Endocrine System Diseases Commons^™

Type 2 Diabetes Subgroups, Risk For Complications, And Differential Effects Due To An Intensive Lifestyle Intervention, Michael P Bancks, Haiying Chen, Ashok Balasubramanyam, Alain G Bertoni, Mark A Espeland, Steven E Kahn, Scott Pilla, Elizabeth Vaughan, Lynne E Wagenknecht

Faculty, Staff and Students Publications

OBJECTIVE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.

RESEARCH DESIGN AND METHODS: In the Look AHEAD trial, 5,145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data on age …

Mitophagy Deficiency Increases Nlrp3 To Induce Brown Fat Dysfunction In Mice, Myoung Seok Ko, Ji Young Yun, In-Jeoung Baek, Jung Eun Jang, Jung Jin Hwang, Seung Eun Lee, Seung-Ho Heo, David A Bader, Chul-Ho Lee, Jaeseok Han, Jong-Seok Moon, Jae Man Lee, Eun-Gyoung Hong, In-Kyu Lee, Seong Who Kim, Joong Yeol Park, Sean M Hartig, Un Jung Kang, David D Moore, Eun Hee Koh, Ki-Up Lee

Faculty, Staff and Students Publications

Although macroautophagy/autophagy deficiency causes degenerative diseases, the deletion of essential autophagy genes in adipocytes paradoxically reduces body weight. Brown adipose tissue (BAT) plays an important role in body weight regulation and metabolic control. However, the key cellular mechanisms that maintain BAT function remain poorly understood. in this study, we showed that global or brown adipocyte-specific deletion of pink1, a Parkinson disease-related gene involved in selective mitochondrial autophagy (mitophagy), induced BAT dysfunction, and obesity-prone type in mice. Defective mitochondrial function is among the upstream signals that activate the NLRP3 inflammasome. NLRP3 was induced in brown adipocyte precursors (BAPs) from pink1 …

Acetyl-Coa And Metabolite Fluxes Regulate White Adipose Tissue Expansion, Jessica B Felix, Aaron R Cox, Sean M Hartig

Faculty, Staff and Students Publications

White adipose tissue (WAT) depends on coordinated regulation of transcriptional and metabolic pathways to respond to whole-body energy demands. We highlight metabolites that contribute to biosynthetic reactions for WAT expansion. Recent studies have precisely defined how byproducts of carbohydrate and lipid metabolism affect physiological and endocrine functions in adipocytes. We emphasize the critical emerging roles of short-chain fatty acids (SCFAs) and tricarboxylic acid (TCA) cycle metabolites that connect lipogenesis to WAT energy balance and endocrine functions. These insights address how adipocytes use small molecules generated from central carbon metabolism to measure responses to nutritional stress.

Diabetes In The Oncology Setting Webinar Series, Jennifer Williams, Denise A. Palma, Michael Rizk Msn, Aprn, Fnp-C, Bc-Adm

Education Week Poster Showcase 2021

Department of Endocrine Neoplasia and Hormonal Disorders

Thyroid Hormone Synthesis Continues Despite Biallelic Thyroglobulin Mutation With Cell Death, Xiaohan Zhang, Aaron P. Kellogg, Cintia E. Citterio, Hao Zhang, Dennis Larkin, Yoshiaki Morishita, Héctor M. Targovnik, Viviana A. Balbi, Peter Arvan

Pharmacy Faculty Articles and Research

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe …

In Men With Obesity, T2dm Is Associated With Poor Trabecular Microarchitecture And Bone Strength And Low Bone Turnover, Francesca Vigevano, Giulia Gregori, Georgia Colleluori, Rui Chen, Vimlin Autemrongsawat, Nicola Napoli, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

INTRODUCTION: Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

METHODS: Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically …

Pheochromocytoma Presenting As Testicular Pain: An Unusual Case Report, Jinal K. Patel, Varun Reddy, Gauthier L. Stepman, Debra Angelo, Johnathan Frunzi

Endocrinology

Pheochromocytoma (PCC) is a rare catecholamine-secreting tumor that arises from chromaffin cells of the adrenal medulla which are derived from the neural crest. This report illustrates a 51-year-old Caucasian male with a history of hypertension diagnosed two years ago who presented to the hospital due to acute onset of right testicular pain of 3-day duration. Laboratory results and imaging revealed a presumptive diagnosis of PCC. The patient had undergone robot-assisted laparoscopic right adrenalectomy 14 days after being diagnosed with PCC due to perioperative management with phenoxybenzamine. The final pathology report revealed a PCC. At follow-up two weeks after discharge, the …

Time To First Blood Glucose Determination And Administration Of Intravenous Glucose At Birth In Extremely Low Birth Weight Infants, Jihan Esmail, Ramasubbareddy Dhanireddy Md

Longitudinal Scholar's Project

Background: Extremely low birth weight (ELBW) infants are prone to hypoglycemia unless intravenous glucose is administered within an hour (golden hour) of life. These infants often require resuscitation at birth, but monitoring and intervention for hypoglycemia may be delayed.

Objectives: (1) Study the time to first blood glucose determination and IV glucose administration at birth in ELBW infants, (2) determine the incidence of hypoglycemia, <47mg/dl, and severe hypoglycemia, <40mg/dl, at admission, (3) determine risk factors for hypoglycemia, and (4) compare clinical outcomes at discharge between hypoglycemic and euglycemic infants.

Methods: 244 ELBW (≤1000g birth weight) infants born during Jan 2017- Feb 2020 at the Regional One Health NICU, Memphis, TN were included in the study. Data collected included maternal and infant clinical, demographic, and outcomes …

Hyperglycemia During The First Three Days Of Life Increases The Risk Of Retinopathy Of Prematurity In Extremely Low Birth Weight Infants, Jihan M. Esmail, Ramasubbareddy Dhanireddy Md

Longitudinal Scholar's Project

Background: The association between hyperglycemia and ROP has been inconsistent in previous studies. Extremely low birth weight (ELBW) infants are at high risk for ROP. They also experience hypoglycemia initially and hyperglycemia while receiving IV glucose infusion. The effect of initial hypoglycemia on hyperglycemia associated ROP risk is unknown.

Objective: To study the effect of initial hypoglycemia and subsequent hyperglycemia during the first three days of life on the incidence of ROP and severe ROP in ELBW (birth weight ≤1000g) infants.

Methods: Clinical and demographic data were collected from 227 ELBW infants born during the years 2017-2019 at the Regional …

Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun

Faculty, Staff and Students Publications

Systemic insulin sensitivity shows diurnal rhythm with a peak at wakening1,2. The molecular mechanism underlying such a temporal pattern is unclear. Here we demonstrate that nuclear receptors Rev-erbα/β in the GABAergic neurons in the suprachiasmatic nucleus (SCNGABA) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviors under the regular light-dark cycles. Rev-erb regulates the rhythmic expression of genes involved in neurotransmission in the SCN and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at wakening causes glucose intolerance, while restoration …

Loss Of Bone Morphogenetic Protein-Binding Endothelial Regulator Causes Insulin Resistance, Hua Mao, Luge Li, Qiying Fan, Aude Angelini, Pradip K Saha, Huaizhu Wu, Christie M Ballantyne, Sean M Hartig, Liang Xie, Xinchun Pi

Faculty, Staff and Students Publications

Accumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that …

Single-Cell Rna-Seq Analysis Reveals Compartment-Specific Heterogeneity And Plasticity Of Microglia, Junying Zheng, Wenjuan Ru, Jay R Adolacion, Michael S Spurgat, Xin Liu, Subo Yuan, Rommel X Liang, Jianli Dong, Andrew S Potter, S Steven Potter, Ken Chen, Rui Chen, Navin Varadarajan, Shao-Jun Tang

Faculty, Staff and Students Publications

Microglia are ubiquitous central nervous system (CNS)-resident macrophages that maintain homeostasis of neural tissues and protect them from pathogen attacks. Yet, their differentiation in different compartments remains elusive. We performed single-cell RNA-seq to compare microglial subtypes in the cortex and the spinal cord. A multi-way comparative analysis was carried out on samples from C57/BL and HIV gp120 transgenic mice at two, four, and eight months of age. The results revealed overlapping but distinct microglial populations in the cortex and the spinal cord. The differential heterogeneity of microglia in these CNS regions was further suggested by their disparity of plasticity in …

Patterns Of Abnormal Glucose Metabolism In Acromegaly And Impact Of Treatment Modalities On Glucose Metabolism, Sajjad A. Khan, Nanik Ram, Qamar Masood

Section of Diabetes, Endocrinology and Metabolism

Background: Chronic exposure to high levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) leads to metabolic complications, most importantly dysglycemia in the form of diabetes mellitus and pre-diabetes. Dysglycemia if diagnosed early in the course of the disease can decrease complications. Treatment modalities in the form of surgery and medical therapy have varied impacts on glucose metabolism.
Objective: To determine the frequency of diabetes mellitus, impaired glucose tolerance, and impaired fasting glucose in Pakistani patients with acromegaly and to establish the impact of the intervention (surgery/medical) on glucose metabolism.
Methods: This study was a retrospective review of …

Testosterone Therapy And Bone Quality In Men With Diabetes And Hypogonadism: Study Design And Protocol, Vittoria Russo, Georgia Colleluori, Rui Chen, Sanjay Mediwala, Clifford Qualls, Michael Liebschner, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes mellitus (T2D) is often accompanied by male hypogonadism and both conditions are associated with increased risk for fractures. Testosterone (T) has been shown to improve the bone health of hypogonadal men but has not been tested in patients who also have T2D in addition to low T. To date, there is no treatment that is specifically recommended for bone disease among patients with T2D. This study will evaluate the effect of T therapy on the bone health of male veterans with low T who also have T2D.

METHODS: This is a randomized double-blind placebo-controlled trial of …

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn, Grade Research Group

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Calcaneal Ultrasound And Its Relation To Dietary And Lifestyle Factors, Anthropometry, And Vitamin D Deficiency In Young Medical Students, Lena Jafri, Hafsa Majid, Sibtain Ahmed, Ghazala Naureen, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Background: Bone quality and peak bone mass are greatly affected by lifestyle factors. The objective of the study was to investigate the relationships between anthropometry, dietary and caloric intake, body composition measurements, physical activity, and vitamin D status with quantitative ultrasound-based bone parameters among medical students.
Methods: Both male and female medical college students were included in this study. A detailed questionnaire was administered, collecting clinical, dietary, physical activity information, physical examination details, including body mass index (BMI). Body composition (total body fat, total body water, muscle mass, mean visceral fat mass, basal metabolic rate, bone mass using a bioelectrical …

Highlights From Studies Presented At The American Heart Association Scientific Session 2020: Navigating New Roads In Prevention, Aliza Hussain, Mahmoud Al Rifai, Dhruv Mahtta, Jing Liu, Vardhmaan Jain, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF THE REVIEW: This review highlights late-breaking science presented at the American Heart Association Scientific Session 2020 that demonstrated advancements in preventative cardiology and introduced novel treatment approaches for the management of chronic kidney disease, type 2 diabetes, and/or heart failure.

RECENT FINDINGS: The studies reviewed include clinical trials that assessed the use of omecamtiv in the treatment of heart failure with reduced heart failure (GALACTIC-HF); effects of sotagliflozin in patients with diabetes and recent heart failure exacerbation; cardiovascular outcomes with the use of omega-3 carboxylic acids in patients with high vascular risk and atherogenic dyslipidemia (STRENGTH) and omega-3 …

Compliance Of Checking Hba1c In A Tertiary Care Hospital Of Pakistan, Abdul Aziz, Syed Ahsan Ali

