A5077540290- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Metabolism, Diabetes, and Cancer
- Regulation of Appetite and Obesity
- Adipokines, Inflammation, and Metabolic Diseases
- Pancreatic function and diabetes
- Muscle metabolism and nutrition
- Diabetes Treatment and Management
- Lipid metabolism and biosynthesis
- Mitochondrial Function and Pathology
- Pharmacogenetics and Drug Metabolism
- Diabetes and associated disorders
- Click Chemistry and Applications
- Biotin and Related Studies
- Peroxisome Proliferator-Activated Receptors
Yale University
2017-2021
University of New Haven
2018-2019
Scripps Research Institute
2009
Abstract Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of anti-diabetic agents; however, concerns have been raised about their potential to induce euglycemic ketoacidosis and increase both glucose production glucagon secretion. The mechanisms behind these alterations unknown. Here we show that the SGLT2 inhibitor (SGLT2i) dapagliflozin promotes in healthy type diabetic rats setting insulinopenia through increased plasma catecholamine corticosterone concentrations...
Cytochrome P450 (P450) enzymes regulate a variety of endogenous signaling molecules and play central roles in the metabolism xenobiotics drugs. We recently showed that an aryl alkyne serves as effective activity-based probe for profiling mouse liver microsomal P450s vitro vivo. However, individual display distinct substrate inhibitor specificities, indicating multiple structures may be required to achieve comprehensive coverage this large diverse enzyme family. Here, we have synthesized...
Significance Low levels of leptin, a hormone secreted by adipocytes that signals the body as to availability fuel stores, are known increase food intake. Here, we demonstrate mechanism which low leptin stimulates intake in rodents: Under conditions hypoleptinemia, stress (glucocorticoid) production is increased, and turn AgRP neurons promote appetite.
White adipose tissue (WAT) insulin action has critical anabolic function and is dysregulated in overnutrition. However, the mechanism of short-term high-fat diet-induced (HFD-induced) WAT resistance (IR) poorly understood. Based on recent evidences, we hypothesize that a HFD causes IR through plasma membrane (PM) sn-1,2-diacylglycerol (sn-1,2-DAG) accumulation, which promotes protein kinase C-ε (PKCε) activation to impair signaling by phosphorylating receptor (Insr) Thr1160. To test this...
The Metabolic Inflexibility Hypothesis and Randle posit that alterations in muscle glucose fat oxidation are key factors the pathogenesis of obesity (lipid)-associated skeletal insulin resistance. In order to test these hypotheses we used a stable isotope tracer ([U-13C]glucose) measure ratio pyruvate dehydrogenase flux citrate synthase (VPDH/VCS), highly tissue-specific index for proportional contribution total mitochondrial vivo. We found resistant rats fed high diet (HFD) 4 weeks did not...
White adipose tissue (WAT), as an energy storage organ, plays a major role in regulating peripheral insulin resistance and hepatic gluconeogenesis, but the mechanism by which lipid induces WAT is poorly understood. To examine potential of diacylglycerol (DAG) - protein kinase Cε (PKCε) receptor (INSR) pathway mediating lipid-induced resistance, we assessed action liver, muscle 7-day high fat diet (HFD) regular chow (RC) fed rats hyperinsulinemic-euglycemic clamp (HEC) combined with [3-3H]...
Sodium-glucose transport protein 2 inhibitors (SGLT2i) are the most recent class of antidiabetic agents; however concerns have been raised about their potential to induce euglycemic ketoacidosis by an unknown mechanism. Here we report that dapagliflozin increases rates hepatic ketogenesis (35±4 vs. 136±8 μmol/[kg-min], p<0.0001) in normal Sprague-Dawley rats increasing plasma catecholamine (epinephrine 0.5±0.1 7.3±0.5 nM, p<0.001, norepinephrine 2.5±0.5 19.8±5.2 p<0.01)...
Leptin deficiency is known to promote hyperphagia, but the mechanism for this unknown. Here we show that hypoleptinemia-driven hypercorticosteronemia promotes hyperphagia in fasting (40.3±4.9 kcal consumed 2 hour after a 48 fast vs. 2.4±1.0 6 fast, P<0.0001) and poorly-controlled type 1 diabetes (T1D) (28.4±2.5 13.3±2.9 kcal, P<0.01) rats. Correcting hypoleptinemia with leptin infusion reversed reduced food intake control rates both models (48 fast+leptin 5.2±2.2...