bluuebunny/crossref_metadata_2025_split huggingface dataset:
1593-P: Insulin-Degrading Enzyme (IDE) Regulates Glucagon Signalling and Mitochondrial Respiration in Hepatocytes
Authors: GONZÁLEZ-CASIMIRO CARLOS M. , CÁMARA-TORRES PATRICIA , MERINO BEATRIZ , SANTO-DOMINGO JAIME , DE LA FUENTE MIGUEL A. , ALONSO ANDRÉS , COZAR-CASTELLANO IRENE , PERDOMO GERMAN 
Published: June 2023

IDE is a ubiquitous metalloprotease with cytosolic and mitochondrial subcellular localization that degrades insulin and glucagon. People with T2D and diet-induced obese mice show lower hepatic IDE levels. We revealed a key role of IDE on the insulin-mediated repression of hepatic gluconeogenesis, but its function on glucagon-dependent activation of gluconeogenesis and mitochondrial respiration in hepatocytes remains completely unknown. Here, we aim to elucidate the role of IDE on glucagon signalling and its impact on gluconeogenesis and energy metabolism in hepatocytes. Liver homogenized and primary hepatocytes obtained from L-IDE-KO mice (deletion of IDE in liver) showed decreased expression of glucagon receptor (~60%), CREB protein (~40%), and lower phosphorylation of CREB (~50%) upon glucagon stimulation compared to controls. Similar results were found in AML12-shRNA-Ide cells, in which IDE protein levels were reduced by ~50%. Additionally, glucagon stimulation resulted in lower (~30%) cAMP levels and diminished phosphorylation of PKA substrates in AML12-shRNA-Ide. Surprisingly, these alterations in glucagon signalling paralleled with ~20-fold increases in the expression of the gluconeogenic genes G6p6 and Pck1. Of note, basal and uncoupler-stimulated respiration increased ~4-fold in AML12-shRNA-Ide in parallel with a ~2-fold increment of mitochondrial and glycolytic ATP production. Finally, similar mitochondrial phenotype was found in human hepatocytes lacking IDE (HepG2-IDE-KO cells), which exhibited higher FoxO1 levels and fragmented mitochondria. The effects on mitochondrial respiration were independent of IDE's proteolytic activity.
In summary, reduced IDE expression in hepatocytes has a deleterious effect on glucagon signalling leading to up-regulated gluconeogenesis and mitochondrial respiration. We conclude that IDE is a mechanistic link to couple hepatic gluconeogenesis with mitochondrial energy production.

Disclosure
C.M. González-Casimiro: None. P. Cámara-Torres: None. B. Merino: None. J. Santo-Domingo: None. M.A. de la Fuente: None. A. Alonso: None. I. Cozar-Castellano: None. G. Perdomo: None.

Funding
Ministerio de Ciencia e Innovación-Spain (PID2019-110496RB-C22)
160-OR: Youth with T1D and Elevated A1C —Pandemic Experiences and Psychosocial Factors
Authors: WAGNER DAVID V. , RAYMOND JENNIFER , WONG JENISE C. , NARANJO DIANA , REED ALISON , TORRES KRISTEN A. , MELNICK SYDNEY , MITCHELL SUSANNE , YGLECIAS LOREN , FLORES GARCIA JAQUELIN , TORRES SANCHEZ ALEJANDRA , BONILLA OSPINA ANDREA , CLEMENTS MARK A. , HARRIS MICHAEL A. 
Published: June 2023

Background: Individuals with T1D and elevated A1c may be differentially impacted by the COVID-19 pandemic. We examined the pandemic experiences and psychosocial factors of youth with T1D and their families.
Methods: Youth 12-17 years of age with T1D for ≥1 yr and A1c ≥ 10% were enrolled at 5 sites. Caregivers and youth reported pandemic experiences, family functioning, parenting practices, social support, diabetes distress, and family-medical team relationship. Pandemic experiences were compared to benchmark data, and significant associations were examined.
Results: Participants (n=157) had mean age of 14.6 ± 1.6 years and mean A1c 11.0 ± 1.9%. Some pandemic experiences (e.g., change of schooling, loss of job) of youth with elevated A1c were similar to reports of other samples of youth with T1D, but youth with elevated A1c endorsed higher frequency of more severe COVID illness (43.9%), less strict social distancing (57.8%) and lower positive diabetes experiences (7.3%). Youth, caregiver, family, and family-medical team relationships were significantly associated with pandemic-related distress and T1D experiences during the pandemic (see Table).
Conclusion: Youth with elevated A1c reported more frequent negative pandemic experiences compared to other samples, with related youth, family, caregiver, and family-medical team factors identified as potential targets for screening and intervention.

