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Articles 1 - 30 of 38
Full-Text Articles in Endocrine System Diseases
Economy Smart Watch Fails To Accurately Monitor Blood Glucose Among Healthy Adults, Thinh Le Mr., Douglas Oberlin Dr., Adam Mohan Mr.
Economy Smart Watch Fails To Accurately Monitor Blood Glucose Among Healthy Adults, Thinh Le Mr., Douglas Oberlin Dr., Adam Mohan Mr.
Undergraduate Research
Monitoring and maintenance of blood glucose (BG) concentrations is of critical importance to individuals with diabetes mellitus. However, this often requires multiple finger-sticks and a glucometer, or the use of a prescription continuous glucose monitor (CGM). Recently, some smart watches have become available which claim to non-invasively monitor BG. This should not be confused with watches that pair with CGMs. The purpose of this study was to assess whether the economy smart watches were capable of detecting BG changes among healthy individuals. Currently three participants have completed this study. Healthy young adults reported to the lab after a 4-6 hour …
Effect Of Vitamin K Supplementation On Insulin Resistance: A Review, Samantha Mccord, Rebecca Willier, Kaitlyn Kirby, Kaylin Mahoney, Lance Dillon, Rileigh Rahrig, Brianna Lu, Joshua Honaker, Emily Eddy
Effect Of Vitamin K Supplementation On Insulin Resistance: A Review, Samantha Mccord, Rebecca Willier, Kaitlyn Kirby, Kaylin Mahoney, Lance Dillon, Rileigh Rahrig, Brianna Lu, Joshua Honaker, Emily Eddy
Pharmacy and Wellness Review
Insulin resistance is one of the pathological hallmarks that leads to the development of type II diabetes mellitus (T2DM). Around 40% of people aged 18 to 44 living in the United States have insulin resistance. Recent research, coupled with a better understanding of how vitamin K functions in the body, suggests that this vitamin could potentially help reduce insulin resistance. Vitamin K is not included in the American Diabetes Association (ADA) guidelines for the treatment of insulin resistance, but it has been shown to have some benefits in patients with T2DM. It may also serve as a treatment option for …
An Estrogen Receptor Α-Derived Peptide Improves Glucose Homeostasis During Obesity, Wanbao Yang, Wen Jiang, Wang Liao, Hui Yan, Weiqi Ai, Quan Pan, Wesley A Brashear, Yong Xu, Ling He, Shaodong Guo
An Estrogen Receptor Α-Derived Peptide Improves Glucose Homeostasis During Obesity, Wanbao Yang, Wen Jiang, Wang Liao, Hui Yan, Weiqi Ai, Quan Pan, Wesley A Brashear, Yong Xu, Ling He, Shaodong Guo
Faculty, Staff and Students Publications
Estrogen receptor α (ERα) plays a crucial role in regulating glucose and energy homeostasis during type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain incompletely understood. Here we find a ligand-independent effect of ERα on the regulation of glucose homeostasis. Deficiency of ERα in the liver impairs glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies reveal that ERα promotes hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediates the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we identify a peptide based on ERα 1-280 domain and find that ERα-derived peptide …
Cardiovascular Disease Management With Sodium-Glucose Cotransporter-2 Inhibitors In Patients With Type 2 Diabetes: A Cardiology Primer, Allan Zhang, Ramsey Kalil, Alexander Marzec, Stephanie A Coulter, Salim Virani, Kershaw V Patel, Matthew W Segar
Cardiovascular Disease Management With Sodium-Glucose Cotransporter-2 Inhibitors In Patients With Type 2 Diabetes: A Cardiology Primer, Allan Zhang, Ramsey Kalil, Alexander Marzec, Stephanie A Coulter, Salim Virani, Kershaw V Patel, Matthew W Segar
Faculty, Staff and Students Publications
Patients with type 2 diabetes face an elevated risk of cardiovascular disease. This review centers on sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that, according to a growing body of evidence, may have major potential for managing cardiovascular disease in patients with type 2 diabetes. This review presents findings from multiple clinical trials suggesting that SGLT2 inhibitors can not only serve as preventive therapeutic agents but also play a role in the active management of heart failure. The discussion includes the mechanism of action of SGLT2 inhibitors, emphasizing that they enhance urinary glucose excretion, which could lead to improved …
Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin
Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin
Faculty, Staff and Students Publications
BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.
OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.
METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …
Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Ying Han, Jiehui Jiang, Alzheimer’S Disease Neuroimaging Initiative
Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Ying Han, Jiehui Jiang, Alzheimer’S Disease Neuroimaging Initiative
Faculty, Staff and Student Publications
Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in …
Implementation Of A Pilot Quality Improvement Project To Guide The Administration Of Intraoperative Dexamethasone For Postoperative Nausea And Vomiting Prophylaxis In Patients With Diabetes Undergoing Orthopedic Procedures, Brittany W. Hall
Graduate Theses, Dissertations, and Problem Reports (ETD)
Background: At a local tertiary care hospital, there was no recommendation to guide anesthesia providers in the administration of intraoperative dexamethasone to patients with diabetes. While dexamethasone is a highly effective antiemetic, it may promote hyperglycemia in patients with diabetes.
Purpose: The purpose of this project was to guide and educate about current recommendations for the administration of dexamethasone for PONV prophylaxis in patients with diabetes.
Intervention: 1) Examined pre-intervention practices of dexamethasone administration. 2) Educated about current and best practices to anesthesia staff. 3) Developed badge buddy cards outlining the guideline. 4) Examined post-intervention practices. 5) Evaluated the effect …
Approaches To Estimate Bidirectional Causal Effects Using Mendelian Randomization With Application To Body Mass Index And Fasting Glucose, Jinhao Zou, Rajesh Talluri, Sanjay Shete
Approaches To Estimate Bidirectional Causal Effects Using Mendelian Randomization With Application To Body Mass Index And Fasting Glucose, Jinhao Zou, Rajesh Talluri, Sanjay Shete
Faculty, Staff and Student Publications
Mendelian randomization (MR) is an epidemiological framework using genetic variants as instrumental variables (IVs) to examine the causal effect of exposures on outcomes. Statistical methods based on unidirectional MR (UMR) are widely used to estimate the causal effects of exposures on outcomes in observational studies. To estimate the bidirectional causal effects between two phenotypes, investigators have naively applied UMR methods separately in each direction. However, bidirectional causal effects between two phenotypes create a feedback loop that biases the estimation when UMR methods are naively applied. To overcome this limitation, we proposed two novel approaches to estimate bidirectional causal effects using …
Alignment Between 24-H Light-Dark And Activity-Rest Rhythms Is Associated With Diabetes And Glucose Metabolism In A Nationally Representative Sample Of American Adults, Qian Xiao, John Durbin, Cici Bauer, Chris Ho Ching Yeung, Mariana G Figueiro
Alignment Between 24-H Light-Dark And Activity-Rest Rhythms Is Associated With Diabetes And Glucose Metabolism In A Nationally Representative Sample Of American Adults, Qian Xiao, John Durbin, Cici Bauer, Chris Ho Ching Yeung, Mariana G Figueiro
Faculty, Staff and Student Publications
OBJECTIVE: The alignment between environmental stimuli (e.g., dark, light) and behavior cycles (e.g., rest, activity) is an essential feature of the circadian timing system, a key contributor to metabolic health. However, no previous studies have investigated light-activity alignment in relation to glycemic control in human populations.
