bluuebunny/crossref_metadata_2025_split huggingface dataset:
1726-P: Male Mice Lacking Estrogen Receptor Beta Develop Obesity but Are Protected from Diet-Induced Insulin Resistance in Skeletal Muscle
Authors: FRIEDLINE RANDALL H. , NOH HYE LIM , SUK SUJIN , GORAL CEREN , DUNPHY KAREN A. , ROBERTS AMY L. , TRAN DUY A. , TAUER LAUREN A. , HU XIAODI , KIM LAUREN H. , KIM ALLISON M. , JERRY D. JOSEPH , KIM JASON K. 
Published: June 2020

Estrogen has an important role in regulating female metabolism. Whereas the role of estrogen receptor (ER) α on female reproductive system is well defined, the role of ERβ (encoded by Esr2) remains unclear. Here we examined the metabolic effects of high-fat diet (HFD) in male Esr2-/- mice on BALB/c background (n=8∼9). After 6 weeks of HFD, Esr2-/- mice became more obese than wild type (WT) mice (Figure 1; *P&lt;0.05). Surprisingly, metabolic cage study showed significantly increased energy expenditure in Esr2-/- mice, likely resulting from skeletal muscle as lean mass tended to be higher in these mice (Figure 2). We performed a hyperinsulinemic-euglycemic clamp to measure insulin sensitivity in awake mice. Despite being more obese, HFD-fed Esr2-/- mice tended to show increased insulin sensitivity with 20% increases in whole body glucose turnover and glycolysis (Figure 3). This was mostly due to a significant increase (52%) in skeletal muscle glucose uptake in HFD-fed Esr2-/- mice (Figure 4). Interestingly, glucose uptake into brown fat tended to be reduced by 50% in HFD-fed Esr2-/- mice.
In conclusion, these results indicate that deletion of Esr2 in male mice increases diet-induced obesity, but selectively prevents muscle insulin resistance. Our findings implicate a potential therapeutic role of estrogen signaling to treat insulin resistance.

Disclosure
R.H. Friedline: None. H. Noh: None. S. Suk: None. C. Goral: None. K.A. Dunphy: None. A.L. Roberts: None. D.A. Tran: None. L.A. Tauer: None. X. Hu: None. L.H. Kim: None. A.M. Kim: None. D. Jerry: None. J.K. Kim: None.

Funding
National Institutes of Health (5U2CDK093000)
1754-P: Prebiotic Early Intervention Improves Blood Glucose in Pup Mice
Authors: ZHANG QIAN , XIAO XINHUA , LI MING 
Published: June 2020

Maternal high fat (HF) during pregnancy is known to have numerous adverse effects on offspring, including increased adiposity and impaired glucose tolerance later in life. The aim of this study was to determine if prebiotic early intervention could mitigate some of the negative effects of maternal HF. C57BL mice were fed a HF diet, normal diet or a HF diet with prebiotic supplementation during pregnancy and lactation. At 3 weeks of age, glucose tolerance were measured in the offspring. And offspring livers were obtained. Hepatic DNA methylation and gene expression was assayed. Maternal HF diet led offspring glucose intolerance and insulin resistance. Prebiotic early intervention moderated glucose metabolism and insulin resistance in male pup mice. Maternal HF diet reduced phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alph (Pik3c2a), phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta (Pik3c2b), and phosphoinositide-3-kinase regulatory subunit 2 (Pik3r2) gene expression in male pup mice (P&lt;0.01). Prebiotic early intervention increased these gene expression in pup livers (P&lt;0.01). Moreover, maternal HF diet led these three gene hypermethylated (P&lt;0.01). These three genes were hypomethylated in prebiotic early intervention group (P&lt;0.01). Prebiotic early intervention improved glucose intolerance by changing DNA methylation and gene expression of Pi3k in mice exposed to a maternal HF diet.

Disclosure
Q. Zhang: None. X. Xiao: None. M. Li: None.

