bluuebunny/crossref_metadata_2025_split huggingface dataset:
1490-P: Levels of Specific Antibodies (Ab) for Sars Cov2 after Vaccination and Its Relationship with Clinical and Metabolic Variables in People with Type 2 Diabetes vs. Controls without Diabetes
Authors: POMARES MARIA L. , CUZZIOL GABRIELA , LOPEZ CLAUDIO E. , KREMER SENDROS SANDRA , POMARES DAMIAN , OJEDA MARIANA , WOLFFENBUTTEL CARLOTO VICTOR , TEJADA RINA M. , OJEDA GONZALO A. , FIGUERERO ANTONELA , GOMEZ MARTIN CAROLINA , GORBAN DE LAPERTOSA SILVIA 
Published: June 2023

Introduction: The COVID-19 pandemic has affected people all over the world, and even more seriously people with chronic pathologies.
Objectives: Primary: To evaluate the humoral immune response (IgG Ab specific for SARS CoV-2) in adults with DM2 versus controls. Secondary: To evaluate the relationship between Ab IgG levels and the presence of other clinical variables and comorbidities.
Materials and Methods: The study was carried out in January 2022 in Argentina. Adults with DM2 and controls who had received first and second doses of any SARS Cov-2 vaccines were included. Titers of Ac IgG were performed through the assay of IgG anti RBD (receptor binding domain in the host cell). Multiple Logistic Regression and Multiple Linear Regression were used. p value &lt;0.05 was considered statistically significant.
Results: N 144 participants (91 with DM2 and 53 controls). Median from the second dose of a vaccine to the measurement of Ab: 141 days in controls and 144 in diabetics (p=0.451). The logarithm of the Ab titers were significantly lower in patients with DM2 vs. controls (p&lt;0.01). Univariate analysis: Ab levels were positively and significantly related to BMI (p&lt;0.01). They were also significantly associated with age (p&lt;0.001) and with the presence of rheumatic diseases (p= 0.02). Multivariate analysis: Ab levels were only significantly and negatively associated with age (p&lt;0.01) and the presence of rheumatologic bone disease (p=0.02). No differences were found between the type of vaccines used.
Conclusion: Although the Ab titers registered in DM2 were significantly lower vs. controls, the adjustment for various covariates have not allowed to sustain the significance of this association in multivariate analysis. The role of age, BMI, the presence of rheumatic diseases and other factors should be explored in other studies in order to evaluate their potential role as confounders.

Disclosure
M.L.Pomares: None. A.Figuerero: None. C.Gomez martin: None. S.Gorban de lapertosa: None. G.Cuzziol: None. C.E.Lopez: None. S.Kremer sendros: None. D.Pomares: None. M.Ojeda: None. V.Wolffenbuttel carloto: None. R.M.Tejada: None. G.A.Ojeda: None.
1498-P: Preemptive Insulin Supplementation for Islet Graft Protection, Optimal Blood Glucose Control, and Fetal Development during the Pregnancy in Insulin-Independent Patient after Islet Transplantation
Authors: GONDEK SARAH , OGLEDZINSKI MATEUSZ , LIN WILLIAM , MILEJCZYK KAMILA , JUENGEL BRADEN , POTTER LISA , BACHUL PIOTR J. , BASTO LINDSAY , PEREA LAURENCIA , WANG LINGJIA , TIBUDAN MARTIN , BARTH ROLF , FUNG JOHN , WITKOWSKI PIOTR 
Published: June 2023

Pregnancy increases metabolic demand for insulin, which may lead to the exhaustion of intraportally transplanted islets and postgestational hyperglycemia. Here we report a successful long-term preservation of islet graft function after two subsequent pregnancies while applying preemptive insulin supplementation. 29-year-old female with T1DM achieved long-term insulin independence with HbA1c &lt;5.8% after a single intraportal islet transplant. Before conception, mycophenolate was replaced with azathioprine and tacrolimus target trough level was decreased to 4-6ng/ml. The patient became pregnant twice, 5 years and 7.5 years after her islet transplantation. During the first and second pregnancy patient preemptively supplemented with insulin up to 35-70u/day and up to 35 units daily, respectively to target fasting blood glucose below 90mg/ml. Postpartum the patient was successfully weaned off insulin maintaining optimal blood glucose control with HbA1c below 5.7%. Islet graft function before and after the pregnancy remained optimal as reflected by BETA-2 above 17 and comparable c-peptide secretion and peak blood glucose levels below 130mg/ml during the 8.5-year follow-up in Mixed Meal Tolerance Test. Both newborns were premature and delivered at 34 weeks with emergent c-sections due to preeclampsia. Unfortunately, the first newborn died due to necrotizing enterocolitis. The second child has been developing appropriately up-to-date three months after her birth. Our report confirms that insulin supplementation during pregnancy in insulin-independent patients after islet transplantation was safe and effective in maintaining optimal blood glucose control and islet graft function in the long term. It also underscores the high-risk nature of pregnancy in islet transplant recipients and the need for close clinical monitoring.

Disclosure
S.Gondek: None. L.Wang: None. M.Tibudan: None. R.Barth: None. J.Fung: None. P.Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novartis. M.Ogledzinski: None. W.Lin: None. K.Milejczyk: None. B.Juengel: None. L.Potter: None. P.J.Bachul: None. L.Basto: None. L.Perea: None.
15-LB: Serum Tsukushi Is Associated with Urinary Albumin Excretion in Type 2 Diabetes
Authors: LI YAN Y. 
Published: June 2023

Background: Tsukushi (TSK) is a newly identified hepatokine that is associated with lipid and glucose metabolism. Although hyperglycemia, hyperlipemia and metabolic disorder are associated with diabetic nephropathy (DN) development, there is currently no investigation about whether TSK is associated with urinary albumin-creatinine ratio (UACR) and renal function.
Methods: Serum TSK level was quantified by ELISA in 167 normoalbuminuria, 80 microalbuminuria, 31 macroalbuminuria patients with T2DM as compared with 53 healthy subjects. Multiple linear regression and logistic regression analysis were used to analyze the relationship of TSK or other characteristics with UACR and eGFR.
Results: The TSK level in the all T2DM group was prominently higher than that in the control group. Further, TSK level in macroalbuminuria group was significantly higher than normoalbuminuria and microalbuminuria. Multiple linear regression showed that high TSK quartile, systolic pressure, serum creatinine, HOMA-IR, low 2-h post-OGTT glucose and female were the significantly independent factors for UACR. Logistic regression demonstrated that the OR of TSK for eGFR ≤ 90 was 1.636 (95%CI 1.091-2.452, P=0.017).
Conclusion: The circulating TSK increased in T2D patients with albuminuria and associated with UACR and eGFR, implied that TSK may involve in the pathogenesis of DN, which deserved future studies.

Disclosure
Y. Y. Li: None.

Funding
Talents Training Program of Shanghai Pudong Hospital (YQ202101); Social Development Project of Jiangsu Province (BE2018692); Natural Science Foundation of Jiangsu Province (BK20191222)
1508-P: ZnPP-Laden Nanoparticles Improve Glucose Homeostasis and Chronic Inflammation during Obesity
Authors: YANG WANBAO , ARORA MEENAKSHI , HAN HYEWON , JIANG WEN , MI KIM DA , AI WEIQI , PAN QUAN , RAVI KUMAR M.N.V. , BRASHEAR WESLEY , SUN YUXIANG , GUO SHAODONG 
Published: June 2023

