Endocrine System Diseases Commons^™

Identification Of Small-Molecule Inhibitors Of The Salmonella Frab Deglycase Using A Live-Cell Assay, Anice Sabag-Daigle, Erin F Boulanger, Pankajavalli Thirugnanasambantham, Jamison D Law, Alex J Bogard, Edward J Behrman, Venkat Gopalan, Brian M M Ahmer

Faculty, Staff and Student Publications

Nontyphoidal salmonellosis is one of the most significant foodborne diseases in the United States and globally. There are no vaccines available for human use to prevent this disease, and only broad-spectrum antibiotics are available to treat complicated cases of the disease. However, antibiotic resistance is on the rise and new therapeutics are needed. We previously identified the Salmonella fraB gene, that mutation of causes attenuation of fitness in the murine gastrointestinal tract. The FraB gene product is encoded in an operon responsible for the uptake and utilization of fructose-asparagine (F-Asn), an Amadori product found in several human foods. Mutations in …

Hypoglycemia: A Mimic Of Global Ischemic Injury, Zachary Leavitt, Jay Babu, Sannah Vasaya, Robert Balsinger, Aroucha Vickers

Annual Research Symposium

No abstract provided.

Hepatocytes Demarcated By Ephb2 Contribute To The Progression Of Nonalcoholic Steatohepatitis, Yang Xiao, Kirill Batmanov, Wenxiang Hu, Kun Zhu, Alexander Y Tom, Dongyin Guan, Chunjie Jiang, Lan Cheng, Sam J Mccright, Eric C Yang, Matthew R Lanza, Yifan Liu, David A Hill, Mitchell A Lazar

Faculty, Staff and Students Publications

Current therapeutic strategies for treating nonalcoholic steatohepatitis (NASH) have failed to alleviate liver fibrosis, which is a devastating feature leading to hepatic dysfunction. Here, we integrated single-nucleus transcriptomics and epigenomics to characterize all major liver cell types during NASH development in mice and humans. The bifurcation of hepatocyte trajectory with NASH progression was conserved between mice and humans. At the nonalcoholic fatty liver (NAFL) stage, hepatocytes exhibited metabolic adaptation, whereas at the NASH stage, a subset of hepatocytes was enriched for the signatures of cell adhesion and migration, which were mainly demarcated by receptor tyrosine kinase ephrin type B receptor …

Genome-Wide Screening Reveals The Genetic Basis Of Mammalian Embryonic Eye Development, Justine M Chee, Louise Lanoue, Dave Clary, Kendall Higgins, Lynette Bower, Ann Flenniken, Ruolin Guo, David J Adams, Fatima Bosch, Robert E Braun, Steve D M Brown, H-J Genie Chin, Mary E Dickinson, Chih-Wei Hsu, Michael Dobbie, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D Heaney, Yann Herault, Martin Hrabe De Angelis, Fabio Mammano, Lauryl M J Nutter, Helen Parkinson, Chuan Qin, Toshi Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, Brian Brooks, Colin Mckerlie, K C Kent Lloyd, Henrik Westerberg, Ala Moshiri

Faculty, Staff and Students Publications

BACKGROUND: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways …

Energy Intake At The Intersection Of The Clock And Ageing, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

Circadian Clock And Temporal Meal Pattern, Xin Li, Zheng Sun

Faculty, Staff and Students Publications

The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses, with a low glycemic response but a high satiety/thermogenic response to meals consumed at waking compared to other time points. Consistently, studies show that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome, compared to consuming identical meals at dinner. Conversely, breakfast skipping or/and late dinner can have unfavorable metabolic outcomes. It remains controversial how meal frequency affects metabolic health. In contrast, irregular meals, especially irregular breakfasts, show consistent adverse metabolic …

Psychosocial, Medical, And Demographic Variables Associated With Parent Mealtime Behavior In Young Children Recently Diagnosed With Type 1 Diabetes, Caroline Gonynor, Christine Wang, Carrie Tully, Maureen Monaghan, Randi Streisand, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: Managing young children's mealtime concerns can be challenging after type 1 diabetes (T1D) diagnosis because of developmental factors and diabetes management demands. To identify potential intervention targets, we evaluated medical, psychosocial, and demographic factors in relation to parents' engagement in problem mealtime behaviors (e.g., pressure to eat, restriction).

