bluuebunny/crossref_metadata_2025_split huggingface dataset:
1800-P: Transcriptomic Evidence of a Role for Neuron-Glia Interactions in Diabetes Remission Induced by the Central Action of Fibroblast Growth Factor 1 (FGF-1)
Authors: BENTSEN MARIE A. , RAUSCH DYLAN , MIRZADEH ZAMAN , SCARLETT JARRAD , BROWN JENNY M. , ALONGE KIMBERLY M. , MEEK THOMAS H. , SECHER ANNA , JORGENSEN RASMUS , PERS TUNE , SCHWARTZ MICHAEL W. 
Published: June 2019

Lasting remission of hyperglycemia can be achieved in rodent models of type 2 diabetes by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF-1), and the mediobasal hypothalamus (MBH) was recently identified as a target for this effect. To investigate the cellular basis of FGF-1 action in the MBH, we combined whole tissue RNA-sequencing with large-scale single cell and single nuclei RNA-sequencing to generate &gt;60,000 single cell transcriptomes from diabetic ob/ob mice harvested 5d after a single icv injection of either FGF-1 or vehicle. Of the 4 known FGF receptor genes, 3 were expressed in the MBH, primarily by glial cells rather than neurons. Employing weighted gene co-expression network analysis, distinct modules that correlated with icv FGF-1 treatment were identified, again primarily in glial cells. In astrocytes, the response to FGF-1 closely paralleled the neuroprotective “A2” transcriptional phenotype induced by stroke, and both the proportion of differentiating oligodendrocytes and genes involved in extracellular matrix remodeling of the perivascular space were also upregulated by FGF-1. By comparison, the neuronal response to icv FGF-1 was one of generalized inhibition, including decreased expression of Agrp and Pmch (encoding agouti-related peptide and pro-melanin-concentrating hormone (MCH), respectively). Since Agrp and MCH neurons are activated in ob/ob mice, and since this effect predisposes to hyperglycemia, these findings support a model in which sustained inhibition of these and perhaps other neuronal subsets underlies diabetes remission induced by icv FGF-1. Moreover, this neuronal inhibition appears to be driven by neuroprotective glial responses elicited by FGF-1. These data add to growing evidence of a crucial role for neuron-glia interactions in hypothalamic control of glucose homeostasis.

Disclosure
M.A. Bentsen: None. D. Rausch: None. Z. Mirzadeh: Consultant; Self; Novo Nordisk A/S. J. Scarlett: None. J.M. Brown: None. K.M. Alonge: Research Support; Self; Novo Nordisk Inc. T.H. Meek: Employee; Self; Novo Nordisk Inc. A. Secher: Employee; Spouse/Partner; Gubra. Employee; Self; Novo Nordisk A/S. Speaker's Bureau; Spouse/Partner; Gubra. Stock/Shareholder; Self; Novo Nordisk A/S. R. Jorgensen: Employee; Self; Novo Nordisk A/S. T. Pers: None. M.W. Schwartz: Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S.

Funding
National Institutes of Health; Novo Nordisk Foundation; Lundbeck Foundation; Novo Nordisk A/S
1801-P: Common Hepatic Artery Denervation Does Not Alter the Counterregulatory Response to Hypoglycemia in an Insulin Resistant Canine Model
Authors: KRAFT GUILLAUME , MOORE L. MERKLE , FARMER BEN , SCOTT MELANIE F. , EDGERTON DALE S. , WILLIAMS PHILLIP E. , AZAMIAN BOBAK , CHERRINGTON ALAN D. 
Published: June 2019

