bluuebunny/crossref_metadata_2025_split huggingface dataset:
1939-P: Intermuscular Adipose Tissue Has a Metabolically Adverse Secretome Compared with Visceral and Subcutaneous Depots
Authors: KAHN DARCY E. , MACIAS EMILY , ZARINI SIMONA , HARRISON KATHLEEN A. , CREE-GREEN MELANIE , BERGMAN BRYAN C. 
Published: June 2019

Adipose tissue is a dynamic secretory organ that has differing effects on metabolic disease depending upon location and composition. Resting beneath the fascia, and bordering muscle fibers, intermuscular adipose tissue (IMAT) secretes proteins and lipid signaling molecules that are uniquely positioned to directly impact insulin sensitivity and inflammation in skeletal muscle. Individuals with Obesity and type 2 diabetes have increased IMAT volume, and while IMAT is inversely correlated with muscle strength, function, and insulin sensitivity, the mechanisms by which it exerts these effects are unknown. We quantified the secretome of IMAT, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) to determine if there are differences between depots in the secretion of cytokines, eicosanoids, FFAs and proteins that influence metabolic function. SAT and VAT biopsies from bariatric surgery patients and IMAT from the vastus lateralis biopsies of individuals with Obesity were cultured for 48 hours in DMEM, and the conditioned media was analyzed using nanoflow HPLC-MS, multiplex ELISAs and LC/MS/MS for proteins, cytokines and eicosanoids/FFA, respectively. IMAT secretion of various extracellular matrix proteins was significantly different than VAT and SAT. Pro-inflammatory cytokine secretion of IFNγ, TNFα, IL-8 and IL-13 from IMAT was higher than VAT and significantly higher than SAT (p &lt; 0.05). IMAT secretes significantly more pro-inflammatory eicosanoids TXB2 and PGE2 than VAT (p = 0.02, 0.05) and SAT (p = 0.01, 0.04). IMAT and VAT have significantly greater basal lipolysis assessed by FFA release rates compared to SAT (p = 0.01, 0.04). These data begin to characterize the disparate secretory properties of SAT, VAT and IMAT that may impact tissue function, and suggest that the metabolically adverse secretome of IMAT, with such proximity to skeletal muscle may play an important functional role in the pathogenesis of insulin resistance and type 2 diabetes.

Disclosure
D.E. Kahn: None. E. Macias: None. S. Zarini: None. K.A. Harrison: None. M. Cree-Green: None. B.C. Bergman: Advisory Panel; Spouse/Partner; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc.

Funding
National Institutes of Health (R01DK118149, RR-00036); Colorado Nutrition Obesity Research Center (P30DK048520)
194-LB: Effectiveness of Following Mediterranean Diet (MedDiet) Recommendations in the Real World in the Incidence of Gestational Diabetes Mellitus (GDM) and Adverse Maternal-Fetal Outcomes: A Prospective, Universal Interventional Study
Authors: DURAN ALEJANDRA , DE LA TORRE NURIA GARCIA , ASSAF-BALUT CARLA , DEL VALLE LAURA , INES JIMENEZ , VALERIO DEOGRACIA JOHANNA , BORDIU ELENA , FUENTES MANUEL , BARABASH ANA , CUESTA MARTIN , RUBIO MIGUEL A. , CALLE ALFONSO L. 
Published: June 2019

Background: We previously reported that a MedDiet, supplemented with extra-virgin olive oil (EVOO) and pistachios, reduces GDM incidence (WHO criteria) and several adverse outcomes. To assess effects in the in the real world we evaluated the adoption of a MedDiet starting at the 1st gestational visit on the rate of GDM (compared with the control group/CG and intervention group/IG from the previous trial). We also compared the rate of adverse perinatal outcomes between women with and without GDM.
Research Design and Methods: This is a prospective, clinic-based, interventional study with a single group. All normoglycemic women attending their 1st gestational visit &lt;12 gestational weeks (GW) between November 2016-2017 were invited to participate; 1066 signed an informed consent. Women received lifestyle guidance with emphasis on consuming EVOO and nuts daily. 932 women were analyzed. Binary regression analyses were performed to assess the risk of pregnancy-induced hypertension, preeclampsia, gestational weight gain (GWG), C-section, perineal trauma, preterm delivery, small/large-gestational-age new-borns and admissions in neonatal ICU and observation.
Results: GDM rate was of 13.9%; this was significantly lower than the CG: RR 0.81 (0.73-9.28),p&lt;0.001 and no different to the IG:RR 0.96 (0.85-1.07),p=0.468. GWG (kg) was lower in GDM women (10.88±6.46 vs. 12.30±5.42; p=0.013). Excessive weight gain was also lower (RR 0.91 (0.86-0.96)) without a significant increase of insufficient weight gain. We found no differences in any perinatal adverse outcomes.
Conclusion: This study translates evidence to clinical practice, providing a universal and easy-to-apply approach to reduce GDM. An early nutritional intervention before GDM diagnosis ameliorates differences in maternofoetal adverse outcomes between GDM and no-GDM women.

Disclosure
A. Duran: None. N. Garcia de la Torre: None. C. Assaf-Balut: None. L. Del Valle: None. J. Ines: None. J. Valerio Deogracia: None. E. Bordiu: None. M. Fuentes: None. A. Barabash: None. M. Cuesta: None. M.A. Rubio: None. A.L. Calle: None.

Funding
Instituto de Salud Carlos III of Spain; Fondo Europeo de Desarrollo Regional; Sociedad de Endocrinolog?a Nutrici?n y Diabetes de la Comunidad de Madrid (IPI/2017/NR2)
1958-P: Role of Leptin in Blood-Brain Barrier Dysfunction
Authors: SALAMEH THERESE S. , MORTELL WILLIAM , BANKS WILLIAM A. 
Published: June 2019

All forms of diabetes mellitus are characterized by chronic hyperglycemia resulting in the development of a number of microvascular and macrovascular pathologies. Diabetes is also associated with changes in brain microvasculature leading to dysfunction and disruption of the blood-brain barrier (BBB). These changes are correlated with a decline in cognitive function. The BBB is a regulatory interface between brain and blood, preventing the unrestricted leakage of plasma proteins into the central nervous system (CNS) and performing nutritive, homeostatic, and communication roles. Studies have shown that in a streptozotocin-induced mouse model of type 1 diabetes, where insulin and leptin levels are low, BBB dysfunction occurs in five brain regions: frontal cortex, occipital cortex, parietal cortex, midbrain, and thalamus. In contrast, in a diet induced obese (DIO) model of type 2 diabetes, where insulin and leptin levels are high, BBB dysfunction did not occur in those five regions but did occur in the hippocampus and hypothalamus. In both models, all mice were hyperglycemic, indicating that this is not the only mechanism by which BBB dysfunction occurs. To further investigate the role of the hormones leptin and insulin in BBB dysfunction, we utilized the BTBR.Cg-Lepob/WiscJ ob/ob mice, a transgenic model of type 2 diabetes where insulin is high and no leptin is present. Using radioactively labeled ligands, we have demonstrated that loss of leptin leads to BBB dysfunction in all brain regions as early as four weeks of age. Importantly, these mice are not born with this dysfunction as studies in two-day old pups demonstrate an intact BBB. Replenishment of leptin to these BTBR.Cg-Lepob/WiscJ ob/ob mice from birth was able to attenuate BBB dysfunction observed at four-weeks of age. These studies indicate that leptin is a key component in maintaining BBB integrity in diabetes.

Disclosure
T.S. Salameh: None. W. Mortell: None. W.A. Banks: None.

Funding
National Institute of Neurological Disorders and Stroke (1R21NS093368-01A1)
1959-P: Upregulation of PYY, GLP-1, and NTS by Intermittent Hypoxia in Enteroendocrine Cells
Authors: SHOBATAKE RYOGO , OTA HIROYO , ITAYA-HIRONAKA ASAKO , YAMAUCHI AKIYO , MAKINO MAI , SAKURAMOTO-TSUCHIDA SUMIYO , UCHIYAMA TOMOKO , TAKAHASHI NOBUYUKI , UENO SATOSHI , SUGIE KAZUMA , TAKASAWA SHIN 
Published: June 2019

The patients with sleep apnea syndrome (SAS) are exposed to intermittent hypoxia (IH) during sleep. Although accumulating evidence indicates a strong relationship between SAS and obesity, we previously demonstrated that IH up-regulates the mRNA levels of anorexigenic peptides POMC and CART via GATA transcription factors in human neuronal cells (Int. J. Biochem. Cell Biol. 95, 100, 2018). Appetite is regulated not only by the central nervous system but also by gastrointestinal peptides. Here, we investigated the effect of IH on the appetite-inhibiting gut hormone expression using in vitro IH system. Human and mouse enteroendocrine cells, Caco-2 and STC-1, were exposed to IH [64 cycles of 5 min hypoxia (1% O2) and 10 min normoxia (21% O2)] or normoxia for 24 hours. Real-time RT-PCR revealed that IH significantly increased the mRNA levels of PYY, GLP-1, and neurotensin (NTS) in both Caco-2 and STC-1. ELISA showed that the concentrations of PYY, GLP-1, and NTS in the culture medium were significantly increased by IH. To determine whether the IH-induced increases in PYY, GLP-1, and NTS in enteroendocrine cells were caused by transcriptional activation, reporter plasmids for PYY, GCG, which encodes a preprotein, part of which is cleaved into GLP-1, and NTS were transfected into Caco-2, and the luciferase activity was measured after the IH treatment. The promoter activities of PYY, GCG and NTS were not increased by IH. We then searched targeted miRNA and found that PYY, GLP-1 and NTS mRNAs have potential target sequences for miR-96, -527, and -2116. We measured the levels of the miRNAs and found that the levels of the miRNAs were not decreased by IH. Furthermore, the mRNA levels of PYY, GLP-1, and NTS were significantly up-regulated even in normoxia by trichostatin A and were significantly decreased even in IH by 5-azacytidine, suggesting that IH increases PYY, GLP-1, and NTS mRNAs via alterations in the chromatin structure in enteroendocrine cells. IH might have an anorexigenic influence on the enteric nervous system.

Disclosure
R. Shobatake: None. H. Ota: None. A. Itaya-Hironaka: None. A. Yamauchi: None. M. Makino: None. S. Sakuramoto-Tsuchida: None. T. Uchiyama: None. N. Takahashi: None. S. Ueno: None. K. Sugie: None. S. Takasawa: None.
196-OR: Pharmacological Modulation of Prostaglandin E2 Receptor Activity Enhances ß-Cell Mass in a Mouse Model of Type 2 Diabetes and Human Islets
Authors: ANDREI SPENCER R. , DUNN JENNIFER C. , CHRISTENSEN ASHLEY A. , RICCIARDI VALERIE F. , PACE WILLIAM A. , BREYER RICHARD M. , GANNON MAUREEN 
Published: June 2019

Type 2 diabetes (T2D) is characterized by chronic hyperglycemia and low-grade inflammation. Failure to expand β-cell mass in response to insulin resistance can lead to T2D. The hyperglycemia and chronic inflammation observed in T2D is associated with enhanced levels of prostaglandin E2 (PGE2) synthesis in pancreatic islets. Downstream effects of PGE2 signaling are carried out by four E-Prostanoid (EP) G-protein coupled receptors, EP1-4. Recent investigations by our lab demonstrated that EP3 and EP4 play opposing roles in pancreatic islets whereby EP3 activation inhibits β-cell proliferation and survival while EP4 activation stimulates β-cell mass expansion and reduces cytokine-induced cell death ex vivo. Preliminary data suggests that db/db mice (a model of T2D) treated with the EP3 antagonist, DG-041, exhibit enhanced levels of β-cell proliferation when compared to their vehicle-treated counterparts (3.04 ± 0.6% Ki67+/Ins+ β-cells and 1.67 ± 0.2%, respectively). Although differences in β-cell death between the vehicle- (0.09 ± 0.1% TUNEL+ β-cells) and DG-041-treated cohorts (0.23 ± 0.1%) did not reach statistical significance, treatment with the EP3 antagonist ultimately culminated in improved β-cell mass in db/db mice (1.57 ± 0.2 mg) compared to vehicle-treated controls (0.94 ± 0.2 mg). Additionally, preliminary results suggest that the EP3 antagonist-induced increase in β-cell proliferation in nondiabetic human cadaver donors occurs, in part, through PLCγ-1 whereby pretreatment of human islets with U-73122 (PLCγ-1 inhibitor) prior to DG-041 addition resulted in decreased β-cell proliferation (1.67 ± 0.2 fold of vehicle-treated control) when compared to the EP3 antagonist alone (2.30 ± 0.3 fold). Taken together, these results provide valuable foundational insight into the potential role of EP3 in the modulation of β-cell mass expansion.

Disclosure
S.R. Andrei: None. J.C. Dunn: None. A.A. Christensen: None. V.F. Ricciardi: None. W.A. Pace: None. R.M. Breyer: None. M. Gannon: None.
1963-P: Undercarboxylated Osteocalcin Is Correlated with Insulin Secretion in Japanese Individuals with Diabetes
Authors: FUNAKOSHI SHOGO , OHMI SATOKO , AMANO ERI , TERADA YOSHIO , FUJIMOTO SHIMPEI 
Published: June 2019

Background and Aims: Undercarboxylated osteocalcin (ucOC) is a secreted protein produced by osteoblasts. UcOC can regulate insulin secretion and insulin sensitivity in rodents. Pharmacological administration of ucOC enhances insulin secretion which could be mediated by GLP-1 in mice. However, pathophysiological roles of ucOC in glucose intolerance in human remain unknown. In this study, we aimed to investigate the association between ucOC and glucose metabolism in individuals with varying degrees of glucose tolerance.
Materials and Methods: The 75-g oral glucose tolerance test was carried out in 75 Japanese individuals not taking diabetes medications [age: 65±11 (mean±SD); male/female: 34/41; BMI: 24.9±3.8]. Individuals were classified as normal (NGT), impaired glucose tolerance (IGT), and diabetes (DM) groups (each group: n=25). The insulinogenic index (IGI) as an index of insulin secretion, and QUICKI and the Matsuda Index (MI) as indices of insulin sensitivity were calculated. Fasting serum levels of ucOC and leptin were assayed by ECLIA and by ELISA, respectively. Normally-distributed loge-transformed (ln-)values were used for regression analysis in some cases.
Results: Although fasting and 2h after glucose loading plasma glucose, HbA1c, IGI, QUICKI and MI were significantly different among the 3 groups, age, sex, BMI, and ucOC were not different. In simple regression analysis in each group, ln-ucOC was not correlated with QUICKI and ln-MI in all 3 groups. Interestingly, ln-ucOC was correlated with ln-IGI (r=0.422, P=0.0345) and HbA1c (r=-0.574, P=0.0022) only in DM. In multiple regression analysis in DM, ln-IGI was independently predicted by BMI (β=0.598) and ln-ucOC (β=0.641) (R2=0.488, P=0.0006) and by ln-leptin (β=0.624) and ln-ucOC (β=0.448) (R2=0.568, P&lt;0.0001).
Conclusion: UcOC was correlated with insulin secretion independently of adiposity in Japanese individuals with diabetes.

Disclosure
S. Funakoshi: None. S. Ohmi: None. E. Amano: None. Y. Terada: None. S. Fujimoto: None.
1968-P: Improved Glucose Tolerance via Somatostatin Receptor Antagonism Is an Effect Mediated by the Intestine
Authors: JEPSEN SARA L. , HOLST JENS J. 
Published: June 2019

Antagonising the peptide hormone somatostatin (SS) is a novel promising approach to improve glycaemic control. SS inhibits secretion of glucagon-like peptide-1 (GLP-1), via binding to five SS receptors (SSTr1-5). Subtype specific SSTr antagonists can improve glycaemic control after an oral glucose tolerance test (OGTT) in mice, but the mechanism is still unclear. We hypothesized that the effect on glucose tolerance by antagonising SS may be intestinally derived involving GLP-1 rather than a direct effect on the pancreas. We investigated whether addition of a DPP-4 inhibitor would enhance the effect on glucose tolerance by subcutaneous (s.c.) injection of two SSTr antagonists specific for SSTr2 (SSTr2a) and SSTr5 (SSTr5a) in vivo in mice. Next, we used the same antagonists together with s.c. glucose to avoid release of endogenous incretins to estimate the intestinal contribution. Using SSTr5 knockout (KO) mice, which already have improved glycaemic control, we did an OGTT in combination with a GLP-1 receptor antagonist (exendin9-39) to see if the effect is mediated by the GLP-1 receptor. Both SSTr2a and SSTr5a lowered blood glucose levels (AUC) compared to the control group (PBS 34.06 (mmol/l)×min, SSTr2a 23,35 (mmol/l)×min, SSTr5a 26.59 (mmol/l)×min). The DPP-4 inhibitor in combination with SSTr2a markedly lowered glucose levels (AUC after SSTr2a+DPP-4 inhib: 9.8 (mmol/l)×min) whereas the combination with SSTr5a resulted in a minor additive effect (SSTr5a+DPP-4 inhib: 19.7 (mmol/l)×min). Interestingly the effect of the SSTr antagonists was completely lost when glucose was given s.c. and no lowering effect on glucose was observed. In SSTr5 KO mice, glucose tolerance was improved compared to wild type (WT) littermates (WT 30.6 (mmol/l)×min), SSTr5 KO 17.9 (mmol/l)×min), which was markedly impaired when given Exendin9-39. These studies strongly suggest that the effects of antagonising SS are mediated by a GLP-1 based mechanism derived from the intestine.

Disclosure
S.L. Jepsen: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S.
197-LB: Factors Associated with Screening for Diabetes in Low-Income Women after a Pregnancy with Gestational Diabetes
Authors: HERRICK CYNTHIA J. , YAN YAN , TROLARD ANNE , COOPER BENJAMIN P. , KELLER MATTHEW , OLSEN MARGARET A. 
Published: June 2019

Background: Gestational diabetes (GDM) increases risk for type 2 diabetes seven fold. Women with a history of GDM should be screened for diabetes at 4-12 weeks postpartum and every 1-3 years thereafter. We aimed to characterize factors associated with diabetes screening by 12 weeks and 1 year postpartum in a cohort of low-income women with GDM.
Methods: A retrospective cohort of 1078 women with GDM who delivered from 2010-2015 was generated by linking electronic health record data from 21 Missouri Federally Qualified Health Centers (FQHCs) with Medicaid administrative claims. Screening rates for diabetes were calculated within 12 weeks and one year of delivery. Two multivariable logistic regression models were constructed to determine associations with recommended screening at these time points. Models were adjusted for age, race/ethnicity, comorbidities, prenatal care, previous birth, and distance from home to health center.
Results: Median age was 28 years and 64% of women were racial and ethnic minorities (41% black non-Hispanic). Recommended postpartum screening occurred in 9.7% of women by 12 weeks and 18.9% by 1 year. At 12 weeks and 1 year postpartum, having a prenatal certified diabetes educator visit (12 weeks: aOR 1.9 95% CI 1.1-3.5; 1 year aOR 2.2 95% CI 1.3-3.5) and prior medication for GDM (12 weeks: aOR 2.5 95% CI 1.4-4.3; 1 year aOR 2.7 95% CI 1.7-4.2) were strongly associated with diabetes screening. At 1 year, living in an area with public transportation increased odds of screening two-fold (aOR 2.0 95% CI 1.1-3.8) and each additional encounter with the health system after delivery increased odds of screening by 16% (95% aOR 11-21%).
Discussion: Multiple factors are associated with postpartum screening for diabetes in populations with limited resources. Future interventions to increase screening should focus on enhancing access to prenatal certified diabetes education and addressing barriers related to transportation and health system access.

Disclosure
C.J. Herrick: Stock/Shareholder; Spouse/Partner; Cardinal Health. Y. Yan: None. A. Trolard: None. B.P. Cooper: None. M. Keller: None. M.A. Olsen: Consultant; Self; Pfizer Inc. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi Pasteur.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (1P30DK092950, UL1TR000448, KL2TR000450); National Center for Advancing Translational Science (KL2TR002346, UL1TR002345); Agency for Healthcare Research and Quality (R24HS19455); National Cancer Institute (KM1CA156708)
1973-P: Deficiency of Protein Deacetylase Sirt3 Enhances Acetylation of Histone H3 and H4 as to Affect Glucose Metabolism through Regulation of Dipeptidyl Peptidase-4 in Mice
Authors: UTO ASUKA , MIYASHITA KAZUTOSHI 
Published: June 2019

Background: Sirt3 is a NAD-dependent deacetylase that regulates lipid metabolism in mice and is related to longevity through modification of epigenome. Sirt3-deficient knockout (KO) mice fed a high-fat diet have been shown to develop obesity and metabolic syndrome-like phenotype. However, the precise mechanism by which they cause glucose intolerance has not been known. To reveal the regulatory mechanism of glucose metabolism through Sirt3, the metabolic parameters in the Sirt3-KO mice were examined.
Objective and Methods: The histone acetylation levels in various organs of the Sirt3-KO mice were examined by immunostaining of acetylated histone H3 (H3Ac) and H4 (H4Ac). Blood glucose levels in the Sirt3-KO mice after glucose loading were examined, associated with blood glucagon-like peptide-1 (GLP-1) levels and dipeptidyl peptidase-4 (DPP-4) activity. Gene expressions which were associated with the expressions and functions of GLP-1 and DPP-4 were quantified by qPCR.
Results: The Sirt3-KO mice were subjected to an oral glucose tolerance test (OGTT), together with an intraperitoneal glucose tolerance test (ipGTT). OGTT revealed an increase in the blood glucose levels in the KO mice, although ipGTT did not show the increase after the glucose loading. The blood GLP-1 and insulin levels decreased, and the DPP-4 activity increased significantly in the KO mice. qPCR analysis revealed a predominance of Sirt3 expression in the intestinal tract in the wild type mice. The immunostaining of H3Ac and H4Ac showed enhanced intensity in the small intestine and colon, and in the vascular endothelial cells in the KO mice.
Conclusion: These results suggest that Sirt3 deficiency impairs the incretin effect by a suppression of the blood GLP-1 levels and causes glucose intolerance. Enhanced acetylation of histone H3 and H4 in the KO mice might relate to the increase in the DPP-4 activity, which lead to the decrease in the GLP-1 levels.

Disclosure
A. Uto: None. K. Miyashita: Research Support; Self; Johnson & Johnson, Merck & Co., Inc., Novo Nordisk Inc.
1975-P: Increased Pancreatic a Cell Ca2+ Oscillations Explain Hyperglucagonemia in High-Fat Diet-Fed Mice
Authors: KELLARD JOELY , BRIANT LINFORD , KNUDSEN JAKOB G. , RORSMAN PATRIK 
Published: June 2019

Glucagon secretion from pancreatic α cells is elevated in obesity, exacerbating hyperglycaemia and contributing to the development of diabetes. α cells exhibit intracellular calcium (Ca2+i) oscillations, which drive glucagon secretion. To understand these oscillations and their contribution (if any) to the diabetic phenotype, we developed a mouse model for studying α cell Ca2+i, and used this to investigate α cell Ca2+i dynamics in mice exposed to a high fat diet (HFD).
Mice expressing GCaMP3 specifically in α-cells (GcgCre x GCaMP3 reporter mouse) were fed a control (10% fat; CTL) or high fat diet (60%; HFD) for 12 weeks. Mice then underwent a glucose tolerance test (GTT). Ca2+i imaging and glucagon secretion experiments were carried out on isolated (ex vivo) islets.
HFD mice had impaired glucose tolerance compared to CTL mice (p&lt;0.0001, n=25 mice). Plasma glucagon was suppressed by high glucose in CTL (p=0.01), but not HFD mice (p=0.65; n=10-20 mice). In islets from both CTL and HFD mice, Ca2+i oscillation frequency was suppressed by high glucose (p&lt;0.0001 n=200-250 cells, 6 islets, 3 mice). However, oscillation frequency was higher in HFD mice vs. CTL (p&lt;0.0001; n= 203-252 cells, 6-9 islets, 3 mice). Oscillation amplitude was not altered by glucose in CTL or HFD mice (p=0.076 and 0.87 respectively, 31-67 cells, 6-7 islets, 3 mice). Pharmacological approaches suggested that the increase in oscillation frequency was not due to altered α cell fat metabolism (p=0.5 38-68 cells, 4 islets, 3 mice). Insulin secretion from ex vivo islets was elevated in HFD vs. CTL mice, although this did not reach significance (p=0.084; N=6 mice).
These preliminary data suggest that hyperglucagonemia in HFD mice may have origins intrinsic to the islet. This was not due to reduced paracrine regulation by insulin, as insulin secretion was elevated in HFD mice. Future experiments will aim to fully power this study and understand whether α cell intrinsic mechanisms contribute to the hyperglucagonemic phenotype.

Disclosure
J. Kellard: None. L. Briant: None. J.G. Knudsen: None. P. Rorsman: None.

Funding
UK Wellcome Trust