Disclosure
D.V. Wagner: None. J. Raymond: None. J.C. Wong: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. D. Naranjo: None. A. Reed: None. K.A. Torres: None. S. Melnick: None. S. Mitchell: None. L. Yglecias: None. J. Flores Garcia: None. A. Torres Sanchez: None. A. Bonilla Ospina: None. M.A. Clements: Consultant; Glooko, Inc. Research Support; Dexcom, Inc., Abbott Diabetes. M.A. Harris: None.

Funding
JDRF
1601-P: Childhood Plasma Amino Acid Profiles Predict the 10-Year Risk of Nonalcoholic Fatty Liver Disease—The BCAMS Study
Authors: LI MING , GAO SHAN ,   BCAMS GROUP
Published: June 2023

Background and Aims: Amino acid profiles have been proved a promising tool to identify novel biomarkers and insight of the mechanisms of metabolic diseases; however, date on youth was still limited, particularly nonalcoholic fatty liver disease (NAFLD). We aimed to prospectively investigate if there exist any association between childhood plasma amino acid profiles and adulthood NAFLD, and explore the early predictor and the underlying mechanism for the development of hepatic steatosis.
Methods: A total of 307 subjects aged 12.1±3.0 years at baseline were enrolled in this study at 10-year follow-up, recruited from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study cohort, including 99 NAFLD patients and 208 normal controls. Thirty-two amino acids (AAs) in fasting plasma at baseline were evaluated by liquid chromatograph-mass spectrometry. NAFLD was diagnosed by abdominal ultrasonography at follow-up.
Results: Among the 32 qualified AAs, 14 AAs showed significant differences (p&lt;0.05) between NAFLD and normal controls, including four AAs survived Bonferroni correction (p&lt;0.0016). Adjustment for age, gender and lifestyle factors, there were 10 AAs remain significant, including alanine, asparagine, glutamine, glycine, isoleucine, tyrosine, serine and threonine etc. Further adjustment for BMI, lower levels of asparagine (OR: 0.62, 95% CI: 0.44-0.87), glutamine (OR: 0.73, 95% CI: 0.53-0.99) and serine (OR: 0.71, 95% CI: 0.51-0.98) remain significant predictors of NAFLD at the 10-year follow-up.
Conclusion: Plasma amino acid profiles in childhood can predict risk of NAFLD in young adults. Plasma asparagine, glutamine and serine are likely to be early predictors of NAFLD independently of adiposity.

Disclosure
M.Li: None. S.Gao: None. Bcams group: n/a.

Funding
National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014); National Natural Science Foundation of China (81970732, 82270924); Capital's Funds for Health Improvement and Research (2020-2Z-40117); CAMS Innovation Fund for Medical Sciences (C
1603-P: Differential Effects of Cocoa Butter, Sunflower, Soybean, and Fish Oil Based Sucrose-Free HFDs on Hepatic Steatosis, Lipogenesis, Inflammation, and Insulin Resistance in Mice
Authors: AHMAD RASHEED , JACOB TEXY K. , KOCHUMON SHIHAB P. , THOMAS REEBY S. , SHENOUDA STEVE , AKHTER NADEEM , WILSON AJIT , BAHMAN FATEMAH , HASAN AMAL , ALRASHED FATEMA , AREFANIAN HOSSEIN , AL MADHOUN ASHRAF , ALMULLA FAHD , SINDHU SARDAR T.A.K. 
Published: June 2023