With the recent interest in sympathetic modulation as a way to improve insulin sensitivity and insulin secretion, it is important to assess the safety of the procedure. Five dogs were fed a high fat high fructose diet for 5-week before undergoing a hyperinsulinemic hypoglycemic clamp (insulin infused IV at a rate of 1.5 mU/kg/min). Then the dogs underwent a common hepatic artery surgical denervation (CHAD n=5) and were studied 1, 2 and 3 months post-surgery with the same hypoglycemic challenge. At the end of the protocol, the norepinephrine content in the liver (7±3 ng/g) and pancreas (91±34 ng/g) were significantly lower than levels in the livers and pancreas of 4 sham denervated animals (460±100 and 590±93 ng/g respectively), indicating successful denervation. There were no significant differences in fasting insulin, glucose or glucagon concentrations over the 3 months (see Table). The insulin and glucose concentrations during the last 90 min of the hypoglycemic challenge prior to and post-CHAD were also not different. The peak in plasma glucagon and epinephrine levels occurred at 30 and 120 min respectively and were similar in magnitude pre- and post-CHAD. Four sham denervated animals had the same response to the insulin induced hypoglycemic challenge as CHAD dogs.
In conclusion, the response to hypoglycemia was not affected by sympathetic denervation of the common hepatic artery.

Disclosure
G. Kraft: Consultant; Self; Metavention. L. Moore: None. B. Farmer: None. M.F. Scott: None. D.S. Edgerton: Speaker's Bureau; Self; Novo Nordisk A/S. P.E. Williams: None. B. Azamian: Employee; Self; Metavention. A.D. Cherrington: Board Member; Self; Biocon, Fractyl Laboratories, Inc., Metavention, Sensulin, LLC., vTv Therapeutics, Zafgen, Inc. Consultant; Self; Abvance, Boston Scientific Corporation, California Institute for Biomedical Research, Galvani Bioelectronics Limited, MedImmune, Novo Nordisk Inc., Thetis Pharmaceuticals LLC. Research Support; Self; Abvance, Diasome Pharmaceuticals, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; Abvance, Biocon, Fractyl Laboratories, Inc., Metavention, Novo Nordisk Inc., Sensulin, LLC., Thetis Pharmaceuticals LLC, Zafgen, Inc.

Funding
Metavention, Inc.
1802-P: Nr1d1/Nr1d2 in POMC Neurons Regulates Circadian Eating Behaviors and Energy Expenditure
Authors: ZHOU WENJUN , YANG TINGTING , LI XIN , SUN ZHENG 
Published: June 2019

Proopiomelanocortin (POMC) neurons in the arcuate nucleus of ventral hypothalamus and the nucleus tractus solitarius are involved in many biological functions. Nuclear receptor Nr1d1 and Nr1d2 are the key component of the molecular circadian clock machinery and are widely expressed in the brain. Here we address the role of Nr1d1/Nr1d2 in POMC neurons using conditional knockout mouse models. Mice with Nr1d1 and Nr1d2 specifically depleted in POMC neurons (KO) displayed a diet-dependent metabolic dysregulation. When fed with normal chow, KO mice show similar body weight, food intake, and energy expenditure as control WT mice. However, KO mice are resistant to high-fat diet (HFD)- induced obesity even though they consume slightly more food. Energy expenditure and the temporal pattern of food intake was altered in the KO mice fed with HFD when compared to control. These findings revealed the pivotal role of Nr1d1 and Nr1d2 of the POMC neurons in regulating the eating behavior and energy expenditure.

Disclosure
W. Zhou: None. T. Yang: None. X. Li: None. Z. Sun: None.

Funding
American Diabetes Association (1-19-PDF-012 to W.Z.)
1810-P: Effect of HM15211, a Novel Long-Acting GLP-1/GIP/Glucagon Triple Agonist in the Neurodegenerative Disease Models
Authors: WONKI KIM , KIM JEONG A. , LEE SANG HYUN , BAE SUNGMIN , CHOI IN YOUNG , KIM YOUNG HOON 
Published: June 2019