Section of Diabetes, Endocrinology and Metabolism

Background and objectives: The prevalence of diabetes mellitus worldwide was 171 million one and half decade ago, while the prediction is 366 million patients by 2030 and more than 640 million people by 2040. HbA1c value represents average blood glucose over the past 2-3 months and accounts for both pre-prandial and post-prandial blood glucose levels. A link between HbA1c and diabetic complications has been confirmed. In general, patients with controlled diabetes mellitus should have at least biannual testing, while patients with uncontrolled diabetes mellitus or unmet glycemic targets should be tested every three months. The objective was to see compliance …

Actividades Profesionales Reservadas En Argentina: Orígenes Y Actualidad / Reserved Professional Activities In Argentina: Origins And Current Situation, Cintia E. Citterio, Héctor Targovnik

Pharmacy Faculty Articles and Research

En Argentina, la Ley de Educación Superior (LES; Ley 24.521, 1995) establece que hay profesiones cuyo ejercicio puede comprometer el interés público poniendo en riesgo de modo directo la salud, la seguridad, los derechos, los bienes o la formación de los habitantes, y las mismas están contempladas en el artículo 43 de la LES. Sólo aquellas actividades que realicen estos profesionales y que implican un riesgo rigurosamente directo, se denominan actividades profesionales reservadas. Pero… ¿Cuál es la diferencia entre actividades profesionales reservadas y alcances de los títulos? ¿Y cómo se establecen? El objetivo de este trabajo es analizar el significado …

A Gigantic Uterine Leiomyoma And Big Bilateral Adrenal Myelolipomas As A Result Of Untreated Congenital Adrenal Hyperplasia, Betty La, Celestine Tung, Eugene A Choi, Ha Nguyen

Faculty, Staff and Students Publications

INTRODUCTION: Patients with congenital adrenal hyperplasia (CAH) can present early with salt wasting, adrenal insufficiency, and hyperandrogenism. Late consequences as a result of untreated CAH are now rarely seen. We present a patient with a massive uterine leiomyoma and bilateral adrenal myelolipomas due to longstanding treatment noncompliance.

CASE REPORT: A female patient with CAH was treated with glucocorticoids until the age of 29 years when they stopped with the intention of identifying as a male. The patient then presented with abdominal pain and distension. Computed tomography images of the abdomen and pelvis revealed a 31 × 35 × 31-cm abdominal …

Identification Of Deep-Intronic Splice Mutations In A Large Cohort Of Patients With Inherited Retinal Diseases, Xinye Qian, Jun Wang, Meng Wang, Austin D Igelman, Kaylie D Jones, Yumei Li, Keqing Wang, Kerry E Goetz, David G Birch, Paul Yang, Mark E Pennesi, Rui Chen

Faculty, Staff and Students Publications

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort …

Hemoglobin A1c Threshold For Reduction In Bone Turnover In Men With Type 2 Diabetes Mellitus, Sabaa Joad, Elliot Ballato, Fnu Deepika, Giulia Gregori, Alcibiades Leonardo Fleires-Gutierrez, Georgia Colleluori, Lina Aguirre, Rui Chen, Vittoria Russo, Virginia Carolina Fuenmayor Lopez, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

BACKGROUND: Emerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D.

METHOD: A cross-sectional analysis of baseline data was obtained from 217 men, ages 35-65, regardless of the presence or absence of hypogonadism or …

The Bile Acid Induced Hepatokine Orosomucoid Suppresses Adipocyte Differentiation, Sung Ho Lee, Jong Min Choi, Sung Yun Jung, Aaron R Cox, Sean M Hartig, David D Moore, Kang Ho Kim

Faculty, Staff and Students Publications

Bile acids have recently emerged as key metabolic hormones with beneficial impacts in multiple metabolic diseases. We previously discovered that hepatic bile acid overload distally modulates glucose and fatty acid metabolism in adipose tissues to exert anti-obesity effects. However, the detailed mechanisms that explain the salutary effects of serum bile acid elevation remain unclear. Here, proteomic profiling identified a new hepatokine, Orosomucoid (ORM) that governs liver-adipose tissue crosstalk. Hepatic ORMs were highly induced by both genetic and dietary bile acid overload. To address the direct metabolic effects of ORM, purified ORM proteins were administered during adipogenic differentiation of 3T3-L1 cells …

Endmt Regulation By Small Rnas In Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress, Roberta Giordo, Yusra M A Ahmed, Hilda Allam, Salah Abusnana, Lucia Pappalardo, Gheyath K Nasrallah, Arduino Aleksander Mangoni, Gianfranco Pintus

Faculty, Staff and Student Publications

Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth …

To Determine The Efficacy Of Bilateral Inferior Petrosal Sinus Sampling In Differentiating Cushing Disease From Ectopic Cushing Syndrome, Muhammad Azeemuddin, Tanveer Ul Haq, Shahmeer Khan, Raza Sayani, Ayesha Shoukat Hussain, Rumaisa Khan

Department of Radiology

Management of endogenous Cushing syndrome is based on its aetiology. Increased Adrenocorticotropic Hormone (ACTH) levels are the most common cause of this disorder and, therefore, it is critical to determine the source of ACTH before further management. Dynamic post contrast MRI is currently the most common investigation implied to diagnose pituitary adenoma; however, it comes with the drawback of low specificity and high false positive results. Inferior petrosal sinus sampling (IPSS) is an established invasive procedure performed to differentiate central versus peripheral source of ACTH which, in turn, results in hypercortesolaemia. This is a series of 14 patients who underwent …

Adipocyte-Specific Ablation Of Pu1 Promotes Energy Expenditure And Ameliorates Metabolic Syndrome In Aging Mice, Ke Yun Chen, Alejandra De Angulo, Xin Guo, Aditya More, Scott A Ochsner, Eduardo Lopez, David Saul, Weijun Pang, Yuxiang Sun, Neil J Mckenna, Qiang Tong

Faculty, Staff and Students Publications

Objective: Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of the age-associated metabolic syndrome.

Methods: We generated mice with adipocyte-specific PU.1 knockout, assessed metabolic changes in young and older adult PU.1^fl/fl (control) and AdipoqCre PU.1^fl/fl (aPU.1KO) mice, including body weight, body composition, energy expenditure, and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.

Results: aPU.1KO mice have elevated energy …

The E3 Ligase Traf4 Promotes Igf Signaling By Mediating Atypical Ubiquitination Of Irs-1, Wenjuan Yu, Ramesh Singh, Zhao Wang, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Insulin-like growth factor (IGF) is a potent mitogen that activates the IGF receptor (IGFR)/insulin receptor substrate (IRS) axis, thus stimulating growth in normal cells and uncontrolled cell proliferation in cancer. Posttranslational modifications of IRS such as ubiquitination tightly control IGF signaling, and we previously identified IRS-1 as a potential substrate for the E3 ubiquitin ligase TRAF4 using an unbiased screen. Here we provide evidence that TRAF4-mediated ubiquitination of IRS-1 is physiologically relevant and crucial for IGF signal transduction. Through site-directed mutagenesis we found that TRAF4 promotes an atypical K29-linked ubiquitination at the C-terminal end of IRS-1. Its depletion abolishes AKT …

Mitochondrial Regulation Of Diabetic Kidney Disease, Daniel L Galvan, Koki Mise, Farhad R Danesh

Faculty, Staff and Students Publications

The role and nature of mitochondrial dysfunction in diabetic kidney disease (DKD) has been extensively studied. Yet, the molecular drivers of mitochondrial remodeling in DKD are poorly understood. Diabetic kidney cells exhibit a cascade of mitochondrial dysfunction ranging from changes in mitochondrial morphology to significant alterations in mitochondrial biogenesis, biosynthetic, bioenergetics and production of reactive oxygen species (ROS). How these changes individually or in aggregate contribute to progression of DKD remain to be fully elucidated. Nevertheless, because of the remarkable progress in our basic understanding of the role of mitochondrial biology and its dysfunction in DKD, there is great excitement …