Funding
National Natural Science Foundation of China (81870545, 81870579); Beijing Natural Science Foundation (7202163, 7172169)
1764-P: Specific Viral Targeting of Peripheral Pancreatic Innervation
Authors: GONZALEZ MARIA JIMENEZ , LI ROSEMARY , POMERANZ LISA E. , SCHWARTZ GARY J. , STANLEY SARAH 
Published: June 2020

The brain and peripheral organs communicate through the peripheral nervous system (PNS) comprised of autonomic (sympathetic and parasympathetic) and sensory nerves. Pancreas is densely innervated by the PNS and their cell bodies reside in several ganglia, including nodose (NG), coeliac (CG) dorsal root ganglia (DRG) and intrapancreatic ganglia. Pancreatic innervation is altered in diabetes. Until now, we have lacked the ability to identify and specifically target pancreatic nerves and modulate their function to determine the physiological roles of pancreatic nerves. Here, we delivered retrograde tracers into the pancreas and quantified pancreas-projecting neurons in NG/DRG/CG with 3D visualization and tissue clearing. Next, we assessed the efficiency of different adeno-associated virus (AAV) serotypes, delivery routes and promoters to target construct expression in defined pancreatic nerves. Specific AAV serotypes selectively target pancreas-projecting efferent CG neurons or afferent NG neurons. We utilized Cre-dependent AAV to deliver activating chemogenetic constructs into pancreatic parasympathetic nerves. Targeted activation of the pancreatic parasympathetic neurons improved glucose tolerance and increased insulin secretion. Our studies demonstrate that specific AAV serotypes can target defined pancreatic innervation. Targeted modulation of pancreatic parasympathetic nerves can clarify crucial roles of peripheral nerves in pancreatic function and pathophysiology.

Disclosure
M. Jimenez Gonzalez: None. R. Li: None. L.E. Pomeranz: None. G.J. Schwartz: None. S. Stanley: None.

Funding
American Diabetes Association (1-17-ACE-31 to S.S.); National Institutes of Health (1R01NS097184, OT2OD024912); Alexander and Alexandrine Sinsheimer Scholar Award
1771-P: Hypothalamic Perineuronal Net Assembly Is Required for Sustained Diabetes Remission Induced by FGF1
Authors: ALONGE KIMBERLY M. , MIRZADEH ZAMAN , SCARLETT JARRAD , LOGSDON ARIC , BROWN JENNY M. , CABRALES ELAINE , CHAN CHRISTINA K. , KAIYALA KARL , BENTSEN MARIE A. , BANKS WILLIAM A. , GUTTMAN MIKLOS , WIGHT THOMAS N. , MORTON GREGORY J. , SCHWARTZ MICHAEL W. 
Published: June 2020

Defective glucoregulatory neurocircuit activity within the hypothalamic arcuate nucleus (ARC) is implicated in the pathogenesis of type 2 diabetes (T2D). In the ARC of T2D-Zucker Diabetic Fatty (ZDF) rats, we have identified significant changes in the composition and abundance of extracellular perineuronal nets (PNNs) that enmesh glucoregulatory neurocircuits. Imaging of ARC PNNs, which are comprised of the chondroitin sulfate (CS) proteoglycan aggrecan and attached CS glycosaminoglycans (GAGs), show that T2D-ZDF rats exhibit a 66.4% and 77.3% decrease in aggrecan in the medial and lateral ARC areas, respectively, compared to normoglycemic controls. Distinctive sulfation of the attached CS-GAG isomers (0S-, 4S-, 6S-, 4S6S-, 2S6S-CS) differentially influence the function of PNNs. Using LC-MS/MS, we provide the first description of hypothalamic CS-GAG sulfation patterns and show that in T2D-ZDF rats, levels of the ∆4S- isomer is increased, whereas ∆6S- and ∆2S6S-CS isomers are decreased, differences predicted to disrupt protein-GAG interactions involved in neurite outgrowth and favor tissue stiffening. To determine if ARC PNNs are targets for the antidiabetic effect of fibroblast growth factor 1 (FGF1), we performed intracerebroventricular (icv) injection of FGF1 in ZDF rats and report that both the hypothalamic CS-GAG sulfation patterns and content of ARC PNNs are normalized 24 d after treatment. Western blot analysis shows that the latter effect entails a 1.7-fold increase in aggrecan protein abundance. To assess the functional significance of ARC PNN restoration by FGF1, ZDF rats received an icv FGF1 injection followed by bilateral microinjection of either ChABC, a PNN digesting enzyme, or its vehicle control into the ARC. Our finding that the duration of sustained FGF1-induced blood glucose lowering was shortened following ARC PNN digestion (p&lt;0.05) identifies PNNs as novel participants in the central control of glucose homeostasis and diabetes remission by FGF1.