RESEARCH DESIGN AND METHODS: The analysis included ∼7,000 adults (aged 20-80 years) from the National Health and Nutrition Examination Survey (NHANES) (2011-2014) with actigraphy-measured, multiday, 24-h activity and light data. We used phasor analysis to derive phasor magnitude and phasor angle, which measures coupling strength and phase difference between the activity-rest and light-dark cycles, …
The Prevalence Of Diabetes In Juveniles, Tatyana Johnson
The Prevalence Of Diabetes In Juveniles, Tatyana Johnson
Graduate Student Dissertations, Theses, Capstones, and Portfolios
Diabetes mellitus, simply known as diabetes, is a metabolic disorder that impacts how the body makes use of glucose or blood sugar. Glucose is the primary supply of energy for the body’s cells, which is controlled by insulin, a pancreatic hormone. Diabetes results in high blood glucose levels (hyperglycemia), which are caused by either insufficient insulin production by the pancreas or ineffective insulin utilization by the body (Dean & McEntyre, 2004). Although there are several types of diabetes, the two main types are type 1 and type 2. Type 1, also known as juvenile diabetes, is an inflammatory condition in …
Anoctamin 4 Channel Currents Activate Glucose-Inhibited Neurons In The Mouse Ventromedial Hypothalamus During Hypoglycemia, Longlong Tu, Jonathan C Bean, Yang He, Hailan Liu, Meng Yu, Hesong Liu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Kristine M Conde, Mengjie Wang, Yongxiang Li, Bing Feng, Peiyu Gao, Zhao-Lin Cai, Makoto Fukuda, Mingshan Xue, Qingchun Tong, Yongjie Yang, Lan Liao, Jianming Xu, Chunmei Wang, Yanlin He, Yong Xu
Anoctamin 4 Channel Currents Activate Glucose-Inhibited Neurons In The Mouse Ventromedial Hypothalamus During Hypoglycemia, Longlong Tu, Jonathan C Bean, Yang He, Hailan Liu, Meng Yu, Hesong Liu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Kristine M Conde, Mengjie Wang, Yongxiang Li, Bing Feng, Peiyu Gao, Zhao-Lin Cai, Makoto Fukuda, Mingshan Xue, Qingchun Tong, Yongjie Yang, Lan Liao, Jianming Xu, Chunmei Wang, Yanlin He, Yong Xu
Faculty, Staff and Student Publications
Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood …
Vitamin B2 Enables Regulation Of Fasting Glucose Availability, Peter M Masschelin, Pradip Saha, Scott A Ochsner, Aaron R Cox, Kang Ho Kim, Jessica B Felix, Robert Sharp, Xin Li, Lin Tan, Jun Hyoung Park, Liping Wang, Vasanta Putluri, Philip L Lorenzi, Alli M Nuotio-Antar, Zheng Sun, Benny Abraham Kaipparettu, Nagireddy Putluri, David D Moore, Scott A Summers, Neil J Mckenna, Sean M Hartig
Vitamin B2 Enables Regulation Of Fasting Glucose Availability, Peter M Masschelin, Pradip Saha, Scott A Ochsner, Aaron R Cox, Kang Ho Kim, Jessica B Felix, Robert Sharp, Xin Li, Lin Tan, Jun Hyoung Park, Liping Wang, Vasanta Putluri, Philip L Lorenzi, Alli M Nuotio-Antar, Zheng Sun, Benny Abraham Kaipparettu, Nagireddy Putluri, David D Moore, Scott A Summers, Neil J Mckenna, Sean M Hartig
Faculty, Staff and Students Publications
Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrophy. In our study, depleting FAD pools in mice with a vitamin B2-deficient diet (B2D) caused phenotypes associated with organic acidemias and other IEMs, including reduced body weight, hypoglycemia, and fatty liver disease. Integrated discovery approaches revealed B2D tempered fasting activation of target genes for the nuclear receptor PPARα, including those required for gluconeogenesis. We also found …
Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez
Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez
Faculty, Staff and Student Publications
AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.
METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping …
Diabetes Technology Meeting 2022, Jingtong Huang, Andrea M Yeung, Ashley Y Dubord, Howard Wolpert, Peter G Jacobs, Wei-An Lee, Andjela Drincic, Elias K Spanakis, Jennifer L Sherr, Priya Prahalad, Alexander Fleming, Victoria C Hsiao, Tejaswi Kompala, Rayhan A Lal, Maya Fayfman, Barry H Ginsberg, Rodolfo J Galindo, Andreas Stuhr, J Geoffrey Chase, Bijan Najafi, Umesh Masharani, Jane Jeffrie Seley, David C Klonoff
Diabetes Technology Meeting 2022, Jingtong Huang, Andrea M Yeung, Ashley Y Dubord, Howard Wolpert, Peter G Jacobs, Wei-An Lee, Andjela Drincic, Elias K Spanakis, Jennifer L Sherr, Priya Prahalad, Alexander Fleming, Victoria C Hsiao, Tejaswi Kompala, Rayhan A Lal, Maya Fayfman, Barry H Ginsberg, Rodolfo J Galindo, Andreas Stuhr, J Geoffrey Chase, Bijan Najafi, Umesh Masharani, Jane Jeffrie Seley, David C Klonoff
Center on Aging Staff Publications
Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 3 to November 5, 2022. Meeting topics included (1) the measurement of glucose, insulin, and ketones; (2) virtual diabetes care; (3) metrics for managing diabetes and predicting outcomes; (4) integration of continuous glucose monitor data into the electronic health record; (5) regulation of diabetes technology; (6) digital health to nudge behavior; (7) estimating carbohydrates; (8) fully automated insulin delivery systems; (9) hypoglycemia; (10) novel insulins; (11) insulin delivery; (12) on-body sensors; (13) continuous glucose monitoring; (14) diabetic foot ulcers; (15) the environmental impact of diabetes technology; and (16) spinal …
Early Postpartum Hba1c After Hyperglycemia First Detected In Pregnancy-Imperfect But Not Without Value, Ankia Coetzee, David R Hall, Mari Van De Vyver, Magda Conradie
Early Postpartum Hba1c After Hyperglycemia First Detected In Pregnancy-Imperfect But Not Without Value, Ankia Coetzee, David R Hall, Mari Van De Vyver, Magda Conradie
Faculty, Staff and Student Publications
BACKGROUND: South African women of childbearing age are disproportionally affected by obesity and at significant risk of Type 2 Diabetes Mellitus (T2DM). Unless pregnant, they do not readily undergo screening for T2DM. With a local focus on improved antenatal care, hyperglycemia is often first detected in pregnancy (HFDP). This may erroneously be attributed to Gestational Diabetes Mellitus (GDM) in all without considering T2DM. Glucose evaluation following pregnancy is essential for early detection and management of women with T2DM in whom persistent hyperglycemia is to be expected. Conventional testing with an oral glucose tolerance test (OGTT) is cumbersome, prompting investigation for …
Relationships Among Biochemical Measures In Children With Diabetic Ketoacidosis, Nicole S Glaser, Michael J Stoner, Maria Y Kwok, Kimberly S Quayle, Kathleen M Brown, Jeff E Schunk, Jennifer L Trainor, Julie K Mcmanemy, Leah Tzimenatos, Arleta Rewers, Lise E Nigrovic, Jonathan E Bennett, Sage R Myers, Mckenna Smith, T Charles Casper, Nathan Kuppermann
Relationships Among Biochemical Measures In Children With Diabetic Ketoacidosis, Nicole S Glaser, Michael J Stoner, Maria Y Kwok, Kimberly S Quayle, Kathleen M Brown, Jeff E Schunk, Jennifer L Trainor, Julie K Mcmanemy, Leah Tzimenatos, Arleta Rewers, Lise E Nigrovic, Jonathan E Bennett, Sage R Myers, Mckenna Smith, T Charles Casper, Nathan Kuppermann
Faculty, Staff and Students Publications
OBJECTIVES: Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions.
METHODS: We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode.
RESULTS: pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). …
Cerebral Microdialysis And Glucopenia In Traumatic Brain Injury: A Review, Himanshu Sharma, John P Mcginnis, Katherine E Kabotyanski, Shankar P Gopinath, Jerry C Goodman, Claudia Robertson, Jovany Cruz Navarro
Cerebral Microdialysis And Glucopenia In Traumatic Brain Injury: A Review, Himanshu Sharma, John P Mcginnis, Katherine E Kabotyanski, Shankar P Gopinath, Jerry C Goodman, Claudia Robertson, Jovany Cruz Navarro
Faculty, Staff and Students Publications
Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such …
