A5031811169- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Diabetes and associated disorders
- Muscle metabolism and nutrition
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Pancreatitis Pathology and Treatment
- Diabetes Treatment and Management
- Peroxisome Proliferator-Activated Receptors
- Cardiovascular and exercise physiology
- Diabetes Management and Research
- Cardiovascular Function and Risk Factors
- Diet and metabolism studies
- Opioid Use Disorder Treatment
- Immune cells in cancer
- Veterinary Pharmacology and Anesthesia
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- Parkinson's Disease Mechanisms and Treatments
- Hemodynamic Monitoring and Therapy
- Immunodeficiency and Autoimmune Disorders
- Epigenetics and DNA Methylation
City of Hope
2017-2025
Beckman Research Institute
2017-2025
City Of Hope National Medical Center
2020-2025
Indiana University – Purdue University Indianapolis
2010-2023
Indiana University School of Medicine
2010-2023
Indianapolis Zoo
2013-2018
Indiana University
2011-2016
University School
2013-2014
Center for Children
2013
Vanderbilt University
2002-2010
Obesity has reached epidemic proportions worldwide and reports estimate that American children consume up to 25% of calories from snacks. Several animal models obesity exist, but studies are lacking compare high-fat diets (HFD) traditionally used in rodent diet-induced (DIO) consisting food regularly consumed by humans, including high-salt, high-fat, low-fiber, energy dense foods such as cookies, chips, processed meats. To investigate the obesogenic inflammatory consequences a cafeteria diet...
To characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains.Hyperinsulinemic-euglycemic (approximately 8.5 mmol/l) and -hypoglycemic 3.0 clamps were done catheterized, 5-h-fasted mice to assess insulin action hypoglycemic counter-regulatory responsiveness. Hyperglycemic 15 secretion compared with results perifused islets.Insulin secretory phenotypes varied considerably four strains. In vivo was greatest 129X1/Sv mice, but the response hypoglycemia...
Stimulation of nitric oxide-cGMP signaling results in vascular relaxation and increased muscle glucose uptake. We show that chronically inhibiting cGMP hydrolysis with the phosphodiesterase-5 inhibitor sildenafil improves energy balance enhances vivo insulin action a mouse model diet-induced resistance. High-fat-fed mice treated plus L-arginine or alone for 12 weeks had reduced weight fat mass due to expenditure. However, uncoupling protein-1 levels were not sildenafil-treated mice. Chronic...
Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal comprises the vast majority of insulin-sensitive tissue and is a site dysregulation insulin-resistant state. The biochemical histological composition well defined variety species. However, functional consequences adaptations physiological pathophysiological conditions are not understood. regulation complex. Sites involved by three-step process consisting of: (1) delivery muscle, (2)...
Type 2 diabetes is characterized by a defect in insulin action. The hyperinsulinemic-euglycemic clamp, or widely considered the "gold standard" method for assessing action vivo. During an hyperinsulinemia achieved constant infusion. Euglycemia maintained via concomitant glucose infusion at variable rate. This rate (GIR) determined measuring blood brief intervals throughout experiment and adjusting GIR accordingly. indicative of whole-body action, as mice with enhanced require greater GIR....
A novel approach to regulate obesity-associated adipose inflammation may be through metabolic reprogramming of macrophages (MΦs). Broadly speaking, MΦs dependent on glucose are pro-inflammatory, classically activated (CAM), which contribute and insulin resistance. In contrast, that primarily metabolize fatty acids alternatively (AAM) maintain tissue sensitivity. actuality, there is much flexibility overlap in the CAM-AAM spectrum vivo upon various stimuli microenvironment. We hypothesized...
The maintenance of intracellular Ca(2+) homeostasis in the pancreatic β-cell is closely regulated by activity sarco-endoplasmic reticulum ATPase (SERCA) pump. Our data demonstrate a loss SERCA2b expression several models type 2 diabetes including islets from db/db mice and cadaveric diabetic human islets. Treatment 832/13 rat INS-1-derived cells with 25 mm glucose proinflammatory cytokine IL-1β led to similar expression, which was prevented treatment peroxisome proliferator-activated...
Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) fat undergo extensive adipogenesis during age. Thus, despite the low turnover rate of adipocytes young adults, is unlocked Transplantations quantitatively showed APCs middle-aged exhibited high adipogenic capacity cell-autonomously. Single-cell RNA sequencing identified a distinct APC population, committed...
The homeodomain transcription factor Nkx6.1 plays an important role in pancreatic islet β-cell development, but its effects on adult function, survival, and proliferation are not well understood. In the present study, we demonstrated that treatment of primary rat islets with a cytomegalovirus promoter-driven recombinant adenovirus containing cDNA (AdCMV-Nkx6.1) causes dramatic increases [methyl-3H] thymidine 5-bromo-2′-deoxyuridine (BrdU) incorporation number cells per relative to treated...
Metabolic disorders such as obesity and diabetes mellitus can cause dysfunction of endothelial cells (ECs) vascular rarefaction in adipose tissues. However, the modulatory role ECs tissue function is not fully understood. Other than growth factor-vascular factor receptor-mediated angiogenic signaling, little known about EC-derived signals regulation. We previously identified Argonaute 1 (AGO1; a key component microRNA-induced silencing complex) crucial regulator hypoxia-induced angiogenesis....
Abstract Diabetic kidney disease (DKD) is a major complication of diabetes. Expression members the microRNA (miRNA) miR-379 cluster increased in DKD. miR-379, most upstream 5′-miRNA cluster, functions endoplasmic reticulum (ER) stress by targeting EDEM3. However, vivo remain unclear. We created knockout (KO) mice using CRISPR-Cas9 nickase and dual guide RNA technique characterized their phenotype screened for targets renal mesangial cells from WT vs. miR-379KO AGO2-immunopreciptation CLASH...
Type 1 diabetes results from islet β-cell death and dysfunction induced by an autoimmune mechanism. Proinflammatory cytokines such as interleukin-1β γ-interferon are mediators of this cytotoxicity, but the mechanism which damage occurs is not well understood. In current study, we present multiple lines evidence supporting conclusion that cytokine-induced killing rat β-cells predominantly a nonapoptotic mechanism, including following: 1) A line selected for resistance to cytotoxicity (833/15)...
Type 2 diabetes is characterized by a defect in insulin action. The hyperinsulinemic-euglycemic clamp, or widely considered the "gold standard" method for assessing action vivo. During an hyperinsulinemia achieved constant infusion. Euglycemia maintained via concomitant glucose infusion at variable rate. This rate (GIR) determined measuring blood brief intervals throughout experiment and adjusting GIR accordingly. indicative of whole-body action, as mice with enhanced require greater GIR....
Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during exercise because overexpression does not increase exercise-stimulated MGU. Instead of transport, phosphorylation a primary limitation It was hypothesized partial ablation would impair MGU when capacity but do so increased. Thus, C57BL/6J mice with hexokinase II (HKII) (HK(Tg)), knock-out (G4(+/-)), or both (HK(Tg) + G4(+/-)) and wild-type (WT) littermates were implanted carotid...
Muscle glucose uptake (MGU) is distributively controlled by three serial steps: delivery of to the muscle membrane, transport across and intracellular phosphorylation 6-phosphate hexokinase (HK). During states high fluxes such as moderate exercise, HK activity increased importance, since augmented perfusion increases delivery, GLUT4 at cell membrane transport. Because II overexpression augments exercise-stimulated MGU, it was hypothesized that a reduction in would impair MGU magnitude this...
The aim of the present study was to determine specific sites impairment muscle glucose uptake (MGU) in insulin-resistant high-fat-fed, conscious C57BL/6J mouse. Wild type (WT) and hexokinase II overexpressing (HKTg) mice were fed either a standard diet or high-fat studied at 4 months age. A carotid artery jugular veins had catheters chronically implanted for sampling infusions, respectively, allowed recovery least 5 days. Mice fasted h underwent hyperinsulinemic-euglycemic clamp saline...