Nonalcoholic fatty liver disease (NAFLD) is a risk factor of type-2 diabetes and cardiovascular disease. Obesity induced by various high-fat diets from different sources results in different types of meta-inflammatory derangements, including NAFLD. Fats are a central part of healthy diets, however, the impact of various dietary fats, lacking in sucrose, on liver fat accumulation and expression of lipogenic and inflammatory markers remains unclear. To study this, C57BL/6J mice were fed sucrose-free HFDs comprising fat from diverse sources, including cocoa butter (c-HFD), sunflower oil (s-HFD), soybean oil (so-HFD), and fish oil (f-HFD). Mice fed c-HFD or so-HFD developed more severe liver steatosis, compared with those fed s-HFD or f-HFD. Liver histopathology displayed high levels of lobular inflammation in mice fed c-HFD, so-HFD, and s-HFD. Kupffer cell counts were higher in mice fed c-HFD and s-HFD. Hepatic fibrosis was seen in mice fed s-HFD or so-HFD. Of note, there was no hepatic fibrosis in mice fed f-HFD. None of the diet had a significant impact on total body weight. However, liver weight was slightly increased in mice fed c-HFD or s-HFD. Mice fed c-HFD, s-HFD, and so-HFD displayed insulin resistance. Expression of the key genes of glycolysis (Pklr), de novo lipogenesis (Acaca, Fasn, Scd1), fatty acid oxidation (Cpt1a, Ppar-α), inflammation (Tnf-α) was upregulated in mice fed c-HFD or s-HFD. No significant difference was seen regarding genes of fatty acid uptake (Cd36, Fabp2), and chemokine-associated inflammation (Ccl2). Interestingly, hepatic IL-1β and IL-6 were elevated only in mice fed c-HFD. Taken together, these findings indicate that mice fed the sucrose-free HFDs comprising lipids from various dietary sources may have differential effects on hepatic steatosis at levels of de novo lipogenesis, hepatic inflammation, and whole-body insulin resistance.

Disclosure
R. Ahmad: None. T.K. Jacob: None. S.P. Kochumon: None. R.S. Thomas: None. S. Shenouda: None. N. Akhter: None. A. Wilson: None. F. Bahman: None. A. Hasan: None. F. Alrashed: None. H. Arefanian: None. A. Al Madhoun: None. F. Almulla: None. S.T.K. Sindhu: None.

Funding
Kuwait Foundation for the Advancement of Sciences (RAAM-2016-007)
1616-P: Effects of Hazelnuts Consumption Combined with Physical Activity on Lipid Metabolism and Correlations with Marrow Adiposity Homeostasis
Authors: FERRULLI ANNA , MASSARINI STEFANO , MACRÌ CONCETTA , SENESI PAMELA , TERRUZZI ILEANA , ROSSO GINEVRA , CHARRON MELANIE , MENTA ROBERTO , LUZI LIVIO 
Published: June 2023

Consumption of hazelnuts has been associated with reduced cardiovascular risk and improved metabolic outcomes. Furthermore, the Bone Marrow Fat (BMF) might contribute to skeletal as well as systemic metabolism, modulating insulin sensitivity and, consequently, cardiovascular risk. Previously, we demonstrated a beneficial effect of hazelnuts and cocoa integration on vascular reactivity and metabolic profile in healthy individuals. Aim of this randomized controlled interventional study with 3 parallel groups was to investigate the effects of a daily supplementation with 30 g of hazelnuts, with or without aerobic physical activity (PA), throughout 8 weeks, on insulin sensitivity and resistance, lipid profile, and on BMF content (evaluated by proton magnetic resonance spectroscopy) in healthy individuals. Twenty-five adults (age 18-50 yrs; BMI 18-28 Kg/m2) were randomized in 3 groups: 9 subjects (5F/4M, age 25.6±8.8 yrs, BMI 23.3±2.5) received 30 g of hazelnuts associated with diet (Group 1); 9 subjects (6F/3M, age 26.3±6.3 yrs, BMI 22.0±2.1) received 30 g of hazelnuts associated with diet and aerobic PA (Group 2); 7 subjects (4 F/3 M, age 29.7±6.4 yrs, BMI 23.3±4.2) received only diet (Group 3). After the 8 weeks-intervention, an improvement in LDL-Cholesterol was found in Groups 1 and 2 [-9.3±11.5% (Group 1) vs -5.0±13.6% (Group 2) vs +21.9±35.7% (Group 3); p=0.02]. BMF content variation negatively correlated with LDL-Cholesterol change in Group 1 (r=-0.802, p=0.054); variations in BMF content and in HDL-Cholesterol positively correlated in Group 2 (r=+0.8687, p=0.011). This study confirms the beneficial effects of hazelnuts, in association with PA in improving lipid profile. The correlations between HDL- and LDL-cholesterol and BFM changes suggest an impact of bone homeostasis on whole-body lipid metabolism, through a rapid utilization of lipids, drawing them out of the circulation and decreasing their deposition in the organ tissues.

Disclosure
A.Ferrulli: None. S.Massarini: None. C.Macrì: None. P.Senesi: None. I.Terruzzi: None. G.Rosso: Employee; Soremartec Italia Srl, Ferrero Group. M.Charron: Employee; Soremartec Italia Srl, Ferrero Group. R.Menta: Employee; Soremartec Italia Srl, Ferrero Group. L.Luzi: Advisory Panel; Eli Lilly and Company, Medtronic, Research Support; Gelesis, Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Novo Nordisk, Novartis.

Funding
IRCCS MultiMedica (Ricerca Corrente)
162-LB: ¡Más Fresco! More Fresh—Impact of a Fruit and Vegetable Prescription Program in a Pediatric Type 2 Diabetes Clinic
Authors: CHAN KAREN , HILLER-VENEGAS SARAH P. , KIM JANE J. , KLEIN KAREN O. , RHEE KYUNG 
Published: June 2023

Fruit and vegetable prescription (FVRx) programs have shown to improve fruit and vegetable intake and glycemic control in adults with diabetes; however, pediatric data is lacking. The aim of this study was to assess if a FVRx program improved fresh fruit and vegetable intake and health outcomes of children with type 2 diabetes mellitus (T2D). Families with a child with T2D and enrolled in Medi-Cal were recruited from our pediatric diabetes clinic. Families were randomized to either receive vouchers immediately (intervention group) or after a 6-month waiting period (delayed-control group). Monthly vouchers were given for 1 year to purchase fresh fruits and vegetables. Families completed surveys including the Dietary Screening Questionnaire and U.S. Household Food Security Survey every 6 months. Physiologic data and standardized laboratory tests were also collected. Of the 57 families with baseline surveys, the majority identified as Latino/Hispanic (84%) and the mean age of children was 14.3 years. Of the 49 parents who completed the baseline U.S. Household Food Security Survey, 46.9% reported low household food security and 16.3% reported very low food security. There were 29 families who completed our baseline and 6-month surveys. For the intervention group (n=14), there was an increase in parent-reported fruit and vegetable intake from baseline to 6-months for parents (2.4 vs 3.6 cups per day, p=0.0034) and children (2.6 vs 4.4 cups per day, p=0.0264). Children self-reported increased fresh vegetable intake between baseline and 6-months (0.17 vs 0.53 cups per day, p=0.014). There was no statistically significant difference in these measures for the delayed-control group (n=15). There was no significant change in BMI Z-score or hemoglobin A1c for the two groups after 6 months. A FVRx program is a viable intervention to improve fruit and vegetable intake for families with a child with T2D. Further research is needed to assess its impact on BMI and glycemic control.

Disclosure
K. Chan: None. S. P. Hiller-venegas: None. J. J. Kim: None. K. O. Klein: Consultant; AbbVie Inc., Tolmar Pharm, Azurity. K. Rhee: None.

Funding
U.S. Department of Agriculture-National Institute of Food and Agriculture (2021-06512)
1620-P: Royal Jelly Improved Dysbiosis and Glucose Intolerance in db/db Mice
Authors: OKAMURA TAKURO , HAMAGUCHI MASAHIDE , OKAMOTO HIDETO , OKUMURA NOBUAKI , FUKUI MICHIAKI 
Published: June 2023

In this study, we have investigated the mechanisms of improvement of glucose intolerance via changes in gut microbiota using db/db mice. Eight-week-old db/m and db/db mice were divided into 5 groups and housed for eight weeks (n=6 for each group): db/m group without RJ (db/m), db/db mice without RJ (db/db), db/db mice with 0.2% RJ (db/db + 0.2% RJ), db/db mice with 1% RJ (db/db + 1% P), db/db mice with 5% RJ (db/db + 5% RJ) (Figure A). Body weight of db/db mice was higher than that of db/db mice fed with RJ (Figure B). Moreover, glucose tolerance evaluated by iPGTT and ITT were improved by RJ (Figure C-F). Next, the expression of inflammation-related genes (Tnfa, Ifng) and nutrient transporter genes (Cd36, Sglt1, and Pept1) in small intestine were increased in db/db mice more than in db/m mice, nevertheless significantly decreased by RJ (Figure G-K). In the gut microbiota analyses by 16S rRNA sequencing, it was found that seven taxa, including Firmicutes, were overexpressed in db/db mice, while seven taxa including short-chain fatty acid-producing bacteria such as the family Ruminococcaceae, the genus Butyricioccus, and the genus Acetiviblio were overexpressed in db/db +5%RJ mice in the LEfSe algorithm (Figure L).
In summary, it is suggested that RJ might altere the gut microbiota and contributed to the improvement of metabolic disorders by changing the expression of genes related to nutrient absorption in the small intestine.

