bluuebunny/crossref_metadata_2025_split huggingface dataset:
191-LB: Artesunate Treatment Improves Hyperglycemia in a Rodent Model of Gestational Glucose Intolerance without Increasing Beta-Cell Mass
Authors: SZLAPINSKI SANDRA , HILL DAVID J. 
Published: June 2019

Gestational diabetes (GDM) has been associated with a failure to adequately increase maternal β-cell mass (BCM) during pregnancy. The anti-malarial drugs, artemisinins, have been shown to improve glucose homeostasis in rodent models of diabetes by increasing BCM. Our objective was to reverse BCM deficiency and impaired glucose tolerance in a mouse model of GDM using the artemisinin artesunate.
In order to produce glucose intolerance in pregnancy, female mice (F0) were fed a low protein (8%, LP) diet during gestation and lactation, and offspring weaned onto control (20%, C) diet. At 6-10 weeks age female offspring (F1) were time-mated and given C diet throughout pregnancy. Artesunate was administered via drinking water from gestational day (GD) 0.5-6.5. We previously found glucose intolerance, mimicking aspects of GDM, in LP-exposed offspring at GD18 when compared to animals fed a C diet. Thus, glucose tolerance tests (GTT) were performed at GD18 or for non-pregnant age-matched animals. Subsequently, pancreata were removed for fluorescence immunohistochemistry to assess histology.
Artesunate-treated LP females had a lower area under the curve during a GTT (389.9±52.3mmol/L*min) compared to non-treated LP females at GD18 (726.6±56.9mmol/L*min, p&lt;0.01). Furthermore, artesunate-treated LP females had improved glucose homeostasis at 5min (9.1 vs. 18.9mmol/L), 15min (11.6 vs. 20.9mmol/L) and 30min (10.2 vs. 19.2mmol/L) during the GTT compared to non-treated LP females at GD18 (p&lt;0.05). There were no significant differences in BCM, alpha-cell mass, or mean islet size between LP and artesunate-treated LP females at GD18.
The results show that artesunate-treated LP pregnant females had significantly improved glucose homeostasis compared to untreated LP mice at GD18. However, the improved glucose tolerance was not associated with increased BCM or changes in endocrine pancreas morphology.

Disclosure
S. Szlapinski: None. D.J. Hill: None.

Funding
St. Joseph's Health Care Foundation; Ontario Graduate Scholarship
1914-P: A Plant-Based Meal Increases Gastrointestinal Hormones and Satiety More Than an Energy- and Macronutrient-Matched Standard Meal in T2D, Obese, and Healthy Participants: A Three-Group Randomized Crossover Study
Authors: VELEBA JIRI , KLEMENTOVA MARTA , BELINOVA LENKA , HALUZIK MARTIN , PAVLOVICOVA RENATA , HILL MARTIN , PELIKANOVA TEREZIE , KAHLEOVA HANA 
Published: June 2019

Objective: Gastrointestinal hormones play a key role in glucose metabolism and satiety. We examined the acute effect of meal composition on these hormones in three population groups.
Research Design and Methods: A randomized crossover design was used to test the effects of two energy- and macronutrient-matched meals: a processed-meat (M-meal) and a vegan (V-meal) on gastrointestinal hormones, and satiety in participants with type 2 diabetes (T2D, n=20), obese participants (O, n=20), and healthy controls (H, n=20). Plasma concentrations of glucagon-like peptide -1 (GLP-1), amylin, and peptide YY (PYY) were determined at 0, 30, 60, 120 and 180 minutes. Satiety was assessed using a visual analogue scale. Repeated-measures ANOVA was used for statistical analysis.
Results: An increase in postprandial secretion of GLP-1 was observed after the V-meal in T2D (by 30.5%; 95% CI 21.2 to 40.7%; p&lt;0.001) and H (by 15.8%; 95% CI 8.6 to 23.5%; p=0.01). An increase in postprandial plasma concentrations of amylin was observed in all groups after the V-meal: by 15.7% in T2D (95% CI 11.8 to 19.6%; p&lt;0.001); by 11.5% in O (95% CI 7.8 to 15.3%; p=0.03); and by 13.8% in H (95% CI 8.4 to 19.5%; p&lt;0.001). An increase in postprandial values of PYY after the V-meal was significant only in H (by 18.9%; 95% CI 7.5 to 31.3%; p=0.03). The participants in all groups reported greater satiety after the V-meal: by 9.0% in T2D (95% CI 4.4 to 13.6%; p=0.004); by 18.7% in O (95% CI 12.8 to 24.6%; p&lt;0.001); and by 25.0% in H (95% CI 18.2 to 31.7%; p&lt;0.001).
Conclusions: Our results indicate there is an increase in gut hormones and satiety, following consumption of a single plant-based meal when compared with an energy- and macronutrient-matched standard meat meal.