The aim of this study was to test whether in fact glucose transport is rate-limiting control muscle uptake (MGU) under physiological hyperinsulinaemic conditions the conscious, unrestrained mouse. C57Bl/6J mice overexpressing GLUT4 (GLUT4(Tg)), hexokinase II (HK(Tg)), or both (GLUT4(Tg) + HK(Tg)), were compared wild-type (WT) littermates. Catheters implanted into a carotid artery and jugular vein for sampling infusions at 4 month age. After 5-day recovery period, conscious underwent one two...
Muscle glucose uptake (MGU) is determined by delivery, transport, and phosphorylation. C57Bl/6J mice overexpressing GLUT4, hexokinase II (HK II), or both were used to determine the barriers MGU. A carotid artery jugular vein catheterized for arterial blood sampling venous infusions. Experiments conducted in conscious ∼7 days after surgery. 2-Deoxy-[ 3 H]glucose was administered during rest treadmill exercise calculate concentration-dependent (R g ) -independent (K indexes of Compared with...
The absence of GLUT4 severely impairs basal glucose uptake in vivo , but does not alter homeostasis or circulating insulin. Glucose isolated contracting skeletal muscle (MGU) is also impaired by the GLUT4, and onset fatigue hastened. Whether body can compensate preserve during exercise, as it state, unknown. One aim was to test effectiveness glucoregulatory compensation for vivo. used further define role hexokinase (HK) II, which catalyses phosphorylation after transported cell. HK II...
Abstract Glucocorticoids can cause steroid-induced diabetes or accelerate the progression to by creating systemic insulin resistance and decreasing functional β-cell mass, which is influenced changes in function, growth, death. The synthetic glucocorticoid agonist dexamethasone (Dex) deleterious mass survival, proliferation. However, mechanism Dex decreases proliferation unknown. Interestingly, induces transcription of an antiproliferative factor negative regulator epidermal growth receptor...
Abstract Mitochondrial dysfunction is implicated in skeletal muscle insulin resistance. Syntaxin 4 (STX4) levels are reduced human diabetic muscle, and global transgenic enrichment of STX4 expression improves sensitivity mice. Here, we show that muscle-specific (skmSTX4tg) mice reverses established resistance mitochondrial function the context diabetogenic stress. Specifically, skmSTX4tg reversed caused by high-fat diet (HFD) without altering body weight or food consumption. Electron...
Pancreatic islets are three-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing establish aggregation. By combining genetic animal models, imaging tools, gene expression profiling, we demonstrate that regulated by extracellular matrix signaling cell-cell adhesion. Islet cell-specific inactivation receptor...
Abstract Objective To determine the pharmacokinetics of extended-release buprenorphine (XRB) in adult swine. We hypothesized that after a single SC administration XRB swine, plasma concentrations would be at or above therapeutic threshold 0.1 ng/mL and not result major injection site reactions. Methods Extended-release was administered once to 2 cohorts female Yorkshire swine low (0.2 mg/kg) high doses (0.4 mg/kg). Blood collected from an indwelling jugular catheter prior for 13 total time...
Hexokinase (HK) II content is elevated in fatigue resistant muscle fibres and exercise trained muscle. The aim of this study was to determine if capacity dependent on HK protein content. C57Bl/6 mice with a 50% knockout (HK +/− ), no genetic manipulation (wild‐type, WT) an ∼3‐fold overexpression Tg ) were tested. Mice ( n = 12/group) completed both maximal oxygen consumption test endurance (run at ∼75% enclosed treadmill equipped measure gas exchange. Arterial venous catheters surgically...
Relatively little is known about the in vivo functions of alpha subunit heterotrimeric G protein Gz (Galphaz). Clues to one potential function recently emerged with finding that activation Galphaz inhibits glucose-stimulated insulin secretion an insulinoma cell line (Kimple, M. E., Nixon, A. B., Kelly, P., Bailey, C. L., Young, K. H., Fields, T. A., and Casey, P. J. (2005) Biol. Chem. 280, 31708-31713). To extend this study vivo, a knock-out mouse model was utilized determine whether plays...