Type 2 diabetes mellitus (T2DM) characterized by insulin resistance has become a serious health threat. Chronic inflammation is believed to play a pivotal role in the development of T2DM. Previous study has shown that HO-1 plays an anti-inflammatory role, suggesting HO-1 inhibition could be an effective strategy to treat T2DM. However, application of HO-1 inhibitors is restricted due to their low solubility. In this study, we detected the role of HO-1 inhibitor, ZnPP, in regulating glucose homeostasis and inflammation during obesity. We encapsulated ZnPP with nanoparticles to increase its water solubility and delivered ZnPP-laden nanoparticles (Nano-ZnPP) to the obese mice. We found that inhibition of HO-1 by Nano-ZnPP significantly decreases adiposity, increases insulin resistance, and improves glucose tolerance in diet-induced obesity mice. Moreover, Nano-ZnPP treatment attenuated both local and systematical inflammatory levels during obesity. Mechanistically, Nano-ZnPP significantly attenuated glucagon, TNF, and fatty acid synthesis signaling pathway in liver. In white adipose tissue, oxidative phosphorylation signaling pathway was enhanced and inflammation signaling pathway was diminished by Nano-ZnPP. Our results showed that Nano-ZnPP has a better effect on improving glucose homeostasis and attenuating chronic inflammation, as compared to DMSO-dissolved ZnPP. These results indicate that ZnPP-laden nanoparticles could be a potential therapeutic agent to treat T2DM.

Disclosure
W.Yang: None. Y.Sun: None. S.Guo: None. M.Arora: None. H.Han: None. W.Jiang: None. D.Kim: None. W.Ai: None. Q.Pan: None. M.Kumar: None. W.Brashear: None.

Funding
National Institutes of Health (R01DK095118, R01DK120968, R01DK118334, R01AG064869)
1512-P: The Novel Roles of Intracellular Calcium and Phosphoinositides in Insulin Signaling and Metabolic Disease
Authors: LEE JIN-WOOK , JUNG YUNJAE , IM SEUNG-SOON , HO LEE DAE , LEE HWA-YONG , SUN HONG IN , KIM OK-HEE , OH BYUNG-CHUL 
Published: June 2023

Insulin resistance is closely associated with elevated intracellular Ca2+ concentration under ectopic lipid accumulation and hyperglycemia-induced intracellular stress conditions. We recently identified that obesity impairs intracellular Ca2+ homeostasis, which prevents membrane localization of PH domain-containing proteins such as AKT, PLCδ, and IRS through the formation of Ca2+-phosphoinositides (PIPs), resulting in dysregulation of glucose homeostasis and insulin resistance. It is unclear, however, whether insulin sensitivity can be improved by targeting intracellular Ca2+ overload. Therefore, we screened nine angiotensin-II-receptor blockers (ARBs), a class of antihypertensive agents, for beneficial effects on palmitic acid (PA)-induced insulin resistance in human HepG2 cells. Two of the ARBs attenuated PA-induced intracellular Ca2+ overload by inhibiting dysregulated store-operated channel (SOC)-mediated Ca2+ entry into cells, which ameliorated insulin resistance by promoting insulin-stimulated membrane localization of AKT and by increasing the phosphorylation of AKT and its downstream substrates in PA-treated HepG2 cells. Furthermore, certain ARBs ameliorated obesity-induced insulin resistance, hepatic steatosis, and tissue inflammation in mice fed a high-fat diet. Meanwhile, certain ARBs normalized intracellular Ca2+ homeostasis by regulating obesity-associated SOC-mediated Ca2+ entry, which rescued impaired insulin signaling in liver and muscle tissues by promoting postprandial membrane localization of AKT and IRS2. These findings underscore the contribution of dysregulated intracellular Ca2+ homeostasis to the pathophysiology of insulin resistance and suggest a therapeutic strategy to use specific ARBs to ameliorate insulin resistance.

Disclosure
J.Lee: None. Y.Jung: None. S.Im: None. D.Lee: None. H.Lee: None. I.Hong: None. O.Kim: None. B.Oh: None.

Funding
Korean Ministry of Health & Welfare (HI14C1135 to B-C.O.); Basic Science Research Program (2021R1I1A1A01051429 to O-H.K.); Mid-Career Researcher Program (2019R1A2C2008130, 2022R1A2C2092700 to B-C.O.); National Research Foundation of Korea (2021R1A5A203033)
1531-P: Preoptic Anterior Hypothalamus Estrogen Signaling Controls Energy and Temperature Homeostasis
Authors: LUO PEI , YANG XIAOHUA , FENG BING , YE HUI , ANTONY NIMISHA , CARRILLO-SÁENZ LESLIE , TORRES IRIZARRY VALERIA C. , LAYDEN BRIAN T. , HE YANLIN , XU PINGWEN 
Published: June 2023