METHOD: Parents (N = 157) of young children (age 1-6 years) reported on psychosocial variables (parent fear of hypoglycemia, family functioning, parent problem solving, and parents' problem mealtime behavior frequency and perceptions of being problematic) within 2 months after T1D diagnosis. Hierarchical regression analyses examined associations among psychosocial variables, demographics (child …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Interfering With Lipid Metabolism Through Targeting Ces1 Sensitizes Hepatocellular Carcinoma For Chemotherapy, Gang Li, Xin Li, Iqbal Mahmud, Jazmin Ysaguirre, Baharan Fekry, Shuyue Wang, Bo Wei, Kristin L Eckel-Mahan, Philip L Lorenzi, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, …

Adar1 Deletion Causes Degeneration Of The Exocrine Pancreas Via Mavs-Dependent Interferon Signaling, Dhwani N Rupani, Fredrik I Thege, Vidhi Chandra, Hajar Rajaei, Robert W Cowan, Sonja M Wörmann, Olivereen Le Roux, Prerna Malaney, Sara L Manning, Jack Hashem, Jennifer Bailey-Lundberg, Andrew D Rhim, Florencia Mcallister

Faculty, Staff and Student Publications

Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional RNA processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role of Adar1 in pancreatic development and homeostasis, we conditionally deleted Adar1 from the murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due to malabsorption associated with exocrine pancreatic insufficiency. Analyses of pancreata revealed ductal cell expansion, heightened interferon-stimulated gene expression and an increased influx of immune cells. Concurrent deletion of Adar1 and Mavs, a …

Bcl2l11 Induction Mediates Sensitivity To Src And Mek1/2 Inhibition In Thyroid Cancer, Madison M Rose, Veronica L Espinoza, Katelyn J Hoff, Laura A Pike, Vibha Sharma, Marie-Claude Hofmann, Aik Choon Tan, Nikita Pozdeyev, Rebecca E Schweppe

Faculty, Staff and Student Publications

Patients with advanced thyroid cancer, including advanced papillary thyroid cancer and anaplastic thyroid cancer (ATC), have low survival rates because of the lack of efficient therapies available that can combat their aggressiveness. A total of 90% of thyroid cancers have identifiable driver mutations, which often are components of the MAPK pathway, including BRAF, RAS, and RET-fusions. In addition, Src is a non-receptor tyrosine kinase that is overexpressed and activated in thyroid cancer, which we and others have shown is a clinically relevant target. We have previously demonstrated that combined inhibition of Src with dasatinib and the MAPK …

Qualitative Study Of Pathways To Care Among Adults With Diabetes In Rural Guatemala, Anita Nandkumar Chary, Meghna Nandi, David Flood, Scott Tschida, Katharine Wilcox, Sophie Kurschner, Pablo Garcia, Peter Rohloff

Faculty, Staff and Students Publications

OBJECTIVE: The burden of diabetes mellitus is increasing in low-income and middle-income countries (LMICs). Few studies have explored pathways to care among individuals with diabetes in LMICs. This study evaluates care trajectories among adults with diabetes in rural Guatemala.

DESIGN: A qualitative investigation was conducted as part of a population-based study assessing incidence and risk factors for chronic kidney disease in two rural sites in Guatemala. A random sample of 807 individuals had haemoglobin A1c (HbA1c) screening for diabetes in both sites. Based on results from the first 6 months of the population study, semistructured interviews were performed with 29 …

Vitamin D Enhanced Vitamin D Receptor (Vdr) Inhibition Of Nlrp3 Inflammasome Activation Can Attenuate The Development Of Autoimmune Thyroiditis, Alexzon Mandac

Capstone Showcase

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disease affecting approximately 2% of the population. Characterized by the gradual loss of thyroid function through an autoimmune attack on the thyroid gland, the disease manifests symptoms that negatively affect one’s quality of life. The mechanisms behind the disease’s pathophysiology are not fully understood; however, researchers are examining the involvement of the NLRP3 inflammasome in the disease. This thesis will address the question of whether Vitamin D can act as an inhibitor of the NLRP3 inflammasome and attenuate the progression of AIT in mouse model. Current investigations explore the effects of NLRP3 inhibition …

The Short- And Long-Term Readmission Of Four Major Categories Of Digestive System Cancers: Does Obesity Or Metabolic Disorder Matter?, Yan Li, Xiaoqin Wu, Yongfeng Song, Peipei Wang, Bofei Zhang, Bingzhou Guo, Ziwei Liu, Yafei Wu, Shanshan Shao, Yiping Cheng, Honglin Guo, Xiude Fan, Jiajun Zhao

Faculty, Staff and Student Publications

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.

Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox …

Receptor-Interacting Protein 1 And 3 Kinase Activity Are Required For High-Fat Diet Induced Liver Injury In Mice, Xiaoqin Wu, Rakesh K Arya, Emily Huang, Megan R Mcmullen, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND: The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical role for MLKL, the key effector regulating necroptosis, but not RIP3, in mediating high fat diet-induced liver injury in mice. RIP1 and RIP3 have active N-terminus kinase domains essential for activation of MLKL and subsequent necroptosis. However, little is known regarding domain-specific roles of RIP1/RIP3 kinase in liver diseases. Here, we hypothesized that RIP1/RIP3 kinase activity are required for the development of high fat diet-induced liver injury.

METHODS:Rip1K45A/K45A and Rip3K51A/K51A kinase-dead mice on a C57BL/6J background and their littermate …

School-Based Intervention Impacts Availability Of Vegetables And Beverages In Participants’ Homes, Erin A Hudson, Marissa Burgermaster, Sophia M Isis, Matthew R Jeans, Sarvenaz Vandyousefi, Matthew J Landry, Rebecca Seguin-Fowler, Joya Chandra, Jaimie Davis

Faculty, Staff and Student Publications

As rates of metabolic syndrome rise, children consume too few vegetables and too much added sugar. Because children tend to eat what is available at home, the home environment plays a key role in shaping dietary habits. This secondary analysis evaluated the effects of a school-based gardening, cooking, and nutrition education intervention (TX Sprouts) compared to control on the availability of vegetables, fruit juice, and sugar-sweetened beverages (SSBs) at home. In the TX Sprouts cluster-randomized trial, 16 schools were randomized to TX Sprouts (

Review Article: New Treatments For Advanced Differentiated Thyroid Cancers And Potential Mechanisms Of Drug Resistance, Sarah Hamidi, Marie-Claude Hofmann, Priyanka C Iyer, Maria E Cabanillas, Mimi I Hu, Naifa L Busaidy, Ramona Dadu

Faculty, Staff and Student Publications

The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in …

Examining The Effects Of Hyperglycemia On Retinal Regeneration, Emmanuella Ec Kyllians

Theses and Dissertations--Biology

Diabetes is a disease that affects how the body processes glucose, leading to a cascade of other complications, one of which is diabetic retinopathy (DR). DR is a neurovascular disease that affects the retina and research has revealed the role of retinal neurodegeneration in its development. Animal models like zebrafish have emerged as important tools for studying the molecular and cellular mechanisms underlying DR. On the other hand, retinitis pigmentosa (RP) is a degenerative disease that involves the progressive degeneration of rods and cones, and hyperglycemia has been found to impair regeneration. Therefore, this study aims to examine the effects …

Editorial: Metabolic Regulation Under Oxidative Stress In Cancer, Elavarasan Subramani, Abishai Dominic, Pratip K Bhattacharya, Daniel E Frigo, Ilya Bederman, Ali Vaziri-Gohar

Faculty, Staff and Student Publications

Oxidative stress has emerged as a key component of cancer metabolism that impacts multiple facets of tumor biology (1). Recent studies have shed light on the complex interplay of cellular redox and its impact on molecular mechanisms that govern metabolic reprogramming under oxidative stress (2, 3). It is well established that altered glucose metabolism exhibited by tumor cells leads to an enormous oxidative burden through various metabolic routes (4, 5). What is less known but remains a great interest to the field is whether elevated oxidative stress has a causal role in …

Pregnancy And Diabetic Ketoacidosis: Fetal Jeopardy And Windows Of Opportunity, Ankia Coetzee, David R Hall, Eduard J Langenegger, Mari Van De Vyver, Magda Conradie

Faculty, Staff and Student Publications

BACKGROUND: Diabetic ketoacidosis (DKA) during pregnancy poses significant risks to both the mother and fetus, with an increased risk of fetal demise. Although more prevalent in women with Type I diabetes (T1D); those with Type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) can also develop DKA. A lack of information about DKA during pregnancy exists worldwide, including in South Africa.

OBJECTIVE: This study examined the characteristics and outcomes associated with DKA during pregnancy.

METHODS: The study took place between 1 April 2020 and 1 October 2022. Pregnant women with DKA, admitted to Tygerberg Hospital's Obstetric Critical Care Unit (OCCU) …

Dysregulated Coagulation System Links To Inflammation In Diabetic Kidney Disease, Mengyun Xiao, Donge Tang, Shaodong Luan, Bo Hu, Wenyu Gong, Wolfgang Pommer, Yong Dai, Lianghong Yin

Faculty, Staff and Student Publications

Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease worldwide. Despite extensive research, the exact mechanisms responsible for its development remain incompletely understood. Notably, patients with diabetes and impaired kidney function exhibit a hypercoagulable state characterized by elevated levels of coagulation molecules in their plasma. Recent studies propose that coagulation molecules such as thrombin, fibrinogen, and platelets are interconnected with the complement system, giving rise to an inflammatory response that potentially accelerates the progression of DKD. Remarkably, investigations have shown that inhibiting the coagulation system may protect the kidneys in various animal models and clinical trials, suggesting …