Disclosure
K.M. Alonge: Research Support; Self; Novo Nordisk Inc. Z. Mirzadeh: None. J. Scarlett: None. A. Logsdon: None. J.M. Brown: None. E. Cabrales: None. C.K. Chan: None. K. Kaiyala: None. M.A. Bentsen: None. W.A. Banks: None. M. Guttman: None. T.N. Wight: None. G.J. Morton: Research Support; Self; Novo Nordisk A/S. M.W. Schwartz: Research Support; Self; Novo Nordisk A/S.

Funding
National Institutes of Health (P30DK017047, F32DK122662, R01DK101997, R01DK089056, R01DK083042, K08DK114474, R01GM127579, K12NS080223, P30DK035816); Barrow Neurological Foundation (1800253005); University of Washington; Novo Nordisk (CMS431104); Novo Nordisk Foundation (NNF170C0024328, NNF10CC1016515)
1779-P: Liraglutide + Metformin Delays Worsening of Glycemia in Adults with Impaired Glucose Tolerance (IGT) or Type 2 Diabetes (T2D)
Authors: SAM SUSAN , EDELSTEIN SHARON , UTZSCHNEIDER KRISTINA , HANNON TAMARA S. , BARENGOLTS ELENA , XIANG ANNY , EHRMANN DAVID A. , MATHER KIEREN J. , KAHN STEVEN E. ,   THE RISE CONSORTIUM
Published: June 2020

The Restoring Insulin Secretion (RISE) Study examined the effect of medications to preserve β-cell function in 267 adults with IGT or drug-naïve, recently diagnosed T2D. Participants were randomized to receive 12 months of blinded metformin (MET) or placebo, 12 months of liraglutide (LIRA)+MET, or 3 months of glargine followed by 9 months of MET, all followed by 9 months off treatment. We examined glycemic worsening, defined as progression from IGT to diabetes by fasting or 2-h glucose on an OGTT at baseline, 6, 12, 15 and 21 months or a rise in quarterly HbA1c to ≥7%s. Time-to-worsening was evaluated across treatment groups using a modified product-limit life-table distribution with a log-rank test. Compared to the other treatments, LIRA+MET had less glycemic worsening at 12 months (on treatment) and 21 months (9 months off treatment); each p&lt;0.01. After stopping treatment, group differences persisted but all groups showed similar rates of glycemic progression (Figure). Using logistic regression, independent predictors of worsening glycemia by months 12 and 21 were treatment with LIRA+MET (p=0.01; p=0.03) and baseline 2-h glucose (p=0.02; p=0.03). Overall, despite similar rates of glycemic worsening after discontinuation of therapy, the sustained on-treatment interval of normoglycemia resulted in less glycemic worsening in LIRA+MET compared with the other RISE interventions.

Disclosure
S. Sam: None. S. Edelstein: None. K. Utzschneider: Other Relationship; Self; Medtronic. T.S. Hannon: None. E. Barengolts: None. A. Xiang: None. D.A. Ehrmann: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None.

Funding
American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases
1780-P: Differential Effects of Medications and Gastric Banding on OGTT-Modeled Measures of ß-Cell Function in Adults with IGT or Recent-Onset Type 2 Diabetes (T2D)
Authors: UTZSCHNEIDER KRISTINA , GHORMLI LAURE EL , SAM SUSAN , EHRMANN DAVID A. , MATHER KIEREN J. , BARENGOLTS ELENA , HANNON TAMARA S. , TRIPPUTI MARK , EDELSTEIN SHARON , MARI ANDREA ,   THE RISE CONSORTIUM
Published: June 2020

We compared 3-hr OGTT model-derived measures of insulin sensitivity and β-cell function after 12 mo treatment with placebo (PLAC), metformin (MET), liraglutide plus MET (L+M), 3 mo glargine followed by 9 mo MET (G/M) and gastric banding (GB) in adults with IGT or T2D in the Restoring Insulin Secretion (RISE) Study. Modeling parameters included insulin sensitivity (OGIS), insulin secretion rate (ISR) at reference glucose 6.5 mM (ISR@6.5), total integrated ISR (tISR), glucose sensitivity (GS: slope ISR vs. glucose concentration) and rate sensitivity (RS: ISR relative to glucose rate of change). Adjusted linear mixed models compared model parameters over time within and between each study arm.
Results: Baseline model parameters did not differ by treatment arm. OGIS increased in all groups except PLAC. ISRs and GS increased in L+M but decreased or were unchanged in the other treatment arms. RS only increased in the G/M and GB arms. Treatment effects differed by arm. For L+M, GS and ISRs were increased vs. all other arms. For GB, RS was increased and tISR decreased vs. PLAC and GS was increased vs. MET.
In summary, L+M augments insulin secretion and increases GS, while GB increases RS. Clinically, both L+M and GB appear to improve β-cell function at 12 mo and may benefit adults with IGT or recent-onset T2D while on treatment.

Disclosure
K. Utzschneider: Other Relationship; Self; Medtronic. L. El Ghormli: None. S. Sam: None. D.A. Ehrmann: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. E. Barengolts: None. T.S. Hannon: None. M. Tripputi: None. S. Edelstein: None. A. Mari: Consultant; Self; Lilly Diabetes. Research Support; Self; Boehringer Ingelheim International GmbH. T. Consortium: None.

Funding
American Diabetes Association (1-14-RISE-01); National Institute of Diabetes and Digestive and Kidney Diseases
1787-P: Insulin Pulse Characteristics Do Not Alter Hepatic Glucose Metabolism and Insulin Action
Authors: LAURENTI MARCELLO C. , MAN CHIARA DALLA , VARGHESE RON T. , JONES JOHN , BAROSA CRISTINA , RIZZA ROBERT A. , MATVEYENKO ALEKSEY , NICOLAO GIUSEPPE DE , COBELLI CLAUDIO , VELLA ADRIAN 
Published: June 2020

Insulin is secreted into the portal vein in a pulsatile manner. Portal vein insulin concentrations directly and rapidly alter endogenous glucose production (EGP). Pulse frequency has been inversely correlated with hepatic insulin action in some, but not all, human studies. Indeed, increased pulse disorderliness, decreased secretory burst mass and decreased pulse frequency have been observed in type 2 diabetes, in aging and in obesity. In dogs, disruption of pulsatile insulin secretion is associated with defects in hepatic insulin action. As part of a series of experiments examining the mechanisms underlying prediabetes, we studied 29 nondiabetic subjects (BMI 28 ± 1 Kg/m2) on 2 occasions. On one occasion, EGP was measured using [3-3H]glucose after an overnight fast (14.2 ± 0.5μmol/kg/min) and during a euglycemic clamp (6.8 ± 1.1μmol/kg/min). The deuterated water method was used to estimate the contribution of gluconeogenesis to EGP. On a separate study day we utilized nonparametric stochastic deconvolution of frequently sampled peripheral C-peptide concentrations during fasting to reconstruct portal insulin secretion. In addition to measuring basal and pulsatile insulin secretion, we used Approximate Entropy (ApEn) to measure orderliness and a Fourier transform to measure the average and the dispersion of insulin pulse frequency. The gradient of Loge EGP vs. Loge insulin in each individual (-1.2 ± 0.5) was used as a measure of hepatic insulin action. Basal secretion (126 ± 8 pmol/min, R2=0.04), pulse amplitude (41 ± 38 pmol/min, R2=0.02), ApEn (1.14 ± 0.03, R2=0.01), pulse interval (5.7 ± 0.4 min, R2&lt;0.01) and frequency dispersion (0.47 ± 0.01, R2&lt;0.01) did not correlate (all p &gt; 0.10) with hepatic insulin action. Suppression of gluconeogenesis by insulin also did not correlate with fasting insulin pulse characteristics. Overall, our data demonstrate that insulin pulse characteristics do not directly alter the sensitivity of EGP and gluconeogenesis to insulin in humans.

Disclosure
M.C. Laurenti: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. R.T. Varghese: None. J. Jones: None. C. Barosa: None. R.A. Rizza: None. A. Matveyenko: None. G. De Nicolao: None. C. Cobelli: None. A. Vella: Advisory Panel; Self; vTv Therapeutics, Zealand Pharma A/S. Research Support; Self; Novo Nordisk A/S, Xeris Pharmaceuticals, Inc.