Disclosure
T. Okamura: Research Support; Yamada Bee Company, Inc. M. Hamaguchi: Research Support; Yamada Bee Company, Inc. H. Okamoto: Employee; Yamada Bee Company, Inc. N. Okumura: Employee; Yamada bee company, Inc. M. Fukui: None.
1627-P: Enhancer Regulator MLL4 Programs Skeletal Muscle Metabolic Efficiency by Limiting AMPK-Mediated Fuel Catabolism
Authors: YANG LIKUN , LIU LIN , DING CHENYUN , FU TINGTING , ZHOU ZHENG , GAN ZHENJI 
Published: June 2023

Skeletal muscle adapts to nutrient availability and physiological demands by fine-tuning gene expression patterns and metabolism to maximize metabolic efficiency. The mechanisms that enable and mediate muscle transcriptional and metabolic responses to environmental cues remain unclear, however. We have shown previously that enhancer regulator MLL4 is required for establishing and maintaining slow type I fiber program to ensure running endurance (J Clin Invest. 2020;130(9):4710-4725). Here, we report that MLL4 plays a critical role in directing muscle metabolic transcriptional adaptation that governs metabolic efficiency and systemic metabolism. MLL4 expression is regulated by nutrient availability, and skeletal muscle-specific ablation of MLL4 protects mice against diet-induced obesity and improves systemic glucose homeostasis despite reducing exercise endurance. Combining comprehensive metabolic and genomic analysis of the MLL4-depleted muscles using multidimensional ‘omics’ technologies, we gained insight into the molecular targets and biological functions of the MLL4 protein. Specifically, this seemingly paradoxical phenotype is due to markedly enhanced fuel catabolism in MLL4 deficient muscles, a favorable metabolic reprogramming caused by the activation of muscle AMPK. Isotopic 13C-glucose tracing experiments in myocyte provided further evidence that MLL4 exerts control upon muscle fuel catabolism. Remarkably, pharmacologic targeting the MLL4 pathway activates muscle AMPK, confers resistance to diet-induced obesity and ameliorates obesity-related insulin resistance and liver steatosis. These results identify an enhancer regulator limiting AMPK-mediated muscle fuel catabolism and offer a new potential therapeutic strategy for obesity-related metabolic disorders.

Disclosure
L.Yang: None. L.Liu: None. C.Ding: None. T.Fu: None. Z.Zhou: None. Z.Gan: None.
1636-P: The Effects of MS-275 Derivative in Diabetic Skeletal Muscle Atrophy
Authors: LEE NAMI , KIM YUJIN , CHOI SUJI , KIM YOUNGHA , SON YOUNGHO , CHOI SUNGE , KANG YUP Y. , YOUNG JEON JA , JIN HAN SEUNG , JIN KIM HAE , HO KIM TAE , AN SOYEON , LEE KWANWOO 
Published: June 2023

Aim/hypothesis: Histone Deacetylase (HDAC) is considered one of the pathogenic factors that induced muscle atrophy. MS-275, HDAC inhibitor, plays an important role in many physiological processes, and includes muscle contraction, mitochondrial metabolism, and decision of cell fate. Recently it was reported MS275 prevented insulin resistance and obesity. However, the effects of MS-275 derivative in diabetic skeletal muscle atrophy have not been well studied. In this study, we investigated the preventive effects of MS-275 derivative in diabetic muscle atrophy using db/db mice.
Method: To investigate the effects of MS-275 derivative on diabetic muscle atrophy, db/db mice were randomly divided into three groups: control group, db/db group, and db/db plus MS-275 derivative group. The mice were administered MS-275 derivative (7 mg/kg/i.p) for 4 weeks. The H&E stained sections were measured for cross-sectional area analyses using Image J software. To investigate the molecular mechanisms of MS-275 derivative, several factors related with muscle atrophy were tested using RT-PCR.
Results: Administration of MS-275 derivative to db/db mice suppressed muscle weight loss and insulin resistance. As a result of examining muscle mass and fat accumulation in the hindlimb by MRI, we found MS-275 derivative reduced fat accumulation and improved muscle loss. Tibialis anterior (TA) muscle and gastrocnemius (GA) muscle had significantly induced muscle atrophy in db/db mice. However, treatment with MS-275 derivative prevented weight loss of TA and GA muscles and it also recovered reduction of muscle fiber size. Interestingly, MS-275 derivative dramatically reduced atrophy related gene expressions in TA muscle.
Conclusion: In this study, MS-275 derivative ameliorated muscle atrophy through a reduction of atrophy related gene expressions in db/db mice. These results suggest MS-275 derivative may be a basis for the development of therapeutic drugs as applied to atrophy-related muscular or metabolic diseases.

Disclosure
N.Lee: None. H.Kim: None. T.Kim: None. S.An: None. K.Lee: None. Y.Kim: None. S.Choi: None. Y.Kim: None. Y.Son: None. S.Choi: None. Y.Y.Kang: None. J.Jeon: None. S.Han: None.
1649-P: Biased GLP-1 Improves Weight Loss with Additional Benefits on Glucose Homeostasis via Biased GIP in Diabetic Rodent Models
Authors: RODRIGUEZ RUBEN , TRACY TED , MORALES MARIKRIS , HERGARDEN ANNE , LAM DAVINA , KRISHNAN SHYAM , HANSEN STIG K. , CHAKRAVARTHY MANU 
Published: June 2023

GLP-1 and GIP when combined can deliver complementary pharmacology. CT-868 (CT) and CT-859 are biased dual GLP-1 and GIP receptor modulators with no β-arrestin coupling on either receptor. Effect of both compounds on weight loss (WL) and glucose (GLUC) homeostasis were assessed in relevant rodent models. At non-GIPR engaging doses in ob/ob mice, 30 nmol/kg CT achieved greater WL vs 200 nmol/kg Liraglutide (LI), an unbiased GLP-1RA (19.8% vs 11.5%, p=0.002), indicating biased GLP-1 improves WL vs unbiased GLP-1. GLUC tolerance test (GTT) in GIPR-/- mice showed similar reduction in AUCGLUC with LI and CT-859 at 20 nmol/kg 4h after dosing (53% vs 62%, p=NS), but only CT-859 maintained significant reduction after 24h and 48h, indicating biased GLP-1 induces a sustained GLUC lowering effect. After 14d of dosing in Akita mice with non-GIPR engaging doses of CT 20 nmol/kg, blood glucose (BG) decreased 30% vs LI 20 nmol/kg (p=0.01) indicating superior effect of biased GLP-1 on glycemic control. At GIPR engaging doses, CT 200 nmol/kg on background of insulin (INS) significantly lowered BG vs LI 200nmol/kg in Akita (↓35%, p=0.009) and DIO-STZ (↓32%, p&lt;0.0001) mice. Akita mice treated for 14d with CT 300 nmol/kg + low INS normalized BG to same extent as vehicle + high INS, but with 68% lower INS levels (p &lt; 0.0001). In GLP-1R-/- mice, CT 300 nmol/kg lowered AUCGLUC 38% vs vehicle (p&lt;0.0001) without concomitant INS excursion, showing that GIP enhances INS independent GLUC disposal or INS sensitivity. In response to pyruvate challenge, CT 100 nmol/kg suppressed AUCGLUC 36% (p&lt;0.05) and 14% (p=0.006) on a background of INS treatment in Akita and GLP-1R-/- mice, respectively, suggesting GIPR activation may contribute to suppression of endogenous GLUC production. Together, these data demonstrate that CT provides improved WL via biased GLP-1 with enhanced GLUC homeostasis via biased GIP relative to unbiased GLP-1 (LI). These findings have translated to T2D patients treated with CT-868.

Disclosure
R.Rodriguez: Employee; Carmot Therapeutics, Inc. T.Tracy: Employee; Carmot Therapeutics, Inc. M.Morales: None. A.Hergarden: Employee; Carmot Therapeutics, Inc. D.Lam: Employee; Carmot Therapeutics, Inc. S.Krishnan: Employee; Carmot Therapeutics, Inc. S.K.Hansen: Board Member; Carmot Therapeutics, Inc. M.Chakravarthy: Employee; Carmot Therapeutics, Inc.