Predicting Insulin Pump Therapy Settings, Riccardo L. Ferraro, David Grijalva, Alex Trahan
Predicting Insulin Pump Therapy Settings, Riccardo L. Ferraro, David Grijalva, Alex Trahan
SMU Data Science Review
Millions of people live with diabetes worldwide [7]. To mitigate some of the many symptoms associated with diabetes, an estimated 350,000 people in the United States rely on insulin pumps [17]. For many of these people, how effectively their insulin pump performs is the difference between sleeping through the night and a life threatening emergency treatment at a hospital. Three programmed insulin pump therapy settings governing effective insulin pump function are: Basal Rate (BR), Insulin Sensitivity Factor (ISF), and Carbohydrate Ratio (ICR). For many people using insulin pumps, these therapy settings are often not correct, given their physiological needs. While …
Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 Regulates Hepatic Fuel Metabolism, Brittany A Stork, Adam Dean, Andrea R Ortiz, Pradip Saha, Nagireddy Putluri, Maricarmen D Planas-Silva, Iqbal Mahmud, Kimal Rajapakshe, Cristian Coarfa, Stefan Knapp, Philip L Lorenzi, Bruce E Kemp, Benjamin E Turk, John W Scott, Anthony R Means, Brian York
Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 Regulates Hepatic Fuel Metabolism, Brittany A Stork, Adam Dean, Andrea R Ortiz, Pradip Saha, Nagireddy Putluri, Maricarmen D Planas-Silva, Iqbal Mahmud, Kimal Rajapakshe, Cristian Coarfa, Stefan Knapp, Philip L Lorenzi, Bruce E Kemp, Benjamin E Turk, John W Scott, Anthony R Means, Brian York
Faculty, Staff and Students Publications
OBJECTIVE: The liver is the primary internal metabolic organ that coordinates whole body energy homeostasis in response to feeding and fasting. Genetic ablation or pharmacological inhibition of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) has been shown to significantly improve hepatic health and peripheral insulin sensitivity upon overnutrition with high fat diet. However, the precise molecular underpinnings that explain this metabolic protection have remained largely undefined.
METHODS: To characterize the role of CaMKK2 in hepatic metabolism, we developed and challenged liver-specific CaMKK2 knockout (CaMKK2
RESULTS: Consistent with previous findings, we show that hepatic CaMKK2 ablation significantly improves indices of peripheral insulin …
Maladaptive Positive Feedback Production Of Chrebpβ Underlies Glucotoxic Β-Cell Failure, Liora S Katz, Gabriel Brill, Pili Zhang, Anil Kumar, Sharon Baumel-Alterzon, Lee B Honig, Nicolás Gómez-Banoy, Esra Karakose, Marius Tanase, Ludivine Doridot, Alexandra Alvarsson, Bennett Davenport, Peng Wang, Luca Lambertini, Sarah A Stanley, Dirk Homann, Andrew F Stewart, James C Lo, Mark A Herman, Adolfo Garcia-Ocaña, Donald K Scott
Maladaptive Positive Feedback Production Of Chrebpβ Underlies Glucotoxic Β-Cell Failure, Liora S Katz, Gabriel Brill, Pili Zhang, Anil Kumar, Sharon Baumel-Alterzon, Lee B Honig, Nicolás Gómez-Banoy, Esra Karakose, Marius Tanase, Ludivine Doridot, Alexandra Alvarsson, Bennett Davenport, Peng Wang, Luca Lambertini, Sarah A Stanley, Dirk Homann, Andrew F Stewart, James C Lo, Mark A Herman, Adolfo Garcia-Ocaña, Donald K Scott
Faculty, Staff and Students Publications
Preservation and expansion of β-cell mass is a therapeutic goal for diabetes. Here we show that the hyperactive isoform of carbohydrate response-element binding protein (ChREBPβ) is a nuclear effector of hyperglycemic stress occurring in β-cells in response to prolonged glucose exposure, high-fat diet, and diabetes. We show that transient positive feedback induction of ChREBPβ is necessary for adaptive β-cell expansion in response to metabolic challenges. Conversely, chronic excessive β-cell-specific overexpression of ChREBPβ results in loss of β-cell identity, apoptosis, loss of β-cell mass, and diabetes. Furthermore, β-cell "glucolipotoxicity" can be prevented by deletion of ChREBPβ. Moreover, ChREBPβ-mediated cell death is …
An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan
An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan
Faculty, Staff and Students Publications
As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer …
Circadian Clock, Diurnal Glucose Metabolic Rhythm, And Dawn Phenomenon, Fei Peng, Xin Li, Fang Xiao, Ruxing Zhao, Zheng Sun
Circadian Clock, Diurnal Glucose Metabolic Rhythm, And Dawn Phenomenon, Fei Peng, Xin Li, Fang Xiao, Ruxing Zhao, Zheng Sun
Faculty, Staff and Students Publications
The circadian clock provides cue-independent anticipatory signals for diurnal rhythms of baseline glucose levels and glucose tolerance. The central circadian clock is located in the hypothalamic suprachiasmatic nucleus (SCN), which comprises primarily GABAergic neurons. The SCN clock regulates physiological diurnal rhythms of endogenous glucose production (EGP) and hepatic insulin sensitivity through neurohumoral mechanisms. Disruption of the molecular circadian clock is associated with the extended dawn phenomenon (DP) in type 2 diabetes (T2D), referring to hyperglycemia in the early morning without nocturnal hypoglycemia. The DP affects nearly half of patients with diabetes, with poorly defined etiology and a lack of targeted …
An Exercise-Inducible Metabolite That Suppresses Feeding And Obesity, Veronica L Li, Yang He, Kévin Contrepois, Hailan Liu, Joon T Kim, Amanda L Wiggenhorn, Julia T Tanzo, Alan Sheng-Hwa Tung, Xuchao Lyu, Peter-James H Zushin, Robert S Jansen, Basil Michael, Kang Yong Loh, Andrew C Yang, Christian S Carl, Christian T Voldstedlund, Wei Wei, Stephanie M Terrell, Benjamin C Moeller, Rick M Arthur, Gareth A Wallis, Koen Van De Wetering, Andreas Stahl, Bente Kiens, Erik A Richter, Steven M Banik, Michael P Snyder, Yong Xu, Jonathan Z Long
An Exercise-Inducible Metabolite That Suppresses Feeding And Obesity, Veronica L Li, Yang He, Kévin Contrepois, Hailan Liu, Joon T Kim, Amanda L Wiggenhorn, Julia T Tanzo, Alan Sheng-Hwa Tung, Xuchao Lyu, Peter-James H Zushin, Robert S Jansen, Basil Michael, Kang Yong Loh, Andrew C Yang, Christian S Carl, Christian T Voldstedlund, Wei Wei, Stephanie M Terrell, Benjamin C Moeller, Rick M Arthur, Gareth A Wallis, Koen Van De Wetering, Andreas Stahl, Bente Kiens, Erik A Richter, Steven M Banik, Michael P Snyder, Yong Xu, Jonathan Z Long
Children’s Nutrition Research Center Staff Publications
Exercise confers robust protection against obesity, type 2 diabetes, and other cardiometabolic diseases.1–5 However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear.6 Here we show that exercise stimulates production of Lac-Phe, a blood-borne signaling metabolite that suppresses feeding and obesity. Lac-Phe biosynthesis from lactate occurs in CNDP2+ cells including immune cells, epithelial cells, and mesenchymal stem cells localized to diverse organs. In diet-induced obese mice, pharmacological elevation of circulating Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and …
The Role Of Palmitoleic Acid In Regulating Hepatic Gluconeogenesis Through Sirt3 In Obese Mice, Xin Guo, Xiaofan Jiang, Keyun Chen, Qijian Liang, Shixiu Zhang, Juan Zheng, Xiaomin Ma, Hongmei Jiang, Hao Wu, Qiang Tong
The Role Of Palmitoleic Acid In Regulating Hepatic Gluconeogenesis Through Sirt3 In Obese Mice, Xin Guo, Xiaofan Jiang, Keyun Chen, Qijian Liang, Shixiu Zhang, Juan Zheng, Xiaomin Ma, Hongmei Jiang, Hao Wu, Qiang Tong
Faculty, Staff and Students Publications
Hepatic gluconeogenesis is a crucial process to maintain glucose level during starvation. However, unabated glucose production in diabetic patients is a major contributor to hyperglycemia. Palmitoleic acid is a monounsaturated fatty acid (16:1n7) that is available from dietary sources. Palmitoleic acid exhibits health beneficial effects on diabetes, insulin resistance, inflammation, and metabolic syndrome. However, the mechanism by which palmitoleate reduces blood glucose is still unclear. SIRT3 is a key metabolism-regulating NAD+-dependent protein deacetylase. It is known that fasting elevates the expression of SIRT3 in the liver and it regulates many aspects of liver’s response to nutrient deprivation, such as fatty …
Paraventricular Vitamin D Receptors Are Required For Glucose Tolerance In Males But Not Females, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Gabrielle Phillips, Yanlin He, Stephanie Sisley
