM), Forskolin (FSK, 10 μM), and dibutyryl cAMP (1 mM). In contrast, over-expression of 14-3-3? potentiated ISO-mediated FFA release. Knockdown of 14-3-3? did not affect cAMP generation in ISO- and FSK-treated 3T3-L1 cells, but mRNA levels of lipases (Atgl, Hsl, and Magl) and Pparg were reduced, suggesting a loss of adipocyte identity. Decreased activation and total expression of PKA substrates, including Hsl and CREB, were detected in 14-3-3?-depleted 3T3-L1 cells. Taken together, these data suggest that 14-3-3? is necessary for lipolysis from 3T3-L1 adipocytes.
To understand adipocyte-specific roles of 14-3-3?, tamoxifen (TMX)-inducible, adipocyte-specific 14-3-3? knockout (adi14-3-3?KO) mice were used. Four weeks after TMX exposure (5 days, 50 mg/kg), no effects on body weight were found. After an overnight fast, adi14-3-3?KO mice displayed impaired lipolysis following i.p CL-316,243 (1 mg/kg) injections. In contrast, transgenic over-expression of 14-3-3? did not affect lipolysis. Adi14-3-3?KO mice also displayed glucose intolerance following i.p. glucose (2 g/kg). Real-time PCR confirmed significant reductions in Atgl, Hsl, and Pparg mRNA levels in adi14-3-3?KO mice, suggesting impaired adipocyte function.
Collectively, these results demonstrate essential functions of 14-3-3? in facilitating lipolysis and, potentially, adipocyte maturity. Future studies are aimed at understanding how 14-3-3? regulates other aspects of adipocyte function, including diet-induced expansion of fat mass.

Disclosure
A. Oppong: None. Y. Mugabo: None. G.E. Lim: None.

Funding
Canadian Institutes of Health Research
2019-P: Deletion of Hepatic SIRT1 Enhances the Effect of Ketogenic Diets on Ameliorating Obesity and Metabolic Disorders
Authors: GUO WANRONG , XU FEN , LI GUANGRONG , LIANG HUA , CAI MENGYIN 
Published: June 2019

A ketogenic diet, one kind of carbohydrate-restricted diets, is considered to reduce body weight and improve metabolic disorders. However, the mechanism of how a ketogenic diet provides such metabolic benefits is unclear. SIRT1, a NAD-dependent deacetylase, plays an important role in lipid metabolism. We investigated the role of hepatic SIRT1 in the beneficial effect of ketogenic diets on improving obesity and metabolic disorder. In this study, eight-week-old male liver-specific SIRT1 deletion (SIRT1 LKO) mice and control mice were subjected to a high fat diet (HFD) or an intermittent ketogenic diet (iKD), ketogenic diet alternated biweekly with HFD, for 12 weeks. The results showed that the body weight of mice fed on iKD was significantly lower than mice fed on HFD, even though higher energy intake was observed when mice were fed on a ketogenic diet. Interestingly, SIRT1 LKO mice on HFD were slightly heavier than control mice on HFD, but SIRT1 LKO mice on iKD were thinner than control mice on iKD. Lower fasting blood glucose was observed after every 2-week ketogenic diets intervention, and there was no significant difference between SIRT1 LKO mice and control mice. Compared to HFD, iKD significantly improved insulin resistance. Notably, iKD improved the glucose metabolism of SIRT1 LKO mice, but such improvement was not observed in control mice. These results indicate that an intermittent ketogenic diet improves metabolic disorders induced by HFD and has further beneficial effect on obesity and metabolic disorder in the absent of hepatic SIRT1. The underlying mechanism will be further studied.

Disclosure
W. Guo: None. F. Xu: None. G. Li: None. H. Liang: None. M. Cai: None.
203-LB: Comparison of Health-Related Quality of Life Between Elderly Men and Women with Diabetes in Korea
Authors: KANG HYUN SOOK 
Published: June 2019

