Medicine and Health Sciences Commons^™

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …

The Glycemic, Cholesterol, And Weight Effects Of L-Carnitine In Diabetes: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Jennifer Ko, Eva Y. Wong, Huyentran N. Tran, Rebecca J.C. Tran, Diana X. Cao

Pharmacy Faculty Articles and Research

Introduction

L-carnitine possibly impacts insulin sensitivity and glucose metabolism. However, its therapeutic role in diabetes is poorly understood.

Methods

A systematic review and meta-analysis were conducted using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception through June 30, 2021. Included studies evaluated the use of L-carnitine in diabetes on fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), weight, or body mass index (BMI). Weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random-effects model.

Results

Seventeen studies …

Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen

Chemistry Faculty Publications

Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2- AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or basecatalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate …

Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying

Honors Thesis

The Zn(II) metal ion has been shown to interact with Islet Amyloid Polypeptide (IAPP), a protein implicated in the progression of Type II Diabetes Mellitus, in such a way as to prevent the protein from aggregating into toxic fibers. We set out to find whether other metal ions might similarly prevent IAPP aggregation. Using Thioflavin T (ThT) spectroscopic assays, which measure fluorescence of ThT upon binding to aggregated IAPP, we observed a decrease in aggregation when incubated with Zn(II), Cu(II), Ni(II), and Sn(II). Atomic Force Microscopy (AFM), which can visualize fibril formation, revealed that the metals were not inhibiting IAPP …

Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton

Honors Capstone Projects - All

Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.^1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point of interest in studying GOAT whereby blocking the acylation of the ghrelin could potentially halt the activity of the peptide hormone and provide a means of treating obesity, diabetes, and other diseases affected by ghrelin levels. The duration of my project involved working …

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. …

Regulation Of Ghrelin: A Possible Treatment Option For Obesity And Diabetes, Sarah Picciotto

The Science Journal of the Lander College of Arts and Sciences

Obesity is a mounting problem in America today. One major concern about obesity is that it is a risk factor for type 2 diabetes, a disease that impairs insulin sensitivity and secretion. This interferes with blood glucose levels and can cause hyperglycemia, which is when there is too much circulating glucose in the blood. Ghrelin, an amino acid peptide responsible for appetite stimulation and energy balance, plays a direct role in insulin secretion and glucose metabolism. In many experiments, elevated ghrelin levels are associated with decreased insulin secretion from pancreatic islet cells. Although ghrelin concentration is decreased in obese individuals …

Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang

Department of Cancer Biology Faculty Papers

Altered lipid metabolism underlies several major human diseases, including obesity and type 2 diabetes. However, lipid metabolism pathophysiology remains poorly understood at the molecular level. Insulin is the primary stimulator of hepatic lipogenesis through activation of the SREBP-1c transcription factor. Here we identified cyclin-dependent kinase 8 (CDK8) and its regulatory partner cyclin C (CycC) as negative regulators of the lipogenic pathway in Drosophila, mammalian hepatocytes, and mouse liver. The inhibitory effect of CDK8 and CycC on de novo lipogenesis was mediated through CDK8 phosphorylation of nuclear SREBP-1c at a conserved threonine residue. Phosphorylation by CDK8 enhanced SREBP-1c ubiquitination and protein …

Impaired M3 And Enhanced M2 Muscarinic Receptor Contractile Function In A Streptozotocin Model Of Mouse Diabetic Urinary Bladder, K. J. Pak, Rennolds S. Ostrom, M. Matsui, F. J. Ehlert

Pharmacy Faculty Articles and Research

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg−1) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after …