An ovarian hormone, estrogen, has been shown to act on the preoptic anterior hypothalamus (POA) to modulate temperature and energy homeostasis. However, the underlying neural mechanism is still largely less known. Interestingly, we found that POA neurons express high levels of estrogen receptor α (ERα) and β (ERβ), and a subpopulation of POA neurons co-express ERα and ERβ (ERα/βPOA). We showed that ERα agonist stimulates ERα/βPOA neurons, whereas ERβ agonist inhibits ERα/βPOA neurons. Estrogen17β-estradiol (E2) showed mixed actions in the ERα/βPOA neurons, presumably caused by the counterbalance between ERα and ERβ. This dynamic counterbalance may lead to distinct effects of E2 in regulating temperature and energy balance depending on temperature or nutritional status. Consistently, chemogenetic activation of ERαPOA decreased food intake, brown adipose tissue (BAT) thermogenesis, and body temperature, mimicking warm-induced adaptation. Conversely, inhibition of ERβPOA neurons increases food intake, BAT thermogenesis, and body temperature, mimicking cold-induced adaptation. In conclusion, these results support a model that ERα/βPOA neurons service as an integrating center for the estrogenic regulation of temperature and energy homeostasis.

Disclosure
P.Luo: None. P.Xu: None. X.Yang: None. B.Feng: None. H.Ye: None. N.Antony: None. L.Carrillo-sáenz: None. V.C.Torres irizarry: None. B.T.Layden: Consultant; Bayer Inc. Y.He: None.

Funding
National Institutes of Health (R01DK123098, P30DK020595 to P.X.), (P20GM135002, R01DK129548 to Y.H.), (T32AA026577 to V.C.T.I.); American Heart Association (915789 to V.C.T.I.), (20POST35120600 to Y.H.); U.S. Department of Defense (W81XWH-20-1-0075 to P.X
1548-P: GLP-1 and GIP Reduce Insulin Clearance in Individuals with Pancreatic-Insufficient Cystic Fibrosis (PI-CF)
Authors: FLATT ANNELIESE , DOLIBA ANDRIANA , PELECKIS AMY J. , RUBENSTEIN RONALD C. , KELLY ANDREA , RICKELS MICHAEL R. 
Published: June 2023

PI-CF is characterized by impaired insulin secretion with disruption of the enteroinsular axis and alterations in incretin secretion and action. We have reported augmented glucose-dependent insulin secretion to glucose-potentiated arginine (GPA) testing with GLP-1 infusion but not GIP, with these effects independent of glucose tolerance in PI-CF.
We aimed to assess the effect of incretin infusion on insulin clearance during GPA testing and explore its relationship to second-phase insulin response in individuals with PI-CF in a retrospective analysis. Thirty-two individuals with PI-CF and abnormal glucose tolerance underwent GPA testing of islet function following intravenous infusion of incretin or placebo in a randomized cross-over study design. Sixteen individuals were randomized to incretin infusion with GLP-1 and sixteen with GIP. Insulin clearance was assessed by the molar ratio of acute C-peptide to insulin response over the 5-minutes following glucose-potentiation of arginine-induced insulin and C-peptide secretion (target glucose ~230 mg/dL).
Insulin clearance was related to second-phase insulin secretion by hyperbolic function (y=P1/(P2 + x) with a reduction in insulin clearance for increasing second-phase insulin secretion (R2=0.20; p&lt;0.001). A reduction in insulin clearance was observed with both GLP-1 vs. placebo (mean±SD 2.7±2.1 vs. 15.5±5.7; p&lt;0.001) and GIP vs. placebo (2.4±0.8 vs. 18.0±10.8; p&lt;0.001).
GLP-1 and GIP appear to reduce insulin clearance in individuals with PI-CF presumably through effects at the liver. Reduced insulin clearance is most apparent following GIP infusion where there is no augmentation of second-phase insulin secretion, supporting that the effect of GIP occurs independently of an increase in pre-hepatic insulin secretion. Further work should explore underlying mechanisms of incretin-induced reduction in insulin clearance in PI-CF that could support therapeutic approaches to improve glucose homeostasis.