Objective: This study aimed to identify the differences in health-related quality of life between elderly men and women with diabetes in Korea.
Methods: Health-related quality of life was measured using the Korean version of the EQ-5D (EuroQol 5-dimension). Using a descriptive study, this study incorporated a secondary analysis of the Korean version of the EQ-5D data from the 10th wave of the Korea Health Panel Survey in 2015.
Results: Total 1011 patients (aged ≥65 years), including 446 men and 565 women. The elderly Korean men with diabetes scored significantly higher on their quality of life than the elderly women with diabetes (t=-6.083, p=.000). The elderly women with diabetes had more problems in all EuroQol ED-5Q dimensions than did the elderly Korean men with diabetes. Subjective health status (t=-5.063, p=.000) and peer-to-peer health status (t=-5.073, p=.000) were also perceived to be worse among women compared with those among men. There were significant differences in education (X2=232.888, p=.000), marital status (X2=123.090, p=.000), economic activity (X2=185.585, p=.000), drinking status (X2=106.444, p=.000), physical activity (X2=35.581, p=.000), and visual acuity (X2=7.024, p=.030) among the elderly men and women with diabetes.
Conclusion: Based on these results, there is a need for specific health care programs targeting elderly women with diabetes that may help improve their health-related quality of life.

Disclosure
H. Kang: None.
2033-P: APX-115, a Pan-NADPH Oxidase (NOX) Inhibitor, Ameliorates Diabetic Nephropathy in NOX5 Transgenic Mice
Authors: LEE EUNSOO , CHUNG CHOON H. , HUH JI HYE , LEE SUN HEE 
Published: June 2019

Several studies verified that NOXs which is comprise isoform NOX1 to 5, Duox 1 and 2, trigger diabetic nephropathy incidences in diabetes. Recently, it has been studied that the expression of NOX5 is increased in the patients with diabetic nephropathy over other isoforms and the importance of NOX5 in the development of therapeutic agents has been suggested. Previous study investigated that APX-115 has the effect of pan-NOX inhibition in type 2 diabetic mice.
However, since the NOX5 gene is absent in the mouse, we evaluated the pan-NOX inhibitory of APX-115 in Nox5 transgenic mouse. Wild type and renal podocyte specifically NOX5 transgenic mice (NOX5 pod+) were fed high fat diet (60% kcal fat) and treated APX-115 (60mg/kg) by oral gavage for 14 weeks.
APX-115 significantly improved pancreatic beta cell function with decreased fasting blood glucose and increased insulin levels. And serum total cholesterol, triglycerides and urinary albumin/creatinine levels were also significantly decreased by APX-115 treatment. In NOX5 pod+ mice kidney, increased NOX5 mRNA expression, increased desmin and reduced podocin protein expressions were also significantly recovered by APX-115. Moreover, APX-115 inhibited inflammatory related protein expressions such as TRAF6.
Therefore, these data suggest that APX-115 might be a promising therapy for diabetic nephropathy by an efficacy as a pan-NOX inhibitor including NOX5 inhibition and anti-inflammatory effects.

Disclosure
E. Lee: None. C.H. Chung: None. J. Huh: None. S. Lee: None.
2053-P: Low AMY1 Gene Copy Number Is Associated with Increased Childhood Obesity in Alabama
Authors: KURAPATY VENKATAPOORNA CHANDRA MOHAN , AYINE PRISCILLA , PARRA EMILY P. , KOENIGS TAYLOR , SANDEY MANINDER , JEGANATHAN RAMESH B. , THANGIAH GEETHA 
Published: June 2019

Salivary amylase (AMY1) is the most abundant enzyme in human saliva, responsible for the hydrolysis of α-1,4 glycosidic linkages that aids in the digestion of dietary starch. Recently few studies have shown that copy number of AMY1 is associated with obesity, however, the data varies with different location. One-third of children are overweight/obese in Alabama. In this study, we specifically aim to determine the relationship between the copy number of AMY1 gene and obesity measurements in elementary school children from Alabama. Sixty elementary school children (30 normal weight and 30 overweight/obese) aged between 6 to 10 years participated in this study. Anthropometric measurements were measured using WHO recommendations. Saliva was collected, genomic DNA was extracted and the copy number of the AMY1 gene was estimated by digital PCR. Linear regression analysis was used to investigate the association between AMY1 copy number and obesity measurements. The mean AMY1 copy number was found to be significantly decreased in obese compared to normal weight children. The results showed a significant inverse association between obesity measurements and AMY1 copy number. Gender-specific analysis showed boys had a stronger association between low AMY1 copy number and obesity compared to girls. Our findings suggest that low AMY1 copy number plays a major role in childhood obesity in Alabama elementary school children and the effect is more prominent in boys compared to girls.

Disclosure
C. Kurapaty Venkatapoorna: None. P. Ayine: None. E.P. Parra: None. T. Koenigs: None. M. Sandey: None. R.B. Jeganathan: None. G. Thangiah: None.

Funding
National Institute of Food and Agriculture