Assessing The Most Vulnerable Subgroup To Type Ii Diabetes Associated With Statin Usage: Evidence From Electronic Health Record Data, Xinzhou Guo, Waverly Wei, Molei Liu, Tianxi Cai, Chong Wu, Jingshen Wang

Faculty, Staff and Student Publications

There have been increased concerns that the use of statins, one of the most commonly prescribed drugs for treating coronary artery disease, is potentially associated with the increased risk of new-onset Type II diabetes (T2D). Nevertheless, to date, there is no robust evidence supporting as to whether and what kind of populations are indeed vulnerable for developing T2D after taking statins. In this case study, leveraging the biobank and electronic health record data in the Partner Health System, we introduce a new data analysis pipeline and a novel statistical methodology that address existing limitations by (i) designing a rigorous causal …

Characteristics Of Type 2 Diabetes In Female And Male Youth, Beatriz Castillo Rodriguez, Marcela Astudillo, Mustafa Tosur, Ahmad Rafaey, Siripoom Mckay, Fida Bacha, Ashok Balasubramanyam, Maria J Redondo

Faculty, Staff and Students Publications

The incidence of type 2 diabetes in children is rising and carries a worse prognosis than in adults. The influence of sex on pediatric type 2 diabetes outcomes has not been well investigated. We studied 715 youth with type 2 diabetes diagnosed at a median age of 13.7 years and compared sex differences in demographic, clinical, and laboratory characteristics within the first year of diagnosis. Females diagnosed with type 2 diabetes were younger and at a higher stage of pubertal development than males, yet presented with lower A1Cs, a lower prevalence of diabetic ketoacidosis, and higher HDL cholesterol levels.

Indices Of Sarcopenic Obesity Are Important Predictors Of Finite Element Analysis-Derived Bone Strength In Older Adults With Obesity, Giulia Gregori, Arjun Paudyal, Yoann Barnouin, Alessandra Celli, Martha Belen Segoviano-Escobar, Reina Armamento-Villareal, Nicola Napoli, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

BACKGROUND: The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT).

METHODS: One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m

RESULTS: Both ALM/W and HGS were positively correlated explaining 28% …

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Students Publications

OBJECTIVE: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

RESEARCH DESIGN AND METHODS: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

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 …

Weight Strategy In Older Adults With Obesity: Calorie Restriction Or Not?, Georgia Colleluori, Dennis T Villareal

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Along with the marked increase in the population of older adults with obesity is the need for effective strategies to treat aging- and obesity-related complications. This review highlights recent progress in obesity management in older adults.

RECENT FINDINGS: Although calorie restriction is needed to significantly reduce fat mass, an exercise protocol is crucial to ameliorate functional outcomes. The addition of a resistance exercise protocol improves the response of muscle protein synthesis to anabolic stimuli, preventing the calorie restriction-induced reduction in muscle and bone mass. The addition of an aerobic exercise protocol improves cardiorespiratory fitness and cognitive function. …

Milder Loss Of Insulin-Containing Islets In Individuals With Type 1 Diabetes And Type 2 Diabetes-Associated Tcf7l2 Genetic Variants, Maria J Redondo, Sarah J Richardson, Daniel Perry, Charles G Minard, Alice L J Carr, Todd Brusko, Irina Kusmartseva, Alberto Pugliese, Mark A Atkinson

Faculty, Staff and Students Publications

AIMS/HYPOTHESIS: TCF7L2 variants are the strongest genetic risk factor for type 2 diabetes. In individuals with type 1 diabetes, these variants are associated with a higher C-peptide AUC, a lower glucose AUC during an OGTT, single autoantibody positivity near diagnosis, particularly in individuals older than 12 years of age, and a lower frequency of type 1 diabetes-associated HLA genotypes. Based on initial observations from clinical cohorts, we tested the hypothesis that type 2 diabetes-predisposing TCF7L2 genetic variants are associated with a higher percentage of residual insulin-containing cells (ICI%) in pancreases of donors with type 1 diabetes, by examining genomic data …

Nanocurcumin Combined With Insulin Alleviates Diabetic Kidney Disease Through P38/P53 Signaling Axis, Raghu Ganugula, Nikhil K Nuthalapati, Subhash Dwivedi, Dianxiong Zou, Meenakshi Arora, Richard Friend, David Sheikh-Hamad, Rita Basu, M N V Ravi Kumar

Faculty, Staff and Students Publications

Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but …