Disclosure
J. Veleba: None. M. Klementova: None. L. Belinova: None. M. Haluzik: None. R. Pavlovicova: None. M. Hill: None. T. Pelikanova: None. H. Kahleova: None.

Funding
Ministry of Health of the Czech Republic (AZV15-27338A); Institute for Clinical and Experimental Medicine (MZCR00023001)
1929-P: Role of miR379 in Promoting Skeletal Muscle Atrophy in Type 1 Diabetes (T1D)
Authors: TUNDUGURU RAGADEEPTHI , KATO MITSUO , ABDOLLAHI MARYAM , LANTING LINDA L. , NATARAJAN RAMA 
Published: June 2019

T1D can lead to skeletal muscle atrophy which decreases quality of life and increases mortality. Non-coding RNAs such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are increasingly implicated in various pathological conditions. Recently, our lab demonstrated a unique megacluster of ∼ 40 miRNAs including miR379 and their host transcript lnc-MGC (a lncRNA) could induce early features of diabetic kidney disease. Based on new data showing that the expression of miR379 is increased in the atrophied skeletal muscle of T1D mice, in the current study, we investigated the in vivo role of miR379 in promoting skeletal muscle atrophy in vivo in T1D. We used miR379 knockout (KO) mice generated by CRISPR-Cas9 technology. C57BL/6 (WT) and miR379 KO male mice were injected with streptozotocin (STZ 50mg/kg) for 5 consecutive days to induce T1D. miR379 target genes and muscle atrophy markers in the skeletal muscle were analyzed using qPCR. Body composition analysis was performed using Echo-MRI. Fasting blood glucose levels one week after diabetes development, were significantly lower in in miR379 KO mice compared to WT-mice. Moreover, miR379 KO mice showed significant protection from T1D-associated loss in body weight, muscle and fat mass relative to WT mice. Toward interrogating the underlying mechanism, the expression of atrophy-associated genes and miR379 target genes were assessed in skeletal muscle samples. In WT mice, T1D increased the expression of muscle atrophy-associated genes (myostatin and Atrogin1), and decreased FIS1 and EDEM3, miR379 target proteins involved in regulation of mitochondrial health and ER stress respectively. Intriguingly, miR379 KO mice depicted significant protection from these T1D-induced changes. These results suggest miR-379 promotes skeletal muscle atrophy in T1D via upregulating genes involved in muscle wasting and downregulating genes involved in mitochondrial health, thus uncovering novel non-coding RNA dependent mechanisms of skeletal muscle dysfunction in T1D.

Disclosure
R. Tunduguru: None. M. Kato: None. M. Abdollahi: None. L.L. Lanting: None. R. Natarajan: None.

Funding
National Institutes of Health
193-OR: Glycemic Control via Glucagon Modulation by a Novel Brown Adipose Peptide Hormone
Authors: PISTON DAVID W. , USTIONE ALESSANDRO , GUNAWARDANA SUBHADRA C. , HUGHES JING 
Published: June 2019

Subcutaneous transplants of embryonic brown adipose tissue (BAT) lead to euglycemia without insulin in mouse models of T1D [Diabetes 2012 61:674]. Euglycemia is accompanied by normalized plasma glucagon levels, restored healthy white adipose tissue, reduced inflammatory cytokines, and increased anti-inflammatory adipokines. Elevated IGF-1 was shown to play a role in successful transplants, putatively by direct stimulation of the insulin receptor [Am. J. Physiol. Endocrinol. Metab. 2015 308:E1043]. However, the mechanism underlying this effect remained unknown. We hypothesized that a secreted product from the transplanted BAT communicates with the recipient allowing a new metabolic equilibrium in the absence of insulin. We tested this using buffer conditioned by cultured immortalized BAT cells. We injected this buffer into diabetic NOD mice once daily for 7 consecutive days. In 5 of the 9 animals studied, blood glucose levels dropped back to the normal range (∼150 mg/dl) for at least 2 months with one animal remaining euglycemic for 5 months with no further intervention. As in embryonic BAT transplants, conditioned buffer injections led to a rapid decrease in plasma glucagon. We found that applying this conditioned buffer to isolated mouse and human islets lowers glucagon secretion directly (without significant changes in insulin or somatostatin). To purify and identify the active BAT-secreted compound, we established a multi-step fractionation protocol using size exclusion, ion exchange, and hydrophobicity columns to concentrate the active compound ∼10 million-fold over the initial BAT-conditioned buffer. Protease, denaturation, and spectroscopy experiments revealed a modified peptide of ∼1600 Da. Initial screening of GPCR targets [Nat Struct Mol Biol. 2015 22:362] revealed binding to the μ-opioid receptor, which is expressed preferentially in α-cells within the islet of Langerhans. Thus, these data suggest a novel path towards clinical antagonism of glucagon secretion.

Disclosure
D.W. Piston: Consultant; Self; Pfizer Inc. A. Ustione: None. S.C. Gunawardana: None. J. Hughes: None.

Funding
National Institutes of Health (DK098659); The Leona M. and Harry B. Helmsley Charitable Trust
1935-P: Decoupling between ATP Utilization and Replenishment in Insulin Resistant Skeletal Muscle
Authors: VASQUEZ JUAN A. , SOLIS-HERRERA CAROLINA , TRIPATHY DEVJIT , ABDUL-GHANI MUHAMMAD , DEFRONZO RALPH A. , CLARKE GEOFFREY D. 
Published: June 2019

For optimal energy utilization, depletion and recovery of phosphocreatine (PCr) during exercise must be tightly coupled.
Aim: To measure metabolites in vastus lateralis (VL) muscle of normal glucose tolerant (NGT) and type 2 diabetes mellitus (T2DM) subjects by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) during and following exercise. Matsuda index (MI) of insulin sensitivity, fasting plasma glucose (FPG), intramyocellular lipid concentration [IMCL], and mitochondrial density (MitoD) were also measured.
Methods: 12 NGT (age=50±11y; A1c=5.6±0.3%; BMI=28.5±4.1kg/m-2) and 10 T2DM (age=53±10y; A1c=7.5±0.8%; BMI=30.4±4.6kg/m-2) subjects received an OGTT to determine MI. [IMCL] in VL was quantified by 1H-MRS. In 15 subjects (7 T2DM, 8 NGT) MitD was determined by electron microscopy.
Results: The PCr recovery time constant (k) was lower in T2DM (0.01±0.004 vs. 0.02±0.01 s-1; p=0.05). Baseline [PCr] (25.3±3.0 vs. 28.5±3.3 mM; p=0.03) and average [PCr] over the last minute of exercise (14.5±4.7 vs. 20.9±4.7 mM; p&lt;0.05) were lower in T2DM. PCr percent decrease, (%Δ), was negatively correlated with PCr recovery halftime, t (ρ=0.77; p&lt;0.05). The initial rate of PCr depletion and initial rate of PCr recovery were correlated in NGT (r=0.83; p&lt;0.05) but not in T2DM subjects (r=0.30; p=0.39). FPG negatively correlated with baseline [PCr] (ρ=-0.63; p&lt;0.05) and MI negatively correlated with %Δ (ρ=-0.50; p&lt;0.05) in all subjects. [IMCL] was increased in T2DM (6.9±1.2 vs. 9.1±1.4; p&lt;0.05) and correlated negatively with t (ρ=0.47; p=0.03). MitoD in T2DM subjects correlated with k (r=0.76; p&lt;0.05).
Conclusion: These data suggest a disruption in the regulation of energy utilization and production of ATP and PCr, which may be due to reduced mitochondrial density and/or altered substrate dynamics in T2DM skeletal muscle.

Disclosure
J.A. Vasquez: None. C. Solis-Herrera: Advisory Panel; Self; Sanofi. D. Tripathy: None. M. Abdul-Ghani: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. G.D. Clarke: None.

