A5021219010- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Parkinson's Disease Mechanisms and Treatments
- Diabetes Management and Research
- Genetics, Aging, and Longevity in Model Organisms
- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- Amino Acid Enzymes and Metabolism
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Diet and metabolism studies
- Mitochondrial Function and Pathology
- Insect Resistance and Genetics
- Birth, Development, and Health
- Genetic Neurodegenerative Diseases
- Cerebrovascular and genetic disorders
- Pancreatitis Pathology and Treatment
- Metabolomics and Mass Spectrometry Studies
- Effects and risks of endocrine disrupting chemicals
- Nuclear Receptors and Signaling
- Adenosine and Purinergic Signaling
- Renal Transplantation Outcomes and Treatments
- Stress Responses and Cortisol
Vanderbilt University Medical Center
2012-2024
Vanderbilt University
2015-2024
Nashville Oncology Associates
2019-2024
Diabetes Australia
2017-2020
College of the Atlantic
2018
Emory University
2008-2012
University of Tennessee at Knoxville
2006
Exposure to pesticides has been suggested increase the risk of Parkinson's disease (PD), but mechanisms responsible for this association are not clear. Here, we report that perinatal exposure mice during gestation and lactation low levels dieldrin (0.3, 1, or 3 mg/kg every days) alters dopaminergic neurochemistry in their offspring exacerbates MPTP toxicity. At 12 wk age, protein mRNA dopamine transporter (DAT) vesicular monoamine 2 (VMAT2) were increased by a dose-related manner. We then...
Glucagon is a critical regulator of glucose homeostasis; however, mechanisms regulating glucagon action and α-cell function number are incompletely understood. To elucidate the role hepatic receptor (Gcgr) in action, we generated mice with hepatocyte-specific deletion receptor. Gcgr(Hep)(-/-) exhibited reductions fasting blood improvements insulin sensitivity tolerance compared wild-type controls, similar magnitude to changes observed Gcgr(-/-) mice. Despite preservation islet Gcgr...
Posttransplantation diabetes mellitus (PTDM) is a common and significant complication related to immunosuppressive agents required prevent organ or cell transplant rejection. To elucidate the effects of 2 commonly used agents, calcineurin inhibitor tacrolimus (TAC) mTOR sirolimus (SIR), on islet function test whether these could be reversed prevented, we investigated human islets transplanted into immunodeficient mice treated with TAC SIR at clinically relevant levels. Both impaired insulin...
Abstract Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content abundance. The physiological function bioenergetic capacity of mitochondria connected the structure, folding, organization inner‐membrane cristae. During aging process, mitochondrial dysfunction is observed, regulatory balance dynamics often disrupted, leading increased fragmentation in cells. Therefore, it hypothesized that significant...
Glucagon plays a major role in the regulation of glucose homeostasis during fed and fasting states. However, mechanisms responsible for pancreatic α cell mass function are not completely understood. In current study, we identified mTOR complex 1 (mTORC1) as regulator glucagon secretion. Using mice with tissue-specific deletion mTORC1 Raptor cells (αRaptorKO), showed that signaling is dispensable development, but essential maturation transition from milk-based diet to chow-based after...
Significance Both type 1 and 2 diabetes are associated with reduced β-cell mass or function, resulting from decreased proliferation increased apoptosis. Understanding the signals governing survival regeneration is critical for developing strategies to maintain healthy populations of these cells in individuals. forms hyperglucagonemia an plasma glucagon:insulin ratio. Glucagon excess contributes metabolic dysregulation diabetic state glucagon receptor antagonism a potential target area...
Abstract Glucagon has emerged as a key regulator of extracellular amino acid (AA) homeostasis. Insufficient glucagon signaling results in hyperaminoacidemia, which drives adaptive proliferation glucagon-producing α cells. Aside from mammalian target rapamycin complex 1 (mTORC1), the role other AA sensors cell not been described. Here, using both genders mouse islets and receptor ( gcgr )-deficient zebrafish Danio rerio ), we show requires activation signal-regulated protein kinase (ERK1/2)...
Glucagon antagonism is a potential treatment for diabetes. One side effect α-cell hyperplasia, which has been noted in several approaches to antagonize glucagon action. To investigate the molecular mechanism of hyperplasia and identify responsible factor, we created zebrafish model receptor (gcgr) signaling interrupted. The genetically chemically tractable zebrafish, provides robust discovery platform, two gcgr genes ( gcgra gcgrb ) its genome. Sequence, phylogenetic, synteny analyses...
Abstract Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that increases expression genes for cell identity, protein processing, organelle Gene regulatory network analysis reveal activates transcription factors important identity homeostasis, while imaging metabolomics demonstrates upon are more energetically...
Since the discovery of glucagon 100 years ago, hormone and pancreatic islet alpha cells that produce it have remained enigmatic relative to insulin-producing beta cells. Canonically, been described in context glucagon’s role glucose metabolism liver, with as primary nutrient signal regulating cell function. However, current data reveal a more holistic model metabolic signalling, involving glucagon-regulated multiple nutrients by liver other tissues, including amino acids lipids, providing...
Interrupting glucagon signaling decreases gluconeogenesis and the fractional extraction of amino acids by liver from blood resulting in lower glycemia. The hyperaminoacidemia stimulates α cell proliferation secretion via a liver-α axis. We hypothesized that cells detect respond to circulating levels unique acid transporter repertoire. found
Recent clinical evidence supports a link between 25-hydroxyvitamin D insufficiency (serum [25(OH)D] levels <30 ng/mL) and Parkinson’s disease. To investigate the effect of 25(OH)D depletion on neuronal susceptibility to toxic insult, we induced state deficiency in mice then challenged them with dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found there was no significant difference control 25(OH)D-deficient animals striatal dopamine or transporter tyrosine...
Abstract Selective inhibitors of sodium glucose cotransporter-2 (SGLT2) are widely used for the treatment type 2 diabetes and act primarily to lower blood by preventing reabsorption in kidney. However, it is controversial whether these agents also on pancreatic islet, specifically α cell, increase glucagon secretion. To determine effects SGLT2 human islets, we analyzed expression hormone secretion islets treated with inhibitor dapagliflozin (DAPA) vitro vivo. Compared kidney, SLC5A2...
Dysregulated glucagon secretion and inadequate functional beta cell mass are hallmark features of diabetes. While receptor (GCGR) antagonism ameliorates hyperglycemia elicits regeneration in pre-clinical models diabetes, it also promotes alpha delta hyperplasia. We sought to investigate the mechanism by which loss action impacts pancreatic islet non-alpha cells, relevance these observations a human context.
Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content abundance. The physiological function bioenergetic capacity of mitochondria connected the structure, folding, organization inner-membrane cristae. During aging process, mitochondrial dysfunction is observed, regulatory balance dynamics often disrupted, leading increased fragmentation in cells. Therefore, we hypothesized that significant...
Summary Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure function of pancreatic beta cells over the lifetime animal remains unknown. Here, we used single nucleus transcriptomics to show that increases expression genes for cell identity, protein processing, organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype transcription factors involved in identity...