Medicine and Health Sciences Commons^™

Neuroinflammation And Neurologic Deficits In Diabetes Linked To Brain Accumulation Of Amylin, Sarah Srodulski, Savita Sharma, Adam B. Bachstetter, Jennifer M. Brelsfoard, Conrado Pascual, Xinmin Simon Xie, Kathryn E. Saatman, Linda J. Van Eldik, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized and co-secreted with insulin by pancreatic β-cells. Amylin deposition is promoted by chronic hypersecretion of amylin (hyperamylinemia), which is common in humans with obesity or pre-diabetic insulin resistance. Human amylin oligomerizes quickly when oversecreted, which is toxic, induces inflammation in pancreatic islets and contributes to the development of T2D. Here, we tested the hypothesis that accumulation of oligomerized amylin affects brain function.

METHODS: In contrast to amylin from humans, rodent amylin is neither amyloidogenic nor cytotoxic. …

Cardioprotection By Controlling Hyperamylinemia In A "Humanized" Diabetic Rat Model, Sanda Despa, Savita Sharma, Todd R. Harris, Hua Dong, Ning Li, Nipavan Chiamvimonvat, Heinrich Taegtmeyer, Kenneth B. Margulies, Bruce D. Hammock, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart.

METHODS AND RESULTS: By Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP …

Obesity And Diabetes Cause Cognitive Dysfunction In The Absence Of Accelerated Β-Amyloid Deposition In A Novel Murine Model Of Mixed Or Vascular Dementia, Dana M. Niedowicz, Valerie L. Reeves, Thomas L. Platt, Katharina Kohler, Tina L. Beckett, David K. Powell, Tiffany L. Lee, Travis R. Sexton, Eun Suk Song, Lawrence D. Brewer, Caitlin S. Latimer, Susan D. Kraner, Kara L. Larson, Sabire Özcan, Christopher M. Norris, Louis B. Hersh, Nada M. Porter, Donna M. Wilcock, Michael Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APP^ΔNL/ΔNLx PS1^P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of β-amyloid (Aβ)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small …

Depression And Risk Perceptions In Older African Americans With Diabetes, Barry W. Rovner, Md, Julia A. Haller, Md, Robin J. Casten, Phd, Ann P. Murchison, Md, Mph, Lisa A. Hark, Phd, Rd

Department of Psychiatry and Human Behavior Faculty Papers

Introduction: The purpose of this study is to describe the impact of depression on perceptions of risks to health, diabetes self-management practices, and glycemic control in older African Americans with type 2 diabetes.

Methods: The authors analyzed data on depression, risk perceptions, diabetes self-management, and hemoglobin A1C in African Americans with type 2 diabetes.T tests, chi square, and multivariate regression were used to analyze the data.

Results: The sample included 177 African Americans (68% women) whose average age was 72.8 years. Thirty four (19.2%) participants met criteria for depression. Compared to non-depressed participants, depressed participants scored significantly higher on Personal …

Using Accreditation Standards As A Framework To Evaluate And Improve A Community-Based Diabetes Self-Management Education Program., Neva White, Mary Lou Manning, Rickie Brawer, James Plumb

Department of Nursing papers and presentations

Diabetes self-management education is an essential component of diabetes clinical management, and community-based programs are an effective intervention for improving glycemic control among adults living with diabetes. The National Standards for Diabetes Self-Management Education and Support are designed to define quality diabetes self-management education and support, and to assist diabetes educators to provide evidence-based education and self-management support. These standards are used in the field for recognition and accreditation. This article presents the results of a program evaluation conducted by the Center for Urban Health at the Thomas Jefferson University and Hospital, examines the outcomes of the community-based diabetes self-management …

Meglumine Exerts Protective Effects Against Features Of Metabolic Syndrome And Type Ii Diabetes, Arturo Bravo Nuevo, Alice Marcy, Minzhou Huang, Frank Kappler, Jennifer Mulgrew, Lisa Laury-Kleintop, Melvin Reichman, Annette Tobia, George C Prendergast

PCOM Scholarly Papers

Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine) can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, …