Funding
National Institutes of Health (DK78646, DK116231)
179-LB: Characteristics of Children with Medication-Induced Diabetes (MID): A Canadian Pediatric Surveillance Program (CPSP) Study
Authors: PATEL TRISHA J. , AYUB AYSHA , IRVINE MICHAEL A. , HADJIYANNAKIS STASIA , HENDERSON MÉLANIE , NOUR MUNIER A. , PINTO TERESA , WICKLOW BRANDY , HAMILTON JILL , SELLERS ELIZABETH , AMED SHAZHAN 
Published: June 2020

Objectives: There is limited data on MID in children. This study aimed to compare the demographic and clinical characteristics of 1) a historical MID cohort to a new cohort and 2) children with MID based on overweight/obese BMI (O-BMI) and normal weight BMI (N-BMI).
Methods: National surveillance was conducted via the CPSP. Pediatric clinicians reported new cases (children &lt;18 years old) of non-type 1 diabetes for 24-months (cohort 1: 2006-08, cohort 2: 2017-19). MID cases were classified by the presence of diabetes as defined by Diabetes Canada and exposure to a diabetogenic medication. Comparisons were made between the two cohorts and between MID patients with O-BMI (BMI ≥85th percentile for age and sex) and N-BMI (BMI &lt;85th percentile for age and sex). Descriptive statistics and Fisher exact, chi-squared and t-tests were used where applicable.
Results: There were 55 cases of MID in cohort 1 and 51 cases in cohort 2, with no significant differences between cohorts. Mean age (+/- SD) at presentation was 13.1 +/- 3.6 years and 13.3 +/- 3.5 years in cohort 1 and 2, respectively. Glucocorticoid therapy was documented in &gt;95% of cases in both cohorts. In the combined cohorts there were 50 cases with N-BMI and 43 cases with O-BMI. There were no statistically significant differences in age, sex or ethnicity across BMI groups. Mean hemoglobin A1c (+/- SD) (n = 40) was 6.45% +/- 1.11% in the N-BMI group and 7.26% +/- 2.51% in the O-BMI group (p = 0.184). The O-BMI group were more likely to have a parent with type 2 diabetes (T2D) (p = 0.042) and acanthosis nigricans (p = 0.007) compared to the N-BMI group.
Conclusions: The demographic and clinical features of children with MID have not changed over a 10-year period. The presence of acanthosis nigricans and/or a parent with T2D may be used to identify children who require more intensive glycemic monitoring when on a diabetogenic medication. Further studies are needed to better understand the evolution of MID and the risk it confers to developing T2D.

Disclosure
T.J. Patel: None. A. Ayub: None. M.A. Irvine: None. S. Hadjiyannakis: None. M. Henderson: None. M.A. Nour: None. T. Pinto: None. B. Wicklow: None. J. Hamilton: None. E. Sellers: None. S. Amed: None.

Funding
Diabetes Canada; Manitoba Institute for Child Health and Sick Kids Hospital; Public Health Agency of Canada (F18-02353)
1796-P: A-ß+ Ketosis-Prone Diabetes (KPD) Patients Augment Insulin Response to Arginine but Not to Glucose after Sustained Hyperglycemia
Authors: HSU JEAN W. , CARDENAS ADRIANA J. , GABA RUCHI , TOSUR MUSTAFA , RAM NALINI , GUTIERREZ ABSALON D. , BOHREN KURT M. , CADUCOY EUNICE I. , JAHOOR FAROOK , BALASUBRAMANYAM ASHOK 
Published: June 2020

