A5017612458- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Diabetes Management and Research
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Diabetes and associated disorders
- Cannabis and Cannabinoid Research
- Endoplasmic Reticulum Stress and Disease
- Protein Degradation and Inhibitors
- Nutritional Studies and Diet
- Diabetes Treatment and Management
- Autophagy in Disease and Therapy
- Pancreatitis Pathology and Treatment
- Regulation of Appetite and Obesity
- Peroxisome Proliferator-Activated Receptors
- Calcium signaling and nucleotide metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Neuroscience and Neuropharmacology Research
- Lipid metabolism and biosynthesis
- Adenosine and Purinergic Signaling
- Thermoregulation and physiological responses
- Ion channel regulation and function
Boston University
2016-2025
University School
2020-2023
Cardiovascular Research Center
2016
Boston Medical Center
1996-2013
University Medical Center
1996-2013
Karolinska Institutet
1994-2007
Hebrew University of Jerusalem
2007
Hadassah Medical Center
2007
University of Iowa
2001
Children's Hospital of Philadelphia
2001
One of the unique features beta-cells is their relatively low expression many antioxidant enzymes. This could render susceptible to oxidative damage but may also provide a system that sensitive reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation H2O2. both models, insulin secretion be stimulated by provision either exogenous H2O2 or diethyl maleate, which raises levels. Provision scavengers, including cell...
hypothesis proposing a role for acyl-CoA esters in nutrient-induced insulin release (Prentki, M., and Matschinsky,
To gain insight into the relationship between acyl coenzyme A (CoAf esters and glucose-induced insulin release, acyl-CoA profiles were determined in clonal pancreatic @-cells (HIT).A high sensitivity per- formance liquid chromatography method was used to measure malonyl, succinyl, &hydroxy 8-methylglutaryl acetyl-CoA free CoASH.Malonyl-CoA content increased more than %fold following exposure of HIT cells 10 m M glucose.The rise malonyl-CoA, which preceded secretion, evident 2 min after...
Insulin secretion in the intact organism, and by perfused pancreas groups of isolated perifused islets, is pulsatile. We have proposed a metabolic model glucose-induced insulin which oscillations ATP/ADP ratio drive alterations electrical events that lead to release. A key prediction our metabolically driven Ca2+ will also occur. Using fluorescent probe, fura 2, digital image analysis, sensitive O2 electrodes, we investigated cytosolic free responses consumption rat islets had been...
Several proteins that are of importance for membrane trafficking in the nerve terminal have recently been characterized. We used Western blot and immunohistochemistry to show synaptotagmin, synaptobrevin/VAMP (vesicle-associated protein), SNAP-25 (synaptosomal-associated protein 25 kDa), syntaxin present cells islets Langerhans endocrine pancreas. Synaptotagmin-like immunoreactivity (-LI) was localized granules within cytoplasm a few located periphery islets, identified as...
Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic β cells. The molecular mechanisms involved are not fully understood but believed to involve inhibition potassium channels sensitive adenosine triphosphate (K ATP channels) in the cell membrane, causing membrane depolarization, calcium influx, and activation secretory machinery. In addition these effects, also promoted exocytosis by direct interaction with...
Highlights•TMLHE controls the neural stem cell (NSC) pool in embryonic mouse neocortex•CPT1A and fatty acid mobilization from lipid droplets regulate NSC pool•TMLHE deficiencies lead to increased symmetric differentiating division of NSCs•NSC defects under TMLHE can be rescued by exogenous carnitineSummaryInborn errors metabolism (IEMs) occur with high incidence human populations. Especially prevalent among these are inborn β-oxidation (FAO), which clinically associated developmental...
Non-insulin-dependent diabetes mellitus is associated with, in addition to impaired insulin release, elevated levels of free fatty acids (FFA) the blood. Insulin release stimulated when beta-cells are acutely exposed FFA, whereas chronic exposure may inhibit glucose-induced secretion. In present study we investigated direct effects long chain acyl-CoA (LC-CoA), active intracellular form on exocytosis. Palmitoyl-CoA both from streptolysin-O-permeabilized HIT cells and fusion secretory...
Neomycin, an antibiotic previously thought to interact specifically with inositol‐containing phospholipids, was found inhibit IP 3 ‐mediated Ca 2+ release from the intracellular stores of permeabilized insulinoma and liver cells. This inhibition could be relieved by increasing concentration. Radiolabelled bind tightly columns prepared neomycin covalently attached glass beads. ATP also bound these colums. It is concluded that acts in biological systems as a weak anion exchanger therefore...
Displacement of Bromodomain and Extra-Terminal (BET) proteins from chromatin has promise for cancer inflammatory disease treatments, but roles BET in metabolic remain unexplored. Small molecule inhibitors, such as JQ1, block protein binding to acetylated lysines, lack selectivity within the family (Brd2, Brd3, Brd4, Brdt), making it difficult disentangle contributions each member transcriptional cellular outcomes. Here, we demonstrate multiple improvements pancreatic β-cells upon inhibition...
We show in the accompanying paper that steadystate level of free Ca2+ maintained by organelles permeabilized RINm5F insulinoma cells varies inversely with ATP/ADP ratio when this is set addition creatine phosphokinase and fixed ratios to phosphate.We, therefore, asked whether acute cyclic alterations cytosolic ATP/ ADP range known modulate O2 consumption might be involved regulating physiological activity Ca2+-ATPases level.To explore hypothesis we combined two experimental systems: 1) can...
It is a desirable goal to stimulate fuel oxidation in adipocytes and shift the balance toward less storage more burning. To understand this regulatory process, respiration was measured primary rat adipocytes, mitochondria, fat-fed mice. Maximum O(2) consumption, vitro, determined with chemical uncoupler of oxidative phosphorylation (carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)). The adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio by luminescence. Mitochondria were...
Chronic exposure (24–72 hrs) of pancreatic islets to elevated glucose and fatty acid leads glucolipoxicity characterized by basal insulin hypersecretion impaired glucose-stimulated secretion (GSIS). Our aim was determine the mechanism for insulin. We used mono-oleoyl-glycerol (MOG) as a tool rapidly increase lipids in isolated rat ß-cells clonal ß-cell line INS-1 832/13. MOG (25–400 µM) stimulated from concentration dependent manner without increasing intracellular Ca2+ or O2 consumption....
Cytosolic free Ca2+ rises in pancreatic @-cells response to glucose stimulation and is part of the coupling insulin secretion.This study evaluates a possible role for cytosolic long chain acyl-CoA esters modulating handling by clonal j3-cells (HIT).Intact cells incubated with 20 PM palmitic acid exhibited 40% decrease basal Ca2+.In contrast, esters, up length 16, but not corresponding fatty acids, significantly lowered set point maintained permeabilized saponin.The maximum various increased...
To gain insight into the regulation of pancreatic beta-cell mitochondrial metabolism, direct effects on respiration different substrates, variations in ATP/ADP ratio and free Ca2+ were examined using isolated mitochondria permeabilized clonal beta-cells (HIT). Respiration from pyruvate was high not influenced by State 3 or under various redox states fixed values ratio; nevertheless, elevated pyridine nucleotide fluorescence, indicating activation dehydrogenase Ca2+. Furthermore, presence...