Funding
National Institutes of Health (DK-24092-34 to R.A.D), (K25-DK-089012 to G.D.C.)
1949-P: Elevated FGF-21 during Circadian Misalignment in Healthy Humans
Authors: BROUSSARD JOSIANE L. , MORTON SARAH J. , MARKAN KATHLEEN , MCHILL ANDREW W. , HIGGINS JANINE , MELANSON EDWARD , WRIGHT KENNETH 
Published: June 2019

Circadian misalignment—sleeping during the biological day and eating at a time when the internal circadian clock promotes sleep—is a risk factor for obesity and diabetes, implicating circadian misalignment as a metabolic stressor. Fibroblast growth factor 21 (FGF-21) is a hepatokine secreted in response to stress and found to be elevated in human obesity and diabetes. Activation of peroxisome proliferator-activator receptor alpha by free fatty acids (FFA), can induce the expression of FGF-21 expression. It has been previously reported that circadian misalignment results in elevated fasting FFA. However, the impact of circadian misalignment on FGF-21 has not been explored.
Fourteen healthy adults (6M; aged 26.4±1.2y, BMI 22.7±0.5 kg/m2; mean±SD) participated in a simulated shift-work protocol using a consecutive study design to examine the impact of circadian misalignment on diabetes- and obesity-related risk factors. Participants were provided with a 3d energy balance diet prior to admission and during the 5d inpatient study. Identical meals were consumed each day to minimize the effects of dietary intake on metabolic hormones. Blood was sampled every 1-2 hours for 24 hours during circadian alignment and circadian misalignment and assayed for melatonin and FGF-21.
The melatonin rhythm was used as a marker of the master circadian clock and was unchanged during simulated shift-work, indicating circadian misalignment. Circadian misalignment led to elevated FGF-21 during scheduled wake (+123±41% mean±SEM; p&lt;0.01) and across 24h (+36±16%; p&lt;0.05) relative to circadian alignment.
Circadian misalignment triggers a stress response that includes an increase in circulating FGF-21. The physiological implications of acute elevations in FGF-21 are unknown, and may contribute to metabolic dysregulation associated with circadian misalignment.

Disclosure
J.L. Broussard: Advisory Panel; Self; National Institutes of Health. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Sleep Research Society, Society in Science-The Branco Weiss Fellowship. S.J. Morton: None. K. Markan: None. A.W. McHill: None. J. Higgins: None. E. Melanson: None. K. Wright: Advisory Panel; Self; National Institutes of Health, Torvec, Inc. Research Support; Self; National Institutes of Health, Office of Naval Research, Pacific-12 Conference, SomaLogic, Inc. Other Relationship; Self; Circadian Therapeutics, Inc., Kellogg Company, Torvec, Inc.

Funding
National Institutes of Health (UL1RR025780, P30DK048520); Sleep Research Society Foundation; Branco Weiss Fellowship Society in Science (K01DK110138, R21DK092624)
1954-P: Combined Treatment with Exendin-4 and Metformin Attenuates Breast Cancer Growth
Authors: FUJIMURA YUKI , NOMIYAMA TAKASHI , IWAYA CHIKAYO , KAWANAMI TAKAKO , HAMAGUCHI YURIKO , TANAKA TOMOKO , YANASE TOSHIHIKO 
Published: June 2019

Cancer is a major cause of death in patients with diabetes. Incretin therapy has received much attention, because of its tissue protective effects beyond glycemic control. We have previously reported anti-prostate cancer effect of Ex-4 and metformin (Diabetes 2014, PLOS ONE 2015). In addition, we have recently reported that Ex-4 attenuates breast cancer growth (Endocrinology 2017). Then, we next examined the effect of combined treatment of Ex-4 with Metformin in breast cancer. In human breast cancer cell lines, MCF-7, MDA-MB-231 and KPL-1 cells, Ex-4 or metformin reduced cell number in a dose-dependent manner. Further, combined treatment of Metformin and Ex-4 additively attenuated the growth curve progression of breast cancer cells. In BrdU assay, Ex-4 or Metformin significantly decreased breast cancer cell proliferation, and further reduction of BrdU incorporation was observed by combined treatment with Ex-4 and Metformin, suggesting that Ex-4 and Metformin additively decreased DNA synthesis in breast cancer cells. Although apoptotic cells were not observed in Ex-4 treated breast cancer cells, apoptotic cells were clearly detected in metformin treated breast cancer cells in TUNEL assay. Further, the experiments using xenograft model mice transplanting MCF-7 cells into athymic mice revealed that Ex-4 and metformin additively attenuated breast cancer growth in vivo also. These data suggest that Ex-4 and metformin attenuates breast cancer cell proliferation and metformin induces apoptosis in breast cancer cells and combined treatment with Ex-4 and metformin could be an optional therapy to inhibit breast cancer progression.

