Endocrinology, Diabetes, and Metabolism Commons^™

Pkd1 Inhibits Ampk2 Through Phosphorylation Of Serine 491 And Impairs Insulin Signaling In Skeletal Muscle Cells, Kimberly A. Coughlan, Rudy J. Valentine, Bella S. Sudit, Katherine Allen, Yossi Dagon, Barbara B. Kahn, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

Background: Diminished activity of the enzyme AMP-activated protein kinase (AMPK) is associated with impaired insulin signaling.

Results: Protein Kinase (PK)C/D1 activation inhibits AMPK2 via Ser491 phosphorylation; PKD1 inhibition prevents this in skeletal muscle cells.

Conclusion: PKD1 is a novel upstream AMPK-kinase that phosphorylates AMPK on Ser491 and regulates insulin signaling.

Significance: PKD1 inhibition may be a novel strategy for improving insulin sensitivity.

Nutrient Excess And Ampk Downregulation In Incubated Skeletal Muscle And Muscle Of Glucose Infused Rats, Kimberly A. Coughlan, Thomas W. Balon, Rudy J. Valentine, Robert Petrocelli, Vera Schultz, Amana Brandon, Gregory J. Cooney, Edward W. Kraegen, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

We have previously shown that incubation for 1h with excess glucose or leucine causes insulin resistance in rat extensor digitorum longus (EDL) muscle by inhibiting AMP-activated protein kinase (AMPK). To examine the events that precede and follow these changes, studies were performed in rat EDL incubated with elevated levels of glucose or leucine for 30min-2h. Incubation in high glucose (25mM) or leucine (100μM) significantly diminished AMPK activity by 50% within 30min, with further decreases occurring at 1 and 2h. The initial decrease in activity at 30min coincided with a significant increase in muscle glycogen. The subsequent decreases at 1h were …

Whole Egg Consumption Impairs Insulin Sensitivity In Rat Model Of Obesity And Type 2 Diabetes, Cassondra J. Saande, Megan A. Steffes, Joseph L. Webb, Rudy J. Valentine, Matthew J. Rowling, Kevin Schalinske

Rudy Valentine

Background: The literature regarding the relation between egg consumption and type 2 diabetes (T2D) is inconsistent and there is limited evidence pertaining to the impact of egg consumption on measures of insulin sensitivity. Objective: The objective of this study was to investigate the effect of dietary whole egg on metabolic biomarkers of insulin resistance in T2D rats. Downloaded from https://academic.oup.com/cdn/advance-article-abstract/doi/10.1093/cdn/nzz015/5374517 by Iowa State University user on 28 March 2019 Methods: Male Zucker diabetic fatty rats (n=12; 6 wk of age) and their lean controls (n=12; 6 wk of age) were randomly assigned to a casein- or whole egg-based diet. At …

Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T. Sherpa, Rajasekharreddy Pala, Kimberly F. Atkinson, William J. Pearce, Lubo Zhang, Surya M. Nauli

Lubo Zhang, PhD

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to …

Discrepancies In Publications Related To Hmb-Fa And Atp Supplementation, Jeremy A. Gentles, Stuart M. Phillips

Jeremy A. Gentles

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Franklin D. Shuler

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K2 (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation of …

Prepubertal Organochlorine Pesticide Concentrations And Age Of Pubertal Onset Among Russian Boys, Thuy Lam, Paige Williams, Mary Lee, Susan Korrick, Linda Birnbaum, Jane Burns, Oleg Sergeyev, Boris Revich, Larisa Altshul, Donald Patterson, Wayman Turner, Russ Hauser

Mary M. Lee

BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to …

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 …

Physically Interactive Games Increase Vo2 Above Resting Metabolic Rate, Shaelee Allen, Jacob E. Barkley, Janet Dufek, Paul Hafen, Michael Jarrett, Krystina Moschella, James Navalta, Robert Rietjens, Richard Tandy, Antonio Santo

Jacob E Barkley

The purpose of this study was to determine the energy cost, beyond resting metabolic rate (RMR), of playing select games on the Nintendo Wii for 30 contiguous minutes. Physically interactive games (i.e. Basic Run and Basic Step) increase energy expenditure above resting values compared to a sedentary game (Tanks!) and therefore may help individual’s become more active. Furthermore, Basic Run and Basic Step elicited MET values of 3.9 and 3.2, respectively, which is considered moderate-intensity exercise and could be used to meet daily recommendations for physical activity.

Nonenzymatic Glycosylation Of Erythrocyte Membrane Proteins. Relevance To Diabetes, J A. Miller, Ellen M. Gravallese, H F. Bunn

Ellen M. Gravallese

Nonenzymatic glycosylation of proteins of the erythrocyte membrane was determined by incubating erythrocyte ghosts with [3H]borohydride. The incorporation of tritium into protein provides a reliable assay of ketoamine linkages. The membrane proteins from 18 patients with diabetes incorporated twice as much radioactivity as membrane proteins from normal erythrocytes. After acid hydrolysis, amino acid analysis showed that the majority of radioactivity was localized to glucosyllysine. Autoradiograms showed that all of the major proteins of the erythrocyte membrane, separated by electrophoresis on sodium dodecyl sulfate gels, contained ketoamine linkages. No protein bands in either normal or diabetic erythrocytes showed significant preferential labeling. …

Human Umbilical Cord Blood-Derived Mononuclear Cells Improve Murine Ventricular Function Upon Intramyocardial Delivery In Right Ventricular Chronic Pressure Overload, Saji Oommen, Satsuki Yamada, Susana Cantero Peral, Katherine A. Campbell, Elizabeth S. Bruinsma, Andre Terzic, Timothy J. Nelson

Katherine Campbell, PhD

No abstract provided.

Associations Of Adipose Tissue Architecture, Adipokines And Inflammatory Markers With Body Mass Index And Gestational Weight Gain In Non-Diabetic Pregnancies, Tiffany A. Moore Simas, Crina Boeras, Ningning Zhang, Olga Gaelikman, Katherine G. Leung, Nicole M. Wedick, Laura Robidoux, Jodi Adams Puleo, Mary M. Lee, Silvia Corvera, Milagros C. Rosal

Mary M. Lee

Background: Some pregnancy weight gain is stored as adipose tissue (AT). Human AT depots vary in their capacity for expansion. Data suggests that subcutaneous (SQ) is adapted for healthy lipid storage. Conversely visceral (V) accumulation is associated with inflammation, obesity-related co-morbidities and Type 2 diabetes (T2DM) risk. We investigated SQ and VAT histologic architecture along with insulin, adipokines and inflammatory markers in relationship to prepregnancy BMI and gestational weight gain (GWG). Methods: Subset of non-diabetic singleton gravidas from the Pregnancy & Postpartum Observational Dietary Study (PPODS), undergoing Cesareans and consenting to SQ & VAT biopsies were included. Average adipocyte size …

Temporal Trends In Serum Concentrations Of Polychlorinated Dioxins, Furans, And Pcbs Among Adult Women Living In Chapaevsk, Russia: A Longitudinal Study From 2000 To 2009, Olivier Humblet, Oleg Sergeyev, Larisa Altshul, Susan A. Korrick, Paige L. Williams, Claude Emond, Linda S. Birnbaum, Jane S. Burns, Mary M. Lee, Boris Revich, Andrey Shelepchikov, Denis Feshin, Russ Hauser

Mary M. Lee

BACKGROUND: The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.

METHODS: Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.

RESULTS: The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the …

Mullerian Inhibiting Substance Recruits Alk3 To Regulate Leydig Cell Differentiation, Xiufeng Wu, Ningning Zhang, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) not only induces Mullerian duct regression during male sexual differentiation but also modulates Leydig cell steroidogenic capacity and differentiation. MIS actions are mediated through a complex of homologous receptors: a type II ligand-binding receptor [MIS type II receptor (MISRII)] and a tissue-specific type I receptor that initiates downstream signaling. The putative MIS type I receptors responsible for Mullerian duct regression are activin A type II receptor, type I [Acvr1/activin receptor-like kinase 2 (ALK2)], ALK3, and ALK6, but the one recruited by MIS in Leydig cells is unknown. To identify whether ALK3 is the specific type I …

Parental Mastery Of Continuous Subcutaneous Insulin Infusion Skills And Glycemic Control In Youth With Type 1 Diabetes, Kathleen Mitchell, Kimberley Johnson, Karen Cullen, Mary M. Lee, Olga T. Hardy

Mary M. Lee

OBJECTIVE: The purpose of this study is to determine whether parental knowledge of the continuous subcutaneous insulin infusion (CSII) device affects glycemic control as measured by hemoglobin A1c (A1C) level. SUBJECTS AND METHODS: Parents of children with type 1 diabetes mellitus (T1DM) using CSII completed a 14-item questionnaire. Questions 1-10 were knowledge-based questions that required the parent to extract specific information from their child's CSII device. Questions 11-14 asked parents to provide a self-assessment of their CSII knowledge. RESULTS: Twenty-two parents of youth with T1DM participated in the study. Ten of the youth were in the Low-A1C group (A1C/=8%). Parents …

Ampk Activation: A Therapeutic Target For Type 2 Diabetes?, Kimberly A. Coughlan, Rudy Valentine, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

Dissecting The Workforce And Workplace For Clinical Endocrinology, And The Work Of Endocrinologists Early In Their Careers, Claude Desjardins, Mark A. Bach, Anne R. Cappola, Ellen W. Seely, Ronald G. Ehrenberg

Ronald G. Ehrenberg

[Excerpt] No national mechanism is in place for an informed, penetrating, and systematic assessment of the physician workforce such as that achieved by the National Science Foundation (NSF) for the periodic evaluation of the nation’s scientists and engineers. Likewise, knowledge of the workforce for clinical research is enigmatic and fragmentary despite the serial recommendations of “blue-ribbon” panels to establish a protocol for the recurrent assessment of clinical investigators early in their careers. Failure to adopt a national system for producing timely, high-quality data on the professional activities of physicians limits the application of improvement tools for advancing clinical investigation and …

Bean And Rice Meals Reduce Postprandial Glycemic Response In Adults With Type 2 Diabetes: A Cross-Over Study, Sharon V. Thompson, Donna M. Winham, Andrea M. Hutchins

Donna Winham

Background: Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods: We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n=3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, …

Perceptions Of Flatulence From Bean Consumption Among Adults In 3 Feeding Studies, Donna M. Winham, Andrea M. Hutchins

Donna Winham

Background: Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods: Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to …

Whole-Body And Muscle Protein Metabolism Are Not Affected By Acute Deviations From Habitual Protein Intake In Older Men: The Hormonal Regulators Of Muscle And Metabolism In Aging (Horma) Study, Kevin E. Yarasheski, Carmen Castaneda-Sceppa, Jiaxiu He, Miwa Kawakubo, Shalender Bhasin, Ellen F. Binder, E. Todd Schroeder, Ronenn Roubenoff, Stan P. Azen, Fred R. Sattler

Carmen Castaneda-Sceppa

Background: Acute deviations in protein intake before the quantification of protein kinetics in older humans may explain the controversy over the effects of older age on muscle protein synthesis and proteolysis rates. Objective: We hypothesized that an acute decrease in protein intake from the habitual intake is associated with lower muscle protein synthesis and higher proteolysis rates, whereas an acute increase in protein intake from the habitual intake is associated with higher muscle protein synthesis and lower proteolysis rates. Design: In 112 community-dwelling healthy men aged 65–90 y, we quantified resting whole-body [1,2-13C2]leucine kinetics, muscle mixed protein fractional synthesis rates …