Endocrine System Diseases Commons^™

Gating Of The Polycystin Ion Channel Signaling Complex In Neurons And Kidney Cells, Patrick Delmas, Surya Nauli, Xiaogang Li, Bertrand Coste, Nancy Osorio, Marcel Crest, David Brown, Jing Zhou

David C. Brown

Mutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders and multiple extrarenal (including brain) disease phenotypes. PC2, a member of the transient receptor potential channel superfamily, and PC1, an orphan membrane receptor of largely unknown function, are thought to be part of a common signaling pathway. Here, we show that in rat sympathetic neurons and kidney cells, coassembly of full-length PC1 with PC2 forms a plasmalemmal ion channel signaling complex in which PC1 stimulation simultaneously activates PC2 ion channels and G(i/o)-proteins. PC2 activation occurs through a structural rearrangement of PC1, independent of G-protein activation. …

Prescribing Patterns Of Metformin In High-Risk Patients With Prediabetes, Daniel Stirling, Ifeanyi Onor, Daniel Sarpong, Kristi Isaac Rapp, Lori Crawford

Ifeanyi Onor, PharmD, BCPS

Mifepristone Utilization In Cushing’S From Large Bilateral Adrenal Adenoma Prior To Surgery, Vasudev Magaji, Sarah Park, Katie Mastoris, Maura Bucciarelli, Scott Beman

Vasudev G Magaji MD, MS

Utilization of mifepristone was described to mitigate hypercortisolism from bilateral adrenal Cushing’s syndrome. A 47-year-old female on abdominal pain evaluation with CT was found to have a 5.4 × 1.7 × 4.9 cm right adrenal nodule and a 4.3 × 2.9 × 3.3 cm left adrenal nodule with calcification on CT scan with each having density of -3 Housefield units. She had hypercortisolism with testing revealing high urine free cortisol, unsuppressed cortisol on 1 mg and 8 mg overnight dexamethasone suppression testing, high 11 pm salivary cortisol × 2 along with elevated random cortisol and undetectable ACTH. Her DHEA-S, plasma …

Elevated Serum Glucose Levels And Survival After Acute Heart Failure: A Population-Based Perspective, Benjamin Helfand, Nicholas Maselli, Darleen Lessard, Jorge Yarzebski, Joel Gore, David Mcmanus, Jane Saczynski, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Limited data are available about the characteristics, treatment and survival in patients without diabetes mellitus (DM), previously diagnosed DM and patients with hyperglycaemia who present with acute decompensated heart failure (ADHF). Our objectives were to examine differences in these endpoints in patients hospitalized with ADHF. METHODS: Patients hospitalized with ADHF during 1995, 2000, 2002 and 2004 comprised the study population. RESULTS: A total of 5428 non-diabetic patients were hospitalized with ADHF, 3807 with diagnosed DM and 513 with admission hyperglycaemia. Patients with admission hyperglycaemia experienced the highest in-hospital death rates (9.9%) compared to those with diagnosed DM (6.5%) and …

Association Between Chlorinated Pesticides In The Serum Of Prepubertal Russian Boys And Longitudinal Biomarkers Of Metabolic Function, Jane Burns, Paige Williams, Susan Korrick, Russ Hauser, Oleg Sergeyev, Boris Revich, Thuy Lam, Mary Lee

Mary M. Lee

Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, beta-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass …

Response To Comment On: Goldberg Et Al. Circadian Variation In The Response To The Glucose Challenge Test In Pregnancy: Implications For Screening For Gestational Diabetes Mellitus. Diabetes Care 2012;35:1578-1584, Robert Goldberg, Chang Ye, Mathew Sermer, Philip Connelly, Anthony Hanley, Bernard Zinman, Ravi Retnakaran

Dr. Chang Ye

No abstract provided.

Type I Diabetes In Children And Vitamin D, Susan Flesher, Md

Susan L Flesher, MD

Decade-Long Trends In The Characteristics, Management And Hospital Outcomes Of Diabetic Patients With St-Segment Elevation Myocardial Infarction, Mayra Tisminetzky, Samuel Joffe, David Mcmanus, Chad Darling, Joel Gore, Jorge Yarzebski, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

PURPOSE: Our objectives were to describe recent trends in the characteristics and in-hospital outcomes in diabetic as compared with non-diabetic patients hospitalized with ST-segment elevation myocardial infarction (STEMI).

METHODS: We reviewed the medical records of 2537 persons with (n = 684) and without (n = 1853) a history of diabetes who were hospitalized for STEMI between 1997 and 2009 at 11 medical centres in Central Massachusetts.

RESULTS: Diabetic patients were more likely to be older, female and to have a higher prevalence of previously diagnosed comorbidities. Diabetic patients were more likely to have developed important in-hospital complications and to have …

Farm Residence And Reproductive Health Among Boys In Rural South Africa, Rene English, Melissa Perry, Mary Lee, Elaine Hoffman, Steven Delport, Mohamed Dalvie

Mary M. Lee

BACKGROUND: Few studies have investigated reproductive health effects of contemporary agricultural pesticides in boys. OBJECTIVES: To determine the association between pesticide exposure and reproductive health of boys. METHODS: We conducted a cross-sectional study in rural South Africa of boys living on and off farms. The study included a questionnaire (demographics, general and reproductive health, phyto-estrogen intake, residential history, pesticide exposures, exposures during pregnancy); and a physical examination that included sexual maturity development ratings; testicular volume; height, weight, body mass index; and sex hormone concentrations. RESULTS: Among the 269 boys recruited into the study, 177 (65.8%) were categorized as farm (high …

Diabetes Care Trends In The Ma Patient Centered Medical Home Initiative (Ma Pcmhi) At Mid-Point, Sai Cherala, Judith Steinberg, Stephen Baker

Sai Cherala

Background: The MA PCMHI is a multi-payer demonstration involving 45 primary care practices. Thirty-one (31) practices receive additional financial support; all receive technical assistance.

