A5029283963- Hormonal Regulation and Hypertension
- Pancreatic function and diabetes
- Ion Transport and Channel Regulation
- Estrogen and related hormone effects
- Sphingolipid Metabolism and Signaling
- Diet, Metabolism, and Disease
- Diabetes Treatment and Management
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and disorders
- Pharmacogenetics and Drug Metabolism
- SARS-CoV-2 and COVID-19 Research
- Receptor Mechanisms and Signaling
- Paraoxonase enzyme and polymorphisms
- Pharmacological Effects of Natural Compounds
- Metabolism, Diabetes, and Cancer
- CRISPR and Genetic Engineering
- Vitamin C and Antioxidants Research
- Diabetes and associated disorders
- Liver Disease Diagnosis and Treatment
- Adipose Tissue and Metabolism
University of California, Berkeley
2019-2023
University of California, San Francisco
2023
Berkeley College
2019
Abstract The classical dogma of glucocorticoid-induced insulin resistance is that it caused by the transcriptional activation hepatic gluconeogenic and genes glucocorticoid receptor (GR). Here, we find glucocorticoids also stimulate expression insulin-sensitizing genes, such as Irs2 . coregulator EHMT2 can serve a coactivator or corepressor. Using male mice have defective coactivation function specifically, show transcription dependent on liver EHMT2’s IRS2 play key role in mediating...
Chronic or excess glucocorticoid exposure causes lipid disorders such as hypertriglyceridemia and hepatic steatosis. Angptl4 (angiopoietin-like 4), a primary target gene of the receptor in hepatocytes adipocytes, is required for steatosis induced by synthetic dexamethasone. has also been shown to be dexamethasone-induced ceramide production. Here, we further examined role ceramide-mediated signaling dyslipidemia caused chronic exposure. Using stable isotope-labeling technique, found that...
Abstract Gpr27 is a highly conserved, orphan G protein coupled receptor (GPCR) previously implicated in pancreatic beta cell insulin transcription and glucose-stimulated secretion vitro . Here, we characterize whole-body mouse knockout of mice were born at expected Mendelian ratios exhibited no gross abnormalities. Insulin Pdx1 mRNA islets reduced by 30%, but this did not translate to reduction islet content or mass. slightly worsened glucose tolerance with lower plasma levels while...
Understanding the interactions between SARS-CoV-2 and host cell machinery may reveal new targets to treat COVID-19. We focused on an interaction ORF3A accessory protein CLIC-like chloride channel-1 (CLCC1). found that partially co-localized with CLCC1 could be co-immunoprecipitated. Since plays a role in unfolded response (UPR), we hypothesized also play UPR. Indeed, expression triggered transcriptional UPR was similar knockdown of . 293T cells induced death this rescued by chemical...
It is well established that chronic glucocorticoid exposure causes hyperglycemia. While receptor (GR) stimulates hepatic gluconeogenic gene transcription, additional mechanisms are activated by to enhance gluconeogenesis. We found treatment sphingosine-1-phosphate (S1P)–mediated signaling. Hepatic knockdown of S1P 1 (S1PR1) had no effect on glucocorticoid-induced glucose intolerance but elevated fasting plasma insulin levels. In contrast, S1PR3 exacerbated without affecting Finally, S1PR2...
Abstract Islet transplantation can cure type 1 diabetes, but peri-transplant beta cell death limits this procedure to those with low insulin requirements. Improving human survival or proliferation may make islet a possibility for more patients. To identify novel regulators of and proliferation, we conducted pooled small hairpin RNA (shRNA) screen in primary cells transplanted into immunocompromised mice. shRNAs targeting several cyclin dependent kinase inhibitors were enriched after...
Chloride is one of the most abundant electrolytes and has many important physiological functions. Though it known that chloride plays a role in beta cell physiology insulin secretion, intracellular fluxes how they affect development function are relatively poorly understood. Clic-like channel 1 (Clcc1) an endoplasmic reticulum (ER) localized whose loss causes ER stress death neurons retinal cells. We found Clcc1 specific knockout (Clcc1 beta-KO) mice were glucose intolerant with lower plasma...
Virus-mediated gene knockdown in intact pancreatic islets is technically challenging due to poor infection of the center islet. Because cells that do not have normal insulin secretion, measuring changes secretion after challenging. We describe a method monitor from only beta with interest using single lentivirus containing guide RNA, luciferase reporter and dCas9-KRAB cassette. This allows rapid inexpensive monitoring those knockdown, circumventing problem incomplete islet infection.
<p>It is well-established that chronic glucocorticoid exposure causes hyperglycemia. While receptor (GR) stimulates hepatic gluconeogenic gene transcription, additional mechanisms are activated by to enhance gluconeogenesis. We found treatment sphingosine-1-phosphate (S1P)-mediated signaling. Hepatic knockdown of S1P 1 (S1PR1) had no effect on glucocorticoid-induced glucose intolerance but elevated fasting plasma insulin levels. In contrast, S1PR3 exacerbated without affecting Finally,...
<p>It is well-established that chronic glucocorticoid exposure causes hyperglycemia. While receptor (GR) stimulates hepatic gluconeogenic gene transcription, additional mechanisms are activated by to enhance gluconeogenesis. We found treatment sphingosine-1-phosphate (S1P)-mediated signaling. Hepatic knockdown of S1P 1 (S1PR1) had no effect on glucocorticoid-induced glucose intolerance but elevated fasting plasma insulin levels. In contrast, S1PR3 exacerbated without affecting Finally,...
Abstract Disclosure: R.A. Lee: None. M. Chang: A. Tsay: Y. D. Li: N. Yiv: S. Tian: J. Wang: Glucocorticoids are steroid hormones whose circulating levels elevated in response to stress maintain metabolic homeostasis. also used treat inflammatory and autoimmune diseases due their potent anti-inflammatory immunomodulatory activities. However, chronic glucocorticoid treatment causes various disorders, such as hyperglycemia insulin resistance. convey functions through an intracellular receptor...
It is well established that chronic and/or excess glucocorticoid (GC) exposure causes glucose and lipid homeostasis disorders. Previous studies have shown elevates hepatic ceramide production to inhibit insulin action increase triglyceride accumulation in the liver. Glucocorticoid treatment not only increases levels of ceramides, but also sphingosine-1-phosphate (S1P). This because glucocorticoids promote synthetic pathway, expression sphingosine kinase 1 (Sphk1). Ceramides can be converted...