Endocrine System Diseases Commons^™

Stat1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity In Obesity, Aaron R Cox, Natasha Chernis, David A Bader, Pradip K Saha, Peter M Masschelin, Jessica B Felix, Robert Sharp, Zeqin Lian, Vasanta Putluri, Kimal Rajapakshe, Kang Ho Kim, Dennis T Villareal, Reina Armamento-Villareal, Huaizhu Wu, Cristian Coarfa, Nagireddy Putluri, Sean M Hartig

Faculty, Staff and Students Publications

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1a-KO) enhanced mitochondrial function …

Mir-30a Targets Gene Networks That Promote Browning Of Human And Mouse Adipocytes, Pradip K Saha, Mark P Hamilton, Kimal Rajapakshe, Vasanta Putluri, Jessica B Felix, Peter Masschelin, Aaron R Cox, Mandeep Bajaj, Nagireddy Putluri, Cristian Coarfa, Sean M Hartig

Faculty, Staff and Students Publications

MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates that miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to antidiabetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced miR-30a levels and diminished expression of the canonical PPARγ target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, …

Metabolic Dysregulation In The Atp7b-/- Wilson's Disease Mouse Model, Clavia Ruth Wooton-Kee, Matthew Robertson, Ying Zhou, Bingning Dong, Zhen Sun, Kang Ho Kim, Hailan Liu, Yong Xu, Nagireddy Putluri, Pradip Saha, Cristian Coarfa, David D Moore, Alli M Nuotio-Antar

Faculty, Staff and Students Publications

Inactivating mutations in the copper transporter Atp7b result in Wilson’s disease. The Atp7b−/− mouse develops hallmarks of Wilson’s disease. The activity of several nuclear receptors decreased in Atp7b−/− mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b−/− mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography–mass spectrometry and correlated with transcriptomic data. Atp7b−/− mice fed a chow diet presented …

Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could …

Pediatric Type Ii Diabetes Mellitus: Examining The Upward Trend, Allison Foering

Senior Honors Theses

In recent years, there has been a significant increase in pediatric onset of type II diabetes. This paper will examine elements contributing to this trend. Type II diabetes will be discussed, including related pathophysiology, manifestations, diagnosis, and complications, with differentiation between adult and pediatric onset. Possible prevention and treatment methods appropriate for pediatric patients will also be discussed, along with possible outcomes in pediatric patients that could result from this disease. Overall, this paper will provide insight on the causes of this growing trend, and ways to improve the risks imposed on pediatric patients.

Ethnic Differences In Maternal Adipokines During Normal Pregnancy, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%). Serum adiponectin and resistin were measured at entry (week 16.8) and the 3rd trimester (week 30.7) using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African …

Type Ii Diabetes And Its Treatment, Gregory Mountain

Nursing Student Class Projects (Formerly MSN)

Approximately 28.9 million Americans have been diagnosed with type II diabetes (Jia-Haur Hu, Lin, Miller, Nguyen, & Nguyen, 2014). It is a disease that can cause or potentiate numerous comorbidities that negatively affects multiple body systems if left untreated (Jia-Haur Hu, et al., 2014). In 2012, the total estimated cost for treatment of type II diabetes in America was an astronomical $245 billion (Jia-Haur Hu, et al., 2014). Type II diabetes is a result of many cellular processes that lead to insulin resistance resulting in increased blood glucose levels (Jia-Haur Hu, et al., 2014). Treatments for type II diabetes include …

Incretin Hormones And Their Effects In Type 2 Diabetes, Molly Getz

Nursing Student Class Projects (Formerly MSN)

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized as having pancreatic β-cell dysfunction, insulin resistance and hyperglycemia (Stephens, 2010, p. 491). T2DM affected 29.1 million Americans or 9.3% of the population in 2012 and was the seventh leading cause of death in the United States in 2010 ("ADA Statistics," 2014), with many of these patients finding it difficult to achieve or maintain adequate glycemic control despite making lifestyle changes and pharmacologic interventions (Freeman, 2007). Disease management of T2DM requires a comprehensive plan including medication therapy, education and active involvement of the patient, with the goal of therapy to …

Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay

Physiology Faculty Publications

AIMS AND HYPOTHESIS: Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.

METHODS: Gem-deficient mice were generated and their metabolic phenotype characterised by in …

Polycystic Ovary Syndrome: Pathogenesis, Health Consequences, And Treatment Of Pcos In Relation To Insulin Resistance, Danielle Bernier

Honors Theses and Capstones

The purpose of this paper is to present a review of the current research on polycystic ovary syndrome (PCOS). PCOS is one of the most common endocrine disorders in women of reproductive age, affecting 5-10% of the population. Despite its prevalence, PCOS remains largely under unknown. This review has been broken down into two separate chapters. The first is the pathogenesis and related health consequences of PCOS. This chapter focuses on the diagnosis of PCOS as well as the prevalence and incidence of the disease. It then delves into the pathogenesis with a focus on genetics, obesity, insulin resistance and …

After Avandia: The Use Of Antidiabetic Drugs In Patients With Heart Failure, Khaled I Khalaf, Heinrich Taegtmeyer

The Texas Heart Institute Journal

Managing diabetes mellitus is an ongoing concern, especially in the presence of heart failure. Recent reports have drawn attention to adverse cardiovascular events associated with the use of thiazolidinediones, including rosiglitazone (Avandia). In 2011, the U.S. Food and Drug Administration implemented a stringent “restricted access program” for the prescription of Avandia. Other studies, which have revealed increased mortality rates in association with tight glycemic control, raise serious concerns about managing diabetes in heart-failure patients.

Herein, we provide a perspective on the management of noninsulin-dependent diabetes in patients with heart failure. We point out that thiazolidinediones exert their major effects through …