Disclosure
A.Flatt: None. A.Doliba: None. A.J.Peleckis: None. R.C.Rubenstein: None. A.Kelly: None. M.R.Rickels: Consultant; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Research Support; Dompé.

Funding
National Institutes of Health (R01DK97830, UL1TR001878, P30DK19525, T32DK007314); Cystic Fibrosis Foundation (to M.R.R.)
1554-P: Carnosic Acid Protects against Short-Term Lipid-Infusion–Induced Glucose Intolerance in Mice
Authors: TSAKIRIDIS NICOLE , VLAVCHESKI FILIP , TSIANI EVANGELIA , GIACCA ADRIA 
Published: June 2023

Background: Obesity and type 2 diabetes (T2D) are associated with elevated plasma free fatty acids (FFA). In vivo exposure to FFAs, such as palmitate, by lipid infusion results in insulin resistance as observed in obesity and T2D. In recent years, compounds found in herbs and plants have attracted attention for prevention and treatment of insulin resistance and T2D. In recent studies by our group, carnosic acid (CA), found in rosemary, increased glucose uptake and attenuated the FFA (palmitate)-induced insulin resistance in muscle cells and adipocytes. In addition, CA caused a robust activation of AMP-activated protein kinase (AMPK). Our present study aimed to examine the effects of CA in short-term FFA-induced glucose intolerance in mice.
Material and Methods: C57Bl/6J mice were cannulated in their jugular veins and infused for 48h with ethylpalmitate (EtP, nontoxic method of elevating circulating palmitate because of hydrolysis to palmitate and ethanol by plasma esterases), mimicking elevated FFA levels seen in obesity. In addition, a group of mice were infused with EtP plus 50 mg/kg CA for 48h. Ethanol vehicle with or without CA were two additional control groups. At the end of the infusions, the mice were subjected to a 2 hr hyperglycemic clamp (20 mM glucose) and the glucose infusion rate was measured to assess glucose tolerance.
Results: Preliminary data revealed that mice infused with EtP and CA had a higher glucose infusion rate (GIR; mg/kg*min) (66.5±10, mean±SEM) than mice infused with EtP alone (22.7±10). The EtP and CA was comparable to the GIR of ethanol vehicle infused mice (73±9).
Future Directions: Further analysis of collected plasma and tissue will be used to assess insulin resistance and beta cell function in vivo and to elucidate the mechanisms of CA alleviation of FFA-induced insulin resistance.
Conclusions: Our data indicate that CA has the potential to counteract FFA-induced glucose intolerance in mice.

Disclosure
N.Tsakiridis: None. F.Vlavcheski: None. E.Tsiani: None. A.Giacca: None.
1558-P: The Mitochondrial Calcium Uniporter Regulates Hepatic Mitochondrial Oxidation and Intracellular Redox In Vivo
Authors: LAMOIA TRACI E. , HUBBARD BRANDON T. , GUERRA MATEUS , GOODMAN RUSSELL , NATHANSON MICHAEL H. , SHULMAN GERALD I. 
Published: June 2023

The mitochondrial calcium uniporter (MCU) facilitates mitochondrial calcium influx, and several enzymes that catalyze key steps of the TCA cycle require calcium for their activation. As such, it is generally accepted that rates of mitochondrial oxidation correlate with mitochondrial calcium activity. Decreased rates of hepatic mitochondrial oxidation are associated with metabolic dysfunction and ectopic lipid accumulation as seen with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. Despite this, a role for MCU and mitochondrial calcium in regulating hepatic mitochondrial oxidation is still unclear. To address this question, we generated a liver-specific MCU knockout (MCU KO) mouse model which displayed reduced mitochondrial calcium ([Ca2+]mt; p&lt;0.05) and increased cytosolic calcium ([Ca2+]cyt; p&lt;0.01). Despite decreased [Ca2+]mt, we found that deletion of hepatic MCU increased rates of isocitrate dehydrogenase flux (VIDH; p&lt;0.01), α-ketoglutarate dehydrogenase flux (VOGDH; p&lt;0.01), and succinate dehydrogenase flux (VSDH; p&lt;0.05) in vivo, using a novel [13C5]glutamine tracer infusion technique (Q-Flux). Further, we show that rates of [14C16]palmitate oxidation (p&lt;0.01) and intrahepatic lipolysis (p&lt;0.05) were significantly increased in liver slices collected from MCU KO mice compared to WT mice, and were associated with reductions in hepatic triacylglycerol content in vivo (p&lt;0.01). Hepatocellular redox state was also altered with MCU KO, as indicated by a decreased cytosolic redox ratio ([lactate]:[pyruvate]; p&lt;0.05) and increased mitochondrial redox ratio ([β-hydroxybutyrate]:[acetoacetate]; p&lt;0.01).
Conclusion: Here we show that increases in [Ca2+]cyt potently increase hepatic mitochondrial fat oxidation and alters hepatic redox balance to reduce hepatic lipid content independently of [Ca2+]mt in vivo and targeting [Ca2+]cyt may represent a novel therapeutic target to treat NAFLD.

Disclosure
T.E.Lamoia: None. B.T.Hubbard: None. M.Guerra: None. R.Goodman: None. M.H.Nathanson: None. G.I.Shulman: Consultant; Novo Nordisk, DiCerna Pharmaceuticals, Inc., Bayer Consumer Care AG, Kriya Therapeutics, Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Other Relationship; AstraZeneca, Merck & Co., Inc., Janssen Research & Development, LLC, iMetabolic Biopharma Corporation, Maze Therapeutics, 89bio, Inc., Equator Therapeutics, Inc., Generian Pharmaceuticals, Fortress Biotech, Inc., OrsoBio, Aro Biotherapeutics Company, Stock/Shareholder; Levels Health, Inc.

Funding
National Institutes of Health (F31DK126362, T32GM007324)
1585-P: MAFLD in Obesity with Deteriorating Glucose Control
Authors: FORST THOMAS , BOTZ ISABEL , BERSE MATTHIAS , BAUMANN SYBILLE K. , SCHULTZ ARMIN 
Published: June 2023

The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rising in parallel with increasing bodyweight and loss of glucose control, implicating a high risk of hepatic and extra-hepatic complications. This longitudinal observational study analysed several indicators for MAFLD in 240 overweight subjects (body mass index (BMI) &gt; 28 kg/m²) at 2 visits within in average 16 months. Subjects were categorised according to their insulin sensitivity (HOMAIR) and diabetic status. Liver fat and liver stiffness were measured with sonographic elastography (FibroScan®), and by calculation of Fatty Liver Index (FLI), and NAFLD Fibrosis Score (NFS). Parameters indicative for liver steatosis, i.e., the controlled attenuation parameter (CAP) and the FLI, were significantly higher in the T2DM group compared to the normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) groups (p&lt;0.05). FLI values and the HOMAIR significantly correlated with sonographic liver fat content (CAP) (r=0.53, p&lt;0.0001; r=0.34, p&lt;0.001, respectively). An inverse correlation was observed between serum adiponectin levels and CAP (r=-0.20; p&lt;0.019) and adiponectin levels and FLI (r=-0.37; p&lt;0.0001). Over 16 months, fasting insulin levels and HOMAIR score increased mainly driven by the group of obese subjects with T2DM. No significant change in liver fat or stiffness was observed that period.
In subjects with a BMI ≥ 28kg/m², the prevalence of MAFLD increases in line with increasing insulin resistance and loss of glucose control. Despite some further deterioration in insulin sensitivity, liver fat content appeared relatively unchanged over 16 months.

Disclosure
T.Forst: Consultant; Pfizer Inc., Speaker's Bureau; Amarin Corporation, AstraZeneca, Boehringer Ingelheim Inc., Cipla Inc., Daiichi Sankyo, Eli Lilly and Company, MSD Life Science Foundation, Novo Nordisk, Sanofi. I.Botz: None. M.Berse: None. S.K.Baumann: None. A.Schultz: None.