Metabolic disturbances such as diabetes and obesity, are a potential risk factors for progressive neurodegenerative disease such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and multiple sclerosis (MS). There is evidence that an antidiabetic or obesity drug of the glucagon-likepeptide-1(GLP-1) family has direct neuroprotective effects in an experimental models of neurodegenerative disease. Recently, we have developed HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist. Previous studies have shown that HM15211 with a unique activity profile exerted neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced subchronic PD mice model. In the present study, we evaluated 1) the neuroprotective effects of HM15211 in chronic MPTP/probenecid PD model, 2) the protection of AD progression in diabetic model, and 3) neuroprotective effect in the relapsing-remitting experimental autoimmune encephalomyelitis (EAE) model of MS. In chronic PD mice model, HM15211 administration protected dopaminergic neuronal death and decreased alpha synuclein in striatum. HM15211 also significantly improved the MPTP/probenecid induced motor impairments in behavior tests. In addition, HM15211 increased phosphorylated tau, and reversed inflammatory cytokines and oxidative stress marker in aged db/db mice, which have a pathological characters of AD. These results suggest that HM15211 have a protective effect in progression from diabetes to AD. In another experiment, HM15211 have shown the anti-inflammatory and neuroprotective effects in the EAE mouse model. HM15211 significantly reduced the EAE clinical score and resulted in the reversal of histopathological sequelae compared to vehicle. Furthermore, HM15211 decreased pro-inflammatory cytokines, while it upregulated anti-inflammatory cytokines. Based on these observations, HM15211 might be a potential therapeutic option for the neurodegenerative diseases.

Disclosure
K. Wonki: Employee; Self; Hanmi Pharm. Co., Ltd. J.A. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. S. Lee: Employee; Self; Hanmi Pharm. Co., Ltd. S. Bae: None. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. Y. Kim: None.
1814-P: Type 2 Diabetes Increases Stroke Severity through Sustained Hyperperfusion of Cerebral Vasculature following Ischemic Stroke in Rats
Authors: RAMSAY CIARAN DAVID , HOWELLS DAVID W. , KESKE MICHELLE , SUTHERLAND BRAD , PREMILOVAC DINO 
Published: June 2019

Stroke is a leading cause of death and permanent disability. Type 2 diabetes (T2D) increases the incidence of stroke by four-fold and is a strong predictor of worse outcome following stroke with greater disability and mortality than in nondiabetics. While the reasons for increased stroke severity in T2D are unclear, we hypothesized that T2D alters the cerebral vascular response to ischemic stroke leading to reduced vascular reperfusion and hence greater infarct following restoration of blood flow post-stroke. To address this hypothesis, 15-week-old male Sprague Dawley rats were given a high fat diet and treated with osmotic-mini pump infused STZ (110mg/kg over 14 days) to develop a mild T2D phenotype, characterized by obesity and glucose of 8-10mM. Normal chow-fed aged matched rats were used as controls. Four weeks after induction of T2D, we quantified cerebral perfusion in real-time using contrast enhanced ultrasound (CEU) before, during and immediately after middle cerebral artery occlusion, the gold standard model of ischemic stroke. Following this, rats were allowed to recover and a battery of behavioral tests was used to assess stroke severity over 14 days. A final CEU measure was obtained 14 days post-stroke to track vascular changes over time. Cerebral perfusion tended to be increased in T2D rats at baseline but was similarly reduced during middle cerebral artery occlusion. Strikingly, T2D rats had a 3-fold increase in cerebral perfusion immediately post-stroke and this hyperperfusion was sustained 14 days post-stroke. Importantly, although there was no difference in behavior at baseline or immediately following stroke, by day 6, T2D rats developed a greater level of disability compared with control rats that was sustained until day 14.
In conclusion, we demonstrate that T2D alters the cerebral vascular response to ischemic stroke, leading to severe vascular hyperperfusion and that this is associated with a greater level of disability in rats.

Disclosure
C.D. Ramsay: None. D.W. Howells: None. M. Keske: None. B. Sutherland: None. D. Premilovac: None.
182-LB: Circulating Adhesion Molecules and Relationships to Micro and Macrovascular Outcomes: The TODAY Study
Authors: TRYGGESTAD JEANIE B. , SHAH RACHANA , BRAFFETT BARBARA , BACHA FIDA , GIDDING SAMUEL , GUBITOSI-KLUG ROSE , SHAH AMY SANGHAVI , URBINA ELAINE M. , KATZ LORRAINE E. 
Published: June 2019

Atherosclerosis begins in childhood, accelerating in those with obesity, hypertension and type 2 diabetes (T2DM). Binding of mononuclear cells to vascular endothelium, initiated by cellular adhesion molecules and chemokines, is an early step in this process. The TODAY study, a clinical trial of adolescents with T2DM, included three treatment arms. The primary end-point was treatment failure defined as A1c persistently &gt;=8% over 6 months period or metabolic decompensation. The aims of the present analysis are to evaluate: 1) changes in ICAM, VCAM, E-Selectin and MCP-1 over time 2) whether treatment group influences levels of these biomarkers and 3) the association of these markers with macrovascular and microvascular outcomes. Participants from the TODAY cohort (n=515) with at least two of the four annual assessments of adhesion molecules at baseline, 12, 24, 36 months were included. Over the study period, there were significant increases in ICAM (p=0.002) and MCP-1 (p&lt;0.001) and significant decreases in VCAM (p&lt;0.001) and E-Selectin (p=0.016) across the entire cohort. There were no significant treatment group interactions. Participants who reached the primary outcome had higher E-Selectin compared to participants with sustained control over the duration of the study (p&lt;0.0001). ICAM increased 2.0% (p&lt;0.001), VCAM increased 1.5% (p&lt;0.001), E-selectin increased 7.0% (p&lt;0.001), and MCP-1 increased 1.4% (p=0.001) for every 1% increase in HbA1c. E-selectin was 9.5% (p&lt;0.001) and 5.2% (p=0.017) higher and ICAM was 5.9% (p=0.001) and 4.5% (p=0.046) higher in participants with microalbuminuria or hyperfiltration respectively. E-selectin increased with increasing left ventricular mass and TAPSE, a measure of right ventricular function, (p=0.043 and p=0.001, respectively). This analysis demonstrates cellular adhesion molecules increase with increasing HbA1c in youth with T2DM, and ICAM and E-selectin are associated with worsening micro and macrovascular outcomes.

Disclosure
J.B. Tryggestad: None. R. Shah: None. B. Braffett: None. F. Bacha: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Pediatric Diabetes Consortium. Other Relationship; Self; AstraZeneca, Jaeb Center for Health Research. S. Gidding: Research Support; Self; Color Genomics. R. Gubitosi-Klug: None. E.M. Urbina: None. L.E. Katz: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
1829-P: Acute Inhibition of Intestinal Neprilysin Enhances Glucose-Stimulated Insulin Secretion in Mice
Authors: ESSER NATHALIE , MUNDINGER THOMAS O. , BARROW BREANNE , MONGOVIN STEVE M. , ZRAIKA SAKENEH 
Published: June 2019

Increased activity of the ubiquitous peptidase neprilysin in obesity and type 2 diabetes (T2D) is associated with impaired glucose homeostasis, and its inhibition has been shown to improve β-cell function. Neprilysin cleaves and inactivates insulinotropic peptides, including some produced in the intestine (e.g., GLP-1, GIP, CCK). While neprilysin is expressed in the intestine, the contribution of intestinal neprilysin to modulate β-cell function remains unknown. Thus, we sought to determine whether acute selective pharmacological inhibition of intestinal neprilysin enhances glucose-stimulated insulin secretion (GSIS) in healthy mice and could be a therapeutic target in T2D. High (20 mg/kg) or low (0.05 mg/kg) dose neprilysin inhibitor thiorphan, or vehicle, was orally administered to chow-fed C57BL/6 mice, then plasma and tissues were collected after 40 minutes to determine neprilysin activity. High dose thiorphan significantly inhibited neprilysin activity in plasma and all tissues listed below (data not shown). In contrast, low dose thiorphan inhibited neprilysin activity by 91±5% in colon, 50±12% in ileum and 62±4% in jejunum vs. vehicle (n=7-8, p&lt;0.05), without altering neprilysin activity in pancreas, kidney and plasma. Thus, low dose thiorphan was used to selectively inhibit intestinal neprilysin in a separate cohort of mice 30 minutes prior to an oral glucose tolerance test (OGTT; 2g/kg glucose) in which GSIS was determined. Compared to vehicle, thiorphan significantly increased insulin levels during the OGTT (incremental AUC 0-30 minutes: 3181±606 vs. 5786±600 pmol/L.minutes-1, n=6-7, p=0.01) without altering basal insulin (95±21 vs. 114±25 pM, n=6-7, p=0.6).
In summary, under physiological conditions, acute selective inhibition of intestinal neprilysin increases GSIS in vivo. Thus, intestinal neprilysin plays a role in modulating β-cell function, and strategies to inhibit neprilysin specifically in the intestine might improve β-cell dysfunction in T2D.

Disclosure
N. Esser: None. T.O. Mundinger: None. B. Barrow: None. S.M. Mongovin: None. S. Zraika: Research Support; Self; Novartis Pharmaceuticals Corporation.

Funding
National Institutes of Health (DK098506); Belgian American Educational Foundation; Société Francophone du Diabète
1831-P: Delayed Glucagon Suppression Contributes to Postprandial Hyperglycemia Independently of the Degree of Insulin Secretion
Authors: ADAMS J.D. , LAURENTI MARCELLO C. , RIZZA ROBERT A. , EGAN AOIFE M. , COBELLI CLAUDIO , MAN CHIARA DALLA , VELLA ADRIAN 
Published: June 2019

Type 2 diabetes (T2DM) is characterized by impaired postprandial insulin secretion and glucagon suppression. Recent work suggests that α-cell dysfunction is independent of β-cell dysfunction. The effect of diabetes-associated variation in TCF7L2 on α-cell function also suggests a direct role in the pathogenesis of T2DM. To quantify the interaction between a lack of glucagon suppression with intact, mildly or moderately impaired insulin secretion we studied 45 nondiabetic subjects with and without suppressed glucagon. On both occasions, an intravenous glucose infusion mimicking the systemic appearance of 50g oral glucose was administered in the presence of a pancreatic clamp. Glucagon was infused at a rate of 0.65ng/kg/min, starting at 0 min or 120 min (non-suppressed vs. suppressed respectively). In one group (100%) a nondiabetic insulin profile was infused; another group received 80% of this profile and the third group received 60% of the insulin infused in the first group. We observed that a lack of glucagon suppression increased peak (p &lt; 0.05) and area above basal (AAB) glucose (p &lt; 0.02) in all groups (1.5 ± 0.1 vs. 1.1 ± 0.1; 1.6 ± 0.1 vs. 1.1 ± 0.1; 1.5 ± 0.1 vs.1.3 ± 0.1 Mol per 5hr, 100%, 80%, 60% respectively). These increases were explained by delayed suppression of endogenous glucose production (EGP) so that EGP at 120 minutes was higher (p &lt; 0.05) in the presence of non-suppressed glucagon (6.6 ± 1.0 vs. 4.2 ± 0.6; 7.2 ± 0.8 vs. 5.1 ± 0.5; 7.7 ± 0.8 vs. 5.9 ± 0.6 μmol/kg/min, 100%, 80%, 60% respectively) as was integrated EGP (p &lt; 0.05) over the postprandial period (-1.9 ± 0.4 vs. -2.1 ± 0.1; -1.8 ± 0.1 vs. -1.9 ± 0.2; -1.6 ± 0.3 vs. -1.8 ± 0.1 mmol/kg per 5hr, 100%, 80%, 60% respectively). These data indicate that impaired postprandial glucagon suppression contributes to postprandial hyperglycemia through increased EGP even when insulin secretion is intact as can occur early in prediabetes. These effects are exacerbated by increasing degrees of insulin deficiency.

Disclosure
J. Adams: None. M.C. Laurenti: Employee; Self; GlySens Incorporated. R.A. Rizza: Advisory Panel; Self; Lilly Diabetes, Metavention, Novo Nordisk A/S, vTv Therapeutics. A.M. Egan: None. C. Cobelli: None. C. Dalla Man: None. A. Vella: Advisory Panel; Self; vTv Therapeutics. Research Support; Self; Novo Nordisk Inc.

Funding
National Institutes of Health
1832-P: Impact of Habitual Daily Activity on Glucose Tolerance (GT) and ß-Cell Function in Adults with Impaired GT (IGT) or Type 2 Diabetes (T2D)
Authors: TEMPLE KARLA A. , TJADEN ASHLEY H. , ATKINSON KAREN M. , BARENGOLTS ELENA , HANNON TAMARA S. , MATHER KIEREN J. , UTZSCHNEIDER KRISTINA , EHRMANN DAVID A. , MOKHLESI BABAK ,   RISE CONSORTIUM
Published: June 2019