We previously showed that patients with A-β+ KPD (“obese ketosis-prone type 2 diabetes”) have diminished intracellular arginine availability that may impair their ability to generate an adequate beta cell response in the face of hyperglycemia, and thus make them vulnerable to develop ketoacidosis (Mulukutla et al, J Nutr 2018). To investigate further their β cell responsiveness to exogenous arginine, we studied 9 recently diagnosed, stable, near-normoglycemic A-β+ KPD patients and 10 age-, sex- and BMI-matched nondiabetic controls with dynamic measures of insulin and C-peptide responses to glucose or arginine bolus under two conditions: in the euglycemic, fasting (basal) state and after a 5h hyperglycemic clamp. In the basal state, total and first phase insulin areas under the curve (AUC) in response to glucose were significantly greater in controls than KPD (total AUC 1756 ± 298 vs. 857 ± 126 min·µU/mL; P = 0.05); after hyperglycemia, AUC insulin response to glucose remained significantly greater in controls (total AUC 2470 ± 296 vs. 1512 ± 316 min·µU/mL; P = 0.04), and KPD patients mounted only a non-significant increase in total AUC insulin compared to the basal state (P = 0.12). In contrast, total and first phase AUC insulin in response to arginine in the basal state was similar in controls and KPD (total AUC 544 ± 85 vs. 337 ± 50 min·µU/mL; P = 0.75). After hyperglycemia, although AUC insulin response to arginine was greater in controls (total AUC 1854 ± 2227 vs. 1149 ± 207 min·µU/mL; P = 0.002), the KPD patients mounted a significant 70% increase in total AUC insulin compared to the basal state (P = 0.002). C-peptide responses mirrored those of insulin under all conditions. Thus, KPD patients exhibit a robust β cell response to arginine but not to glucose, both during fasting euglycemia and after sustained hyperglycemia. Exogenous arginine could augment insulin secretion during hyperglycemia and prevent the episodes of ketoacidosis that characterize A-β+ KPD.

Disclosure
J.W. Hsu: None. A.J. Cardenas: None. R. Gaba: None. M. Tosur: None. N. Ram: None. A.D. Gutierrez: Speaker’s Bureau; Self; AstraZeneca. K.M. Bohren: None. E.I. Caducoy: None. F. Jahoor: None. A. Balasubramanyam: None.

Funding
National Institutes of Health (R01DK101411)
1799-P: Insulin Secretion during a Graded Glucose Infusion Correlates with GPS2 mRNA Expression in Adipocytes
Authors: VELHO GILBERTO , DRARENI KARIMA , NGUEWA JEAN-LOUIS , ROUSSEL RONAN , RIVELINE JEAN-PIERRE , VENTECLEF NICOLAS , GAUTIER JEAN-FRANÇOIS 
Published: June 2020

The transcriptional corepressor GPS2 plays a key role in human adipose tissue homeostasis. Decreased expression of GPS2 in adipocytes was associated with increased expression of inflammatory genes and with a pro-diabetic status. Here we assessed associations of GPS2 expression in adipocytes with insulin secretion in human volunteers. Dose response relationships between glucose and insulin secretion rates (ISR) were studied in 22 people (7 with normal glucose tolerance and 15 with type 2 diabetes; aged 48±12 years; men 68%) following a stepped intravenous glucose infusion at 2, 4, 6, 8 and 10 mg/kg/min. ISR was derived by deconvolution of plasma C-peptide level. GPS2 mRNA was quantified in adipose tissue biopsies by RT-qPCR. Participants were stratified by GPS2 mRNA expression into low (Lexp) or high expression (Hexp), defined by values below or above the median. Basal glucose level and ISR were higher in Lexp than in Hexp participants: 8.0±0.5 vs. 5.6±0.3 mmol/l, mean±SEM, p=0.0008, and 3.04±0.19 vs. 2.12±0.17 pmol/kg/min, p=0.002, respectively. Following glucose infusion, glucose level increased by 178±17% and 174±23% (p=0.88) in Lexp and Hexp participants, with average values of 14.9±0.6 and 11.4±0.78 mmol/l (p=0.002), respectively. Concomitant ISR increased by 236±40% and 487±75% (p=0.006) in Lexp and Hexp participants. Average ISR following glucose infusion (10-200 min) was 5.40±0.67 vs. 8.49±0.75 pmol/kg/min, p=0.01, respectively. Average ISR correlated positively with GPS2 expression: r2=0.34, p=0.004. Analysis of the glucose/ISR response curve demonstrated significantly higher ISR in Hexp than in Lexp participants at all glucose levels (p=0.005, adjusted for sex, age, BMI, and glycemic status). It was ∼52%, ∼60% and ∼45% higher at 7, 10 and 15 mmol/l glucose, respectively. Our results suggest a potential role for GPS2 in adipocyte-pancreatic beta cells cross-talk regulation of insulin secretion response to glucose, in line with previous experimental findings.

Disclosure
G. Velho: None. K. Drareni: None. J. Nguewa: None. R. Roussel: Advisory Panel; Self; Abbott, AstraZeneca, Diabnext, Eli Lilly and Company, Merck & Co., Inc., Mundipharma International, Novo Nordisk A/S, Sanofi-Aventis. J. Riveline: None. N. Venteclef: None. J. Gautier: None.