Objectives: To assess data trends in diabetes quality measures from participating adult practices.

Study Design: Quality improvement study utilizing practices’ self-reported data on clinical quality measures. Diabetes measures included blood pressure, LDL cholesterol and hemoglobin A1C control and depression screening.

Methods: Monthly quality data from 38 practices reported June 2011 (baseline) through November 2012 were evaluated. Using a general linear mixed model Analysis of Variance (ANOVA), an overall comparison across time and pair-wise comparisons between times …

Diabetic Rates And Mice Are Resistent To Porcine And Human Insulin: Flawed Experimental Models For Testing Islet Xenograft, A. Pepper, C. Gall, D. Mazzuca, C.W.J. Melling, D. White

Jamie Melling

BACKGROUND: Islet transplantation is potentially a promising therapy for the restoration of carbohydrate control to diabetic patients. However, the global application of islet transplantation requires a ubiquitous source of beta cells. The xenotransplantation of porcine islets would provide such a source. Success in porcine islet xenografting has been achieved in diabetic primates. However, there are few reports of reversal of diabetes with porcine islet xenografts in rodent models of diabetes, relative to the number of successful rodent experiments performed as allografts. Here we report for the first time the inability of porcine (and human) insulin to control blood glucose levels …

Myocardial Hsp70 Phosphorylation And Pkc-Mediated Cardioprotection Following Exercise, C.W. Melling, David Thorp, Kevin Milne, Earl Noble

Jamie Melling

Both protein kinase C (PKC) activation and Hsp70 expression have been shown to be key components for exercise-mediated myocardial protection during ischemia–reperfusion injury. Given that Hsp70 has been shown to undergo inducible phosphorylation in striated muscle and liver, we hypothesized that PKC may regulate myocardial Hsp70 function and subsequent exercise-conferred cardioprotection through this phosphorylation. Hence, acute exercise of male Sprague–Dawley rats (30 m/min for 60 min at 2% grade) was employed to assess the role of PKC and its selected isoforms in phosphorylation of Hsp70 and protection of the myocardium during ischemia-reperfusion injury. It was observed that administration of the …

Invited Review: Heat Shock Proteins And Exercise: A Primer, Earl Noble, Kevin Milne, C.W. Melling

Jamie Melling

Heat shock proteins (HSPs) are, in general, prosurvival molecules within the cellular environment, and the overexpression of even just 1 family of HSPs can lead to protection against and improvements after a variety of stressors. Not surprisingly, a fertile area of study has grown out of effors to exploit the innate biologic behaviour of HSPs. Exercise, because of the inherent physiologic stresses associated with it, is but 1 stimulus that can result in a robust increase in various HSPs in several tissues, not the least of which happen to be the heart and skeletal muscle. The purpose of this review …

Exercise-Mediated Regulation Of Hsp70 Gene Expression Following Exercise Training, C.W. Melling, David Thorp, Kevin Milne, Matthew Krause, Earl Noble

Jamie Melling

An issue central to understanding the biological benefits associated with regular exercise training is to elucidate the intracellular mechanisms governing exercise-conferred cardioprotection. Heat shock proteins (HSPs), most notably the inducible 70-kDa HSP family member Hsp70, are believed to participate in the protection of the myocardium during cardiovascular stress. Following acute exercise, activation of PKA mediates the suppression of an intermediary protein kinase, ERK1/2, which phosphorylates and suppresses the activation of the heat shock transcription factor 1 (HSF1). However, following exercise training, ERK1/2 has been reported to regulate the transcriptional activation of several genes involved in cell growth and proliferation and …

Pka-Mediated Erk1/2 Inactivation And Hsp70 Gene Expression Following Exercise, C.W. Melling, Matthew Krause, Earl Noble

Jamie Melling

Exercise induces the expression of the cardioprotective protein, Hsp70, through the activation of its transcription factor HSF1. Recently, we reported that administration of a protein kinase A (PKA) inhibitor suppressed exercise-induced hsp70 gene expression, suggesting a role for PKA in the regulation of HSF1 activation in vivo. While the mechanism by which PKA regulates HSF1 is unclear, studies in vitro have reported that HSF1 is phosphorylated on two serine residues by mitogen activated protein kinases (MAPKs); ERK1/2 (ser307) and JNK/SAPK (ser363). As PKA is a regulator of these protein kinases, the current study examined the role of PKA in their …

Castration Inhibits The Exercise-Induced Accumulation Of Hsp70 In Male Rodent Cardiac Muscle Tissue, Kevin Milne, David Thorp, C.W. Melling, Earl Noble

Jamie Melling

Intense exercise leads to accumulation of the inducible member of the 70-kDa family of heat shock proteins, Hsp70, in male, but not female, hearts. Estrogen is at least partially responsible for this difference. Because androgen receptors are expressed in the heart and castration leads to decreases in calcium regulatory proteins and altered cardiac function, testosterone (T) or its metabolites could also be involved. We hypothesized that removal of endogenous T production through castration would reduce cardiac Hsp70 accumulation after an acute exercise bout, whereas castrated animals supplemented with 5α-dihydrotestosterone (DHT) would show the intact male response. Fifty-four 8-wk-old male Sprague-Dawley …