Paraventricular Vitamin D Receptors Are Required For Glucose Tolerance In Males But Not Females, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Gabrielle Phillips, Yanlin He, Stephanie Sisley
Faculty, Staff and Students Publications
When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice's paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance …
Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli
Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli
Faculty, Staff and Students Publications
Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …
Plasma Diaphanous Related Formin 1 Levels Are Associated With Altered Glucose Metabolism And Insulin Resistance In Patients With Polycystic Ovary Syndrome: A Case Control Study, Xing Li, Mingyu Liao, Jiaqing Shao, Weixin Li, Liu Shi, Dong Wang, Juan Ni, Qiuyue Shen, Fan Yang, Guiliang Peng, Ling Zhou, Yuling Zhang, Zheng Sun, Hongting Zheng, Min Long
Plasma Diaphanous Related Formin 1 Levels Are Associated With Altered Glucose Metabolism And Insulin Resistance In Patients With Polycystic Ovary Syndrome: A Case Control Study, Xing Li, Mingyu Liao, Jiaqing Shao, Weixin Li, Liu Shi, Dong Wang, Juan Ni, Qiuyue Shen, Fan Yang, Guiliang Peng, Ling Zhou, Yuling Zhang, Zheng Sun, Hongting Zheng, Min Long
Faculty, Staff and Students Publications
BACKGROUND: Diaphanous related formin 1 (DIAPH1) is a novel component of advanced glycation end product (AGE) signal transduction that was recently found to participate in diabetes-related disorders, obesity, and androgen hormones. We investigated whether plasma DIAPH1 levels were a potential prognostic predictor for polycystic ovary syndrome (PCOS).
METHODS: The levels of circulating plasma DIAPH1 and indicators of glucose, insulin, lipid metabolism, liver enzymes, kidney function, sex hormones, and inflammation were measured in 75 patients with PCOS and 77 healthy participants. All of the participants were divided into normal-weight (NW) and overweight/obese (OW) subgroups. Statistical analyses were performed with R studio. …
A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington
A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington
Faculty, Staff and Students Publications
Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …
Relationship Between Estimated Average Glucose (Eag) And Fasting Plasma Glucose In A Cohort Of Pakistani Diabetic Subjects, Nanik Ram, Sibtain Ahmed, Saadia Sattar, Saira Furqan, Najmul Islam
Relationship Between Estimated Average Glucose (Eag) And Fasting Plasma Glucose In A Cohort Of Pakistani Diabetic Subjects, Nanik Ram, Sibtain Ahmed, Saadia Sattar, Saira Furqan, Najmul Islam
Section of Diabetes, Endocrinology and Metabolism
Introduction: Scientific literature is scarce on the utility of estimated average glucose (eAG) from Pakistan. Hence, there is a dire need to evaluate the relationship between eAG and fasting plasma glucose (FPG), in order to enhance our understanding of eAG and its usefulness. This study aims to investigate the relationship between FPG and eAG in diabetic patients calculated using HbA1C.
Materials and methods: A retrospective study was conducted at the Aga Khan University, Karachi, Pakistan. The medical records of both genders in the age range of 18-60 years, presenting as outpatients at the endocrine clinic, labeled as DM, were reviewed …
Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Na Li, Mingyang Huang, Mason Bartels, Sophie Dogné, Shangang Zhao, Xi Chen, Clair Crewe, Leon Straub, Lavanya Vishvanath, Zhuzhen Zhang, Mengle Shao, Yongjie Yang, Christy M Gliniak, Ruth Gordillo, Gordon I Smith, William L Holland, Rana K Gupta, Bingning Dong, Nathalie Caron, Yong Xu, Yucel Akgul, Samuel Klein, Philipp E Scherer
Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Na Li, Mingyang Huang, Mason Bartels, Sophie Dogné, Shangang Zhao, Xi Chen, Clair Crewe, Leon Straub, Lavanya Vishvanath, Zhuzhen Zhang, Mengle Shao, Yongjie Yang, Christy M Gliniak, Ruth Gordillo, Gordon I Smith, William L Holland, Rana K Gupta, Bingning Dong, Nathalie Caron, Yong Xu, Yucel Akgul, Samuel Klein, Philipp E Scherer
Faculty, Staff and Students Publications
Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma …