bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI663 A Rare Case Of Igf-2 Induced Hypoglycemia Associated With Metastatic Colon Cancer
Authors: Mohd Mari Anwar Alshaakh , Varshney Aarushi , Sidhu Ashlee , Matos Moises , Kinaan Mustafa 
Published: October 2023

Abstract
Disclosure: A. Alshaakh Mohd Mari: None. A. Varshney: None. A. Sidhu: None. M. Matos: None. M. Kinaan: None.
Introduction: The diagnosis of hypoglycemia in patients without diabetes is uncommon and nonislet cell tumor hypoglycemia (NICTH) represent a minority of these cases. The most common mechanism is related to IGF-2 production from tumor cells. Case description: A 66-year-old man with a history of stage IV colon cancer presented to the hospital due to breathlessness while receiving chemotherapy (Bevacizumab plus FOLFOX4). He had partial colectomy and chemotherapy 3 years earlier but was recently found to have metastatic disease to the liver. A CT abdomen during hospitalization showed a 15 cm hepatic mass occupying the entire right hepatic lobe. Endocrinology was consulted due to persistent postprandial and fasting hypoglycemia despite dextrose infusion. He had no history of diabetes and denied taking any diabetes medications. Plasma blood glucose (BG) was noted to be 74 mg/dl (74-106) while on dextrose. An 8AM cortisol was checked to exclude adrenal insufficiency and was 8.08 mcg/dL (4.30-22.40). A 72 hour fast was done but discontinued at 8 hours when plasma BG dropped to 48 and patient became symptomatic. At the time C-peptide and Insulin levels were low &lt;0.05 ng/mL (0.48-5.05) and &lt;1.0 mU/L (3.0-25) respectively, with normal Beta-hydroxybutyrate (BHB) 1.1 mg/dL (0.2-2.8). At the end of the fast 1 mg of glucagon was administered and his BG increased to 112 mg/dl in 2 hrs. IGF-1 levels were undetectable &lt;15 ng/mL and IGF-2 levels were found to be 175 ng/mL. The IGF2:IG1 ratio was at 11 confirming IGF-2 mediated NICTH. Dexamethasone 10 mg daily was started, and BG were maintained &gt; 70mg/dl without dextrose infusion. Discussion: In approximately 50% of NICTH, the tumor is identified prior to the onset of hypoglycemia, but up to 50% of these patients may be asymptomatic despite hypoglycemia. Our patient had a known hepatic lesion and was minimally symptomatic despite very low BG. The mechanism for NICTH can include insulin secretion from the tumor, replacement of hepatic tissue and increased glucose utilization by the tumor, or most commonly, IGF-2 secretion. In the case of IGF-2 mediated hypoglycemia insulin, proinsulin, C-peptide, and β-hydroxybutyrate levels are low. An elevated IGF-2:IGF-1 ratio (&gt;10) confirms the diagnosis. The primary treatment is through surgical removal or debulking of the tumor. Neoadjuvant therapies such as radiation and chemotherapy may reduce occurrences of hypoglycemia, but only temporarily. Glucocorticoids may be used when the underlying malignancy cannot be treated.
Presentation: Friday, June 16, 2023
FRI664 The Impact Of Prediabetes Diagnosis On The Prevalence Of Postbariatric Hypoglycemia
Authors: Reshma Shariff Julia Rose , Funk Luke , Zaveri Aayush , Belt Davis Dawn 
Published: October 2023

Abstract
Disclosure: J.R. Shariff: None. L. Funk: None. A. Zaveri: None. D.B. Davis: None.
Bariatric surgery is not only a mainstay of obesity treatment, but it can result in remission of metabolic conditions, such as Type 2 diabetes. Post-operatively however, patients can develop postbariatric hypoglycemia (PBH), which is thought to be due to changes in insulin sensitivity and hypersecretion after eating. It has been suggested that prior type 2 diabetes can protect against PBH as decreased β-cell function prevents hyperinsulinemia. Patients with prediabetes may not have deterioration of β-cell function resulting in increased insulin production in response to glycemic excursion and subsequent hypoglycemia. The study aimed to assess the prevalence and severity of PBH in patients with prediabetes compared to those without prediabetes prior to bariatric surgery. We conducted a retrospective cohort study of patients 18 years and older who underwent either Roux-en-Y gastric bypass or sleeve gastrectomy between 2014 and 2021 and did not have a history of type 1 or type 2 diabetes mellitus at a single academic medical center. A history of PBH (hypoglycemia reported or documented after eating, symptoms of hypoglycemia, and resolution of symptoms after eating) and prediabetes (defined as A1c 5.7-6.4%, fasting glucose of 100-125mg/dL, or oral glucose tolerance testing with 2-hour glucose 140-199mg/dL) was determined based on medical record review. 14 patients developed PBH out of 539 (2.6%). 110 patients had prediabetes (20.4%). Of these 110 patients, 4 had PBH (3.6%). Of the 429 patients without prediabetes, 10 patients had PBH (2.3%). There was a greater post-operative weight loss, on average, in patients with PBH (19.5%) than in those without PBH (15.9%), although it should be noted that all PBH patients had Roux en Y gastric bypass. Interestingly, only 15% of the PBH population appeared to be on pharmacologic treatment, despite 21.5% being hospitalized or in the emergency room for hypoglycemic events. Most PBH patients (64.3%) developed symptoms between 1 to 3 years post-operatively, which is consistent with other studies on this topic. There was no association between prediabetes and PBH in our dataset (p=0.46), however our data set was quite small and it may be difficult to draw significant conclusions. A larger scale study done in a prospective manner would be useful for further research.
Presentation: Friday, June 16, 2023
OR12-06 Hypothalamic Adgrl1 Is A Potential Glucoreceptor Involved In Regulating Energy Balance, Glucose Homeostasis, And Leptin Sensitivity In Mice
Authors: Samuel Dennis J , Faniyan Tumininu S , Raza Muhammad U , Bathina Siresha , Chhabra Kavaljit H 
Published: October 2023

Abstract
Disclosure: D.J. Samuel: None. T.S. Faniyan: None. M.U. Raza: None. S. Bathina: None. K.H. Chhabra: None.
The hypothalamus regulates energy and glucose homeostasis by influencing glucose-stimulated insulin secretion, insulin sensitivity, and activating the hypoglycemia counterregulatory response. Although hypothalamic glucose transporters coupled with glucose metabolism are involved in mediating some of these effects, it is unknown whether a plasma membrane receptor that directly binds to glucose can contribute to hypothalamic glucose signaling. We used affinity chromatography and biotin-labeled glucose to enrich glucose-binding plasma membrane proteins/receptors in the mouse hypothalamus and then performed proteomic analyses. Adhesion G-protein Coupled Receptor L1 (Adgrl1) was a top candidate as a potential glucoreceptor. Therefore, we generated Adgrl1loxp/loxp mice to knockout Adgrl1 in the ventromedial hypothalamus (VMH; a region known for glucose sensing) using the Cre-Lox system to determine the role of Adgrl1VMH in glucose homeostasis, energy balance, and leptin sensitivity. We measured body weight, food intake, 6h fasting blood glucose and plasma insulin levels. We also determined leptin sensitivity in the Adgrl1VMH deficient mice. We observed that 24 weeks old male Adgrl1VMH deficient mice had higher (p&lt;0.05) body weight (49 ±3.6 vs 35 ±1.3 g), blood glucose (210 ±4 vs 180 ±5 mg/dl), plasma insulin levels (2.92 ±0.24 vs 1.63 ±0.09 ng/ml), and leptin levels (21.11 ±1.72 vs 8.38 ±0.80 ng/ml) compared to their control littermates. Hyperinsulinemia and hyperleptinemia persisted in the Adgrl1VMH knockout mice even when they were weight-matched to their littermate controls, indicating the direct role of Adgrl1VMH in regulating plasma insulin and leptin levels. Ovariectomy in female mice was necessary to unmask the effects of Adgrl1VMH deficiency on energy and glucose homeostasis. To assess acute leptin sensitivity, we injected Adgrl1VMH deficient mice and their littermate control mice with recombinant mouse leptin (5 mg/Kg, i.p., twice a day for two days), and monitored their body weight and food intake. Male Adgrl1VMH deficient mice were more susceptible (p&lt;0.05) to leptin mediated decrease in food intake (-1 ±0.1 vs -0.5 ±0.005, g/day; these values are relative to each group’s corresponding baseline food intake) than their littermate controls. Decrease in body weight was similar in both groups with this acute leptin treatment. These findings suggest that Adgrl1VMH is essential in regulating energy and glucose homeostasis in a sex-specific manner. Moreover, Adgrl1VMH contributes to leptin’s acute effects on food intake. Therefore, hypothalamic Adgrl1 could be a target to enhance leptin sensitivity in future therapies for treating type 2 diabetes and obesity.
Presentation: Friday, June 16, 2023
SAT033 Disruption Of GHR In “Middle Aged” Mice Enhances Insulin Sensitivity And Extends Male Lifespan
Authors: Duran-Ortiz Silvana , Owen List Edward , Young Jonathan A , Casey Mathes Samuel , Basu Reetobrata , BH Slama Yosri , Berryman Darlene E , Joseph Kopchick John 
Published: October 2023

Abstract
Disclosure: S. Duran-Ortiz: None. E.O. List: None. J.A. Young: None. S.C. Mathes: None. R. Basu: None. Y.B. Slama: None. D.E. Berryman: None.
Reduced growth hormone (GH) action has been shown to extend healthspan and lifespan in several organisms. In fact, mice and humans with a congenital disruption in the GH receptor (R) gene (GHRKO mice and patients with Laron Syndrome, respectively) have improved insulin sensitivity and are resistant to diabetes, cancer and age-associated cognitive decline. Importantly, the GHRKO mice hold the record for the longest-lived laboratory mice, with a lifespan one week shy of five years of age. GHRKO mice also show reduced markers of aging such as adipose tissue senescence and mTORC1 signaling in liver, kidney, heart and muscle. However, as GH action is required for normal growth and development, we and others have hypothesized that targeted inhibition of GH action at an adult age could be a potent method to extend healthy lifespan. To test this hypothesis and to elucidate how far in development would disruption of GHR extend healthy lifespan, our laboratory recently reported on two mouse lines with post-natal ablation of the GHR at a pubertal age (1.5 months - 1.5mGHRKO mice) and at mature-adult age (6 months - 6mGHRKO mice). We found that ablation of the GHR gene at both 1.5- and 6-months of age extends maximal and mean lifespan preferentially in females. Furthermore, 6mGHRKO mice showed improved oxidative stress resistance while males had improved insulin sensitivity and reduced cancer incidence. With these promising results, we believe that interventions to extend aging should be effective when administered later in life. In the current study, we disrupted the GHR in middle aged mice (12 months - 12mGHRKO mice) using the Cre-Lox system. We found that 12mGHRKO mice exhibit GH insensitivity (high serum GH and low IGF-1 levels), increased adipose tissue mass, reduced lean mass, minimal impact on body weight and length, improved insulin sensitivity and reduced glucose levels in males as well as decreased adipose tissue fibrosis in females compared to males. Moreover, despite the increased fat mass, motor coordination and strength as measured by rotarod and grip strength tests show no deficit in 12mGHRKO mice compared to the controls. Importantly, the male 12mGHRKO mice showed a preferential and significant lifespan extension compared to control mice. Collectively, our results indicate that not only does post-natal GHR disruption does not affect growth and development, but it also confers several crucial healthspan and lifespan advantages. Acknowledgements: This work is supported by the State of Ohio's Eminent Scholar Program, by NIH grant AG059779, by the American Federation for Aging Research (AFAR) and by the Diabetes Institute and by the AMVETS.
Presentation: Saturday, June 17, 2023
SAT037 Glucagon-like Peptide-1 Receptor Knockout Mice Do Not Compensate For The Lack Of Incretin Action By Increasing Glucose-dependent Insulinotropic Polypeptide Secretion
Authors: Douglas Galsgaard Katrine , Kissow Hannelouise , Smits Mark M , Juul Jens J 
Published: October 2023

Abstract
Disclosure: K.D. Galsgaard: None. H. Kissow: None. M.M. Smits: None. J.J. Juul: None.
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), secreted from the intestinal L-cells and K-cells, respectively, both enhance glucose-stimulated insulin secretion. This enhancement is referred to as the incretin effect. In the pancreatic islets of GIP receptor knockout mice, GLP-1 sensitivity may be increased. Conversely, deletion of the GLP-1 receptor has been shown to be compensated for by increased GIP secretion and action. This suggests a compensatory adaptation to loss of incretin signaling, via increased action/secretion of the remaining incretin hormone. To investigate this further, we subjected GLP-1 receptor knockout (Glp-1r-/-) mice and their wild-type littermates (Glp-1r+/+ mice) to an oral glucose tolerance test (2 g/kg body weight of glucose via oral gavage; OGTT) with subsequent measurement of plasma GIP concentrations. In separate experiments we measured pancreatic insulin, glucagon, somatostatin, and total GLP-1 concentrations in Glp-1r-/- and Glp-1r+/+ mice, and total GLP-1 and GIP concentrations in the duodenum and distal ileum were also measured. During the OGTT, we found a similar GIP secretion (total area under the curve (tAUC0-30min)) in Glp-1r-/- and Glp-1r+/+ mice (15,432±2,148 vs. 13,683±1,316 pg/mL×min, P=0.5, n≥7). Blood glucose concentrations (tAUC0-30min) were increased in Glp-1r-/- mice during the OGTT (523.9±27.4 vs. 429.1±21.2 mmol/L×min, P=0.02, n≥6). Extractable pancreatic hormone concentrations were similar in Glp-1r+/+ and Glp-1r-/- mice; insulin (284.3±11.4 vs. 303.6±32.4 pmol/g tissue, P=0.6, n≥8); glucagon (203.6±24.3 vs. 270.8±36.9 pmol/g tissue, P=0.2, n≥8); somatostatin (299.9±94.97 vs. 321.4±78.79 pmol/g tissue, P=0.9, n≥9); and total GLP-1 (30.9±8.5 vs. 20.2±4.0 pmol/g tissue, P=0.2, n≤8). In the duodenum, extractable GIP (175.0±29.6 vs. 177.3±10.8 pmol/g tissue, P&gt;0.9, n≥8) and GLP-1 (57.5±35.6 vs. 28.9±3.2 pmol/g tissue, P=0.4, n≥9). In the distal ileum, extractable GIP (2.2±0.5 vs. 2.1±0.4 pmol/g tissue, P=0.8, n≥9) and GLP-1 (266.6±57.1 vs. 236.0±43.1, P=0.7, n≥9) concentrations were also similar in Glp-1r+/+ and Glp-1r-/- mice. In conclusion, our results do not support the notion that Glp-1r-/- mice compensate for the lack of GLP-1 receptor signaling by increasing glucose stimulated GIP secretion or by increasing the intestinal GIP content.
Presentation: Saturday, June 17, 2023
SAT039 Chronic Glucocorticoid Exposure Induced A S1PR2-Rorc Axis To Enhance Hepatic Gluconeogenesis
Authors: Arwyn Lee Rebecca , Chang Maggie , Tsay Ariel , Rim Lee Yeong , Li Danielle , Yiv Nicholas , Tian Sharon , Wang Jen-Chywan 
Published: October 2023

Abstract
Disclosure: R.A. Lee: None. M. Chang: None. A. Tsay: None. Y. Lee: None. D. Li: None. N. Yiv: None. S. Tian: None. J. Wang: None.
Glucocorticoids are steroid hormones whose circulating levels are elevated in response to stress to maintain metabolic homeostasis. Glucocorticoids are also used to treat inflammatory and autoimmune diseases due to their potent anti-inflammatory and immunomodulatory activities. However, chronic glucocorticoid treatment causes various metabolic disorders, such as hyperglycemia and insulin resistance. Glucocorticoids convey their functions through an intracellular glucocorticoid receptor (GR) which is a transcriptional regulator. While GR stimulates hepatic gluconeogenic gene transcription, additional mechanisms activated specifically by chronic glucocorticoid exposure can further enhance hyperglycemia. We found that chronic glucocorticoid exposure elevated hepatic production of sphingosine-1-phosphate (S1P) and hepatic knockdown of sphingosine-1-phosphate receptor 2 (S1PR2) attenuated chronic glucocorticoid-induced glucose intolerance and hepatic gluconeogenesis while having no effect on insulin signaling. Hepatic S1PR2 knockdown reduced GR occupancy on glucocorticoid response elements (GREs) of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (Pck1) and the catalytic subunit of glucose 6 phosphatase (G6pc), thus reducing their expressions. Interestingly, RAR-related orphan receptor C (Rorc) expression was reduced in the liver of glucocorticoid treated hepatic S1PR2 knockdown mice. We found that Rorc was also recruited to the promoter of Pck1 upon glucocorticoid treatment and reducing Rorc activity decreased the GR occupancy at the GRE of Pck1. In contrast, overexpressing Rorc in the liver of hepatic S1PR2 knockdown mice restored glucocorticoid-induced glucose intolerance, GR recruitment to GREs of gluconeogenic genes, and gluconeogenic gene expression. Overall, we propose that chronic glucocorticoid exposure induces a novel S1PR2-Rorc axis to promote the transcription of gluconeogenic genes to enhance hyperglycemia.
Presentation: Saturday, June 17, 2023
SAT040 Administration Of A DHCR24 Inhibitor Reduces The Excessive Adrenal Steroidogenesis In db/db Mice Through Effects The Alteration Of Intracellular Cholesterol Metabolism
Authors: Kamigaki Risa , Kameda Hiraku , Shibayama Yui , Nomoto Hiroshi , Cho KyuYong , Nakamura Akinobu , Jin Shigeki , Matoba Kotaro , Miyoshi Hideaki , Atsumi Tatsuya 
Published: October 2023

Abstract
Disclosure: R. Kamigaki: None. H. Kameda: None. Y. Shibayama: None. H. Nomoto: None. K. Cho: None. A. Nakamura: None. S. Jin: None. K. Matoba: None. H. Miyoshi: None. T. Atsumi: None.
Background and purpose: The circulating cortisol concentrations of patients with type 2 diabetes are high, suggesting that cortisol may be involved in diabetic complications. It has also been reported that the db/db mouse, a model of obesity and type 2 diabetes, has high circulating concentrations of steroid hormones. However, the mechanisms involved are unclear. In our previous study, we found that the expression of DHCR24, an enzyme that converts desmosterol (DES) to cholesterol (Chol) as part of de novo cholesterol synthesis, is upregulated in the adrenal glands of db/db mice. In the present study, we aimed to determine the effects of a DHCR24 inhibitor on adrenal steroidogenesis in db/db mice. Methods: Eight-week-old male db/db and db/+ mice were allocated to two groups, which were administered a weekly intraperitoneal injection of a DHCR24 inhibitor (U18666A; 10 mg/kg; (U) or PBS (P). Blood samples and their adrenal glands were collected 4 weeks later. We then compared the blood glucose, body mass, adrenal DES content, adrenal Chol content, and serum corticosterone (B) between the two groups. Sterols were extracted from adrenal tissue using the Folch method, and their concentrations were measured following picolinyl derivatization using liquid chromatography tandem-mass spectrometry. Results: There were no significant differences in the blood glucose concentrations or body masses of the P and U groups of both db/+ and db/db mice. The adrenal DES/adrenal mass ratio was higher in the db/db U group than in the db/db P group (db/db P vs. db/db U vs. db/+ P vs. db/+ U: 16.0±4.3 vs. 98.4±73.2 vs. 42.9±8.6 vs. 124.9±64.6 ng/mg, respectively; p&lt;0.05). The adrenal Chol/adrenal mass and serum B concentration were lower in the db/db U and db/+ P groups than in the db/db P group (db/db P vs. db/db U vs. db/+ P vs. db/+ U: 2.1±0.2 vs. 1.3±0.2 vs. 1.1±0.6 vs. 1.3±0.2 μg/mg; and 232.8±20.1 vs. 189.6±13.1 vs. 126.3±20.6 vs. 111.2±25.8 ng/mL; respectively; all p&lt;0.05). Conclusion: DHCR24 inhibition reduces cholesterol production and steroid hormone synthesis in the adrenal glands of db/db mice. This implies that the abnormal adrenal cholesterol metabolism in db/db mice plays a role in the greater adrenal steroidogenesis in type 2 diabetes, and that adrenal cholesterol metabolism may represent a novel therapeutic target for the affected patients.
Presentation: Saturday, June 17, 2023
SAT041 18F-FDG PET/CT Mapping Of Functional Microbial Niches To Understand Host Glucose Regulation After BCG Vaccinations
Authors: Dias Hans , Fu Jessie F , Luck Trevor G , Wolfe Grace E , Hostetter Emma , Ng Nathan C , Zheng Hui , Kühtreiber Willem , Price Julie C , Catana Ciprian , Faustman Denise L 
Published: October 2023

Abstract
Disclosure: H. Dias: None. J.F. Fu: None. T.G. Luck: None. G.E. Wolfe: None. E. Hostetter: None. N.C. Ng: None. H. Zheng: None. W. Kühtreiber: None. J.C. Price: None. C. Catana: None. D.L. Faustman: None.
Diverse microbiomes in humans are known to change host energy metabolism. When the bacillus Calmette-Guérin (BCG) vaccine, which consists of live but avirulent Mycobacterium bovis, is introduced as experimental therapy into human hosts with underlying type 1 diabetes (T1D), the BCG bacillus has been shown to gradually shift energy metabolism in host blood lymphoid cells from oxidative phosphorylation to aerobic glycolysis. Aerobic glycolysis draws more glucose out of the blood to fuel intracellular metabolism, and it may underlie the BCG bacillus’ therapeutic benefit: the systemic and long-term reduction of excess glucose from the blood of TID patients. The organ-specific niches where the BCG bacillus similarly alters metabolism and establishes persistent residence are not known. In a human clinical trial, we mapped the organ(s) niches for BCG-induced shift to aerobic glycolysis using fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and x-ray computed tomography (CT). This technique allowed us to reveal quantitatively, by Standardized Uptake Value Ratios, the organs with heightened glucose uptake in T1D participants (n=6) over a 2-year time-period after BCG vaccination versus before vaccination, as well as confirm earlier work that BCG vaccination gradually lowers blood sugar levels without any contribution from endogenous insulin. We also tested BALB/c mice (n=17) for the direct presence of BCG colonies in particular organ niches before and after vaccination. Results from both human and murine studies of the BCG microorganism concurred that the major anatomic site of functional metabolic change and residence is the spleen. The BCG bacillus also transiently mapped to the bone marrow, liver, circulating lymphocytes as in the descending aorta, and the lungs. Findings from human and murine studies support the spleen as the niche for the BCG vaccine’s functional improvement of metabolism. The spleen is significant because it is a lymphoid organ massive enough to explain BCG’s systemic benefit of lowering blood sugar to near normal levels in T1D.
Presentation: Saturday, June 17, 2023