We examined the relationship between habitual daily activity and measures of GT, insulin sensitivity and β-cell responses in 230 adults (mean age 55 y; BMI 35 kg/m2) with IGT or drug-naïve, recently diagnosed T2D. Participants underwent a 3-h OGTT and hyperglycemic clamp. Wrist accelerometers worn for 7 days measured total activity counts (TAC; daily mean 233,461 {∼ 50th %ile for age}). We evaluated whether TAC predicted fasting plasma glucose (FPG); OGTT 2-h plasma glucose (2-h G) or glucose incremental area under the curve (G-iAUC); hyperglycemic clamp measures of insulin sensitivity (steady-state glucose infusion rate/insulin [M/I]) and β-cell responses (acute C-peptide response to glucose [ACPRg], steady-state C-peptide, maximal β-cell response [ACPRmax]); and OGTT C-peptide index (CPI, [ΔC-Peptide0-30/ΔGlucose0-30]). There was no association of TAC with FPG, 2-h G, or G-iAUC. Higher TAC was associated with higher insulin sensitivity. After adjusting for M/I, higher TAC was associated with lower CPI, but not with clamp-based β-cell responses. Despite similar post-load glucose values, adults with IGT or T2D who were more active demonstrated a greater than expected reduction in C-peptide response given their higher insulin sensitivity. Further studies are needed to understand this dissociation of activity effects on insulin sensitivity and β-cell function.

Disclosure
K.A. Temple: None. A.H. Tjaden: None. K.M. Atkinson: None. E. Barengolts: None. T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. K. Utzschneider: Consultant; Self; Novo Nordisk Inc. D.A. Ehrmann: None. B. Mokhlesi: None. R. Consortium: None.

Funding
National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases
1833-P: PERK Inhibitors Enhanced Glucose-Stimulated Insulin Secretion in a Mouse Model of Type 2 Diabetes
Authors: YANG YE SEUL , KIM MIN JOO , KIM MI NA , KIM JIWON , YOON KUN-HO , PARK KYONG SOO , JUNG HYE SEUNG 
Published: June 2019

Background: PERK (pancreatic endoplasmic reticulum (ER) kinase) has been reported to have important implications in the generation, function, and viability of β cells. We have reported that partial PERK attenuation using PERK inhibitors (PI) enhanced glucose-stimulated insulin secretion (GSIS) from pancreatic islets, through induction of ER chaperone BiP and regulation of ER calcium, but not through the EIF2A-ATF4 pathway. In the current study, we investigated if PI have the same effects under metabolic stress condition.
Methods: GSK2606414, a specific PERK inhibitor, was treated to mouse islets under 20-mM glucose and 0.5-mM palmitate to examine GSIS. Male C57BL/6J mice were fed with high-fat diet combined with streptozotocin injections to mimic type 2 diabetes (DM). Several doses (6 ∼ 16 mg/kg/day) of GSK2656157 and glimepiride were administrated to the mice for 8 weeks, and metabolic phenotypes were evaluated such as body weight, blood glucose levels, insulin secretion and sensitivity, and then changes in the pancreas were measured.
Results: High-glucose and palmitate treatment significantly increased PERK phosphorylation in the isolated islets. Suppression of GSIS and glucose-stimulated Ca2+ transit was also observed. PI at 40 nM which decreased PERK phosphorylation by 40% significantly recovered the GSIS and cytosolic calcium. In the mice where significant weight gain, insulin insufficiency, and prominent hyperglycemia were induced, PI at 10 mg/kg/day significantly enhanced GSIS and reduced blood glucose levels compared to the vehicle. The effects were similar to those by 10 mg/kg/day of glimepiride. Administration of PI did not induce changes in beta cell mass or pancreatic insulin contents, however, high dose PI decreased pancreatic weight.
Conclusion: PI at low dose significantly enhanced GSIS in vitro and in vivo under metabolic stress, and improved hyperglycemia in the mice mimicking type 2 DM, suggesting a potential as a new therapeutic approach for type 2 DM.

Disclosure
Y. Yang: None. M. Kim: None. M. Kim: None. J. Kim: None. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited. K. Park: None. H. Jung: None.

Funding
Korean Ministry of Health and Welfare (A062260)