Disclosure
Y. Fujimura: None. T. Nomiyama: None. C. Iwaya: None. T. Kawanami: None. Y. Hamaguchi: None. T. Tanaka: None. T. Yanase: None.
1955-P: GLP-1R Activation Attenuates Prostate Cancer Growth via Inhibiting Cell Cycle Progression
Authors: SHIGEOKA TORU , NOMIYAMA TAKASHI , KAWANAMI TAKAKO , HAMAGUCHI YURIKO , TANAKA TOMOKO , IRIE SHINICHIRO , NABESHIMA KAZUKI , TANAKA MASATOSHI , YANASE TOSHIHIKO 
Published: June 2019

Incretin therapy is one of the most popular treatment for type 2 diabetes. We have previously reported anti-prostate cancer effect of GLP-1R agonist Exendin-4(Ex-4) (Diabetes 2014, PLOS ONE 2015), and LEADER trial suggested that GLP-1R agonist could reduce prostate cancer. In our previous report, the attenuation of prostate cancer cell proliferation was depending on GLP-1R expression, and Ex-4 did not attenuate cell proliferation in ALVA-41, a prostate cancer cell without intrinsic GLP-1R expression. Then, we next examined anti-prostate cancer effect in ALVA-41 forced expressed GLP-1R using lentivirus vector (ALVA-41-GLP-1R). We confirmed abundant GLP-1R expression in ALVA-41-GLP-1R using RT-PCR and immunohistochemistry, and intracellular cAMP level was increased by Ex-4 in ALVA-41-GLP-1R. Ex-4 significantly decreased the proliferation of ALVA-41-GLP-1R in a dose dependent manner, but not in ALVA-41-control. BrdU assay revealed that DNA synthesis was attenuated in ALVA-41-GLP-1R, and G1 to S phase entry was inhibited in cell cycle distribution in flow cytometry analysis. Further, p27kip protein was increased and Skp2, ubiquitin ligase for p27kip, expression was decreased in ALVA-41-GLP-1R treated by Ex-4. In vivo experiments using xenograft model mice transplanting ALVA-41-GLP-1R revealed that Ex-4 decreased prostate cancer growth via activation of GLP-1R forced expressed in ALVA41. Further, GLP-1R expression level in human prostate cancer tissues was inversely associated with Gleason grading system of human prostate cancer. These data suggested that forced expressed GLP-1R attenuated prostate cancer cell proliferation via inhibiting cell cycle progression in vivo and in vitro, and GLP-1R activation could be one of optional therapy for prostate cancer.

Disclosure
T. Shigeoka: None. T. Nomiyama: None. T. Kawanami: None. Y. Hamaguchi: None. T. Tanaka: None. S. Irie: None. K. Nabeshima: None. M. Tanaka: None. T. Yanase: None.

Funding
Japan Society for the Promotion of Science
1960-P: Comparative Effects of TNFα and IL-6 Inhibitors on Glucose and Lipid Metabolism in Patients with Rheumatoid Arthritis (RA)
Authors: ISHIZUKA TATSUO , FUJIOKA KEI , MORI ICHIRO , TAKEDA TOMOFUMI , INUI SAORI 
Published: June 2019

Association between TNFα and IL-6 and glucose tolerance has been reported. However, it is not clear that TNFα and IL-6 affect on glucose tolerance. Recently, biologic agents such as TNF and IL-6 inhibitors have been appeared in the treatment of RA. We have examined comparative effects of TNF αand IL-6 inhibitors on glucose tolerance and lipid metabolism in patients with rheumatoid arthritis. Registered 589 patients with RA have been screened by HbA1c level (more than 5.6%), treatment with methotrexate (MTX) and treatment with biologic agents with or without MTX. We have excluded the patients with RA who are treated with insulin, and selected 30 cases of RA patients who were able to follow-up for 12 months (M). Patients with RA were divided to 3 groups by the treatments as follows: TNF inhibitors with MTX (TNF+MTX), IL-6 with and without MTX (IL-6±MTX) and MTX alone. Body weight, HbA1c, LDL-C, HDL-C, LDL-C/HDLC(L/H) and disease activity score (DAS) were measured before and after 6 and 12 M. There were no differences of DAS between each group before and after 6 and 12 M. DAS in each group was a significantly decreased compared with before (P &lt; 0.05-0.001). HbA1c levels in TNF+MTX were not significantly different (before 6.08%, 6 M 5.92%, 12M 5.91%), but those in MTX alone and IL-6±MTX were significantly improved (before 6.42% and 6.2%, 6M 5.87% and 5.78%, P&lt; 0.05, 12M 5.82%, P&lt; 0.05 and 5.81%, P&lt; 0.01), respectively. There were no significant differences of body weight between each group. HDL-C and LDL-C in IL-6±MTX were significantly (P&lt; 0.01) increased (before 58.2 mg/dl and 123.2 mg/dl, 6M 71.7 mg/dl and 148.5 mg/dl, 12M 63.4 mg/dl and 144.2 mg/dl), respectively. L/H in TNF+MTX was significantly (P&lt;0.05) decreased.
In conclusion, effect of glucose tolerance in IL-6 inhibitors was better than TNF inhibitors in RA patients with glucose intolerance. However, TNF inhibitor in lipid metabolism was better than IL-6 inhibitors.

Disclosure
T. Ishizuka: None. K. Fujioka: None. I. Mori: None. T. Takeda: None. S. Inui: None.
1964-P: Type 1 Diabetes: Sclerostin Resistance Improves Glucose Metabolism and Protects Bone Mass
Authors: LEANZA GIULIA , ALIPPE YAEL , LEE SEUNG-YON , STROLLO ROCKY , POZZILLI PAOLO , CIVITELLI ROBERTO , NAPOLI NICOLA 
Published: June 2019

Type 1 diabetes (T1D) is characterized by metabolic abnormalities and bone fragility. In humans and preclinical models of T1D, serum markers of bone formation are decreased suggesting reduced bone turnover rates. Moreover, circulating levels of the Wnt inhibitor sclerostin (Scl) are higher in T1D patients. To test the role of Scl in T1D bone disease, we introduced the Scl-resistant Lrp5A214V mutation, associated with high bone mass (HBM), in mice carrying the Ins2Akita mutation (Akita), which causes hypoinsulinemia and hyperglycemia at age 4-5 weeks. Although both Akita and Akita/HBM mutants developed diabetes (non-fasting blood glucose ≥300 mg/dl), they showed a very different onset timing. At 6 weeks, only 30% of Akita/HBM mice developed hyperglycemia, compared to 90% of Akita mice (n=10), with the majority of Akita/HBM mice becoming hyperglycemic by 12 weeks. At 6 weeks, Akita mice showed a significant impairment in glucose tolerance in an intraperitoneal glucose tolerance test (ipGTT) relative to mild glucose intolerance demonstrated in Akita/HBM mice (p&lt;0.05 for difference in AUC; n=5-7). No differences in serum insulin, glucagon and C-peptide were found between Akita/HBM and Akita mice at time 0 and 30 minutes during the ipGTT (n=2-6). Importantly however, Akita/HBM showed a significant improvement in insulin sensitivity in an ip insulin tolerance test relative to Akita mice at 7 weeks of age, which persisted until 30 weeks (p&lt;0.05 for difference in AUC; n= 4-7). Strikingly, bone mass was 18% higher in Akita/HBM relative to Akita littermates at 12 weeks (p&lt;0.001; n=3-6), a difference that persisted up until at least 18 weeks of age, despite the prolonged hyperglycemia. Together, these results suggest that Scl resistance may improve peripheral glucose metabolism and slow down the onset of T1D, although it does not prevent it. Even though we have not yet measured bone strength, Wnt stimulation protects bone mass and may delay the onset of metabolic abnormalities seen in T1D.

Disclosure
G. Leanza: None. Y. Alippe: None. S. Lee: None. R. Strollo: None. P. Pozzilli: None. R. Civitelli: Stock/Shareholder; Self; Amgen Inc., Eli Lilly and Company, Merck & Co., Inc. N. Napoli: None.