Glucose regulates expression of inositol 1,4,5-trisphosphate receptor isoforms in isolated rat pancreatic islets. 1999

B Lee, and J C Jonas, and G C Weir, and S G Laychock
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, the State University of New York at Buffalo, 14214, USA.

Isolated rat pancreatic islets were studied to determine the dynamic regulatory effects of glucose stimulation on the expression of messenger RNA (mRNA) and protein levels for inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) isoforms I, II, and III. The relative isoform abundance was: IP3R-III > IP3R-II approximately IP3R-I. Culture of islets with glucose (G; 20 mM) or alpha-ketoisocaproic acid for 30 min increased only IP3R-III mRNA expression above control (5.5 mM glucose). 2-Deoxyglucose was without effect. Islet culture for 2 h with G (20 mM) or alpha-ketoisocaproic acid reduced IP3R-III mRNA expression levels below control, and cycloheximide blocked the response. Culturing islets for 1 day or 7 days with G (11 mM) reduced the expression of IP3R-III mRNA but increased the expression of IP3R-II mRNA in a time-dependent manner. Cytosine arabinoside lowered cultured islet IP3R-II and -III mRNA levels, but glucose effects remained evident. IP3R-II mRNA levels were also significantly higher in islets from hyperglycemic 90% partial pancreatectomized rats, compared with sham animals. Islet IP3R mRNA expression also showed osmotic sensitivity. Islet IP3R-III protein levels increased after 2 h islet culture at 20 mM G, were unchanged after 1 day culture at 11 mM G, and were lower than control after 7 days culture at 11 mM G. In contrast, IP3R-II levels increased after 1 day and 7 days culture at 11 mM G, whereas IP3R-I protein levels remained unchanged. Thus, G stimulation rapidly increases transcription and expression of IP3R-III mRNA and protein levels in rat islets. However, chronic G stimulation up-regulates IP3R-II mRNA in cultured islets and in islets from partial pancreatectomized rats. Metabolic regulation of IP3R-II and III expression may mediate beta-cell IP3-responsive Ca2+ mobilization and insulin secretion.

UI MeSH Term Description Entries
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D007651 Keto Acids Carboxylic acids that contain a KETONE group. Oxo Acids,Oxoacids,Acids, Keto,Acids, Oxo
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D009994 Osmolar Concentration The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Ionic Strength,Osmolality,Osmolarity,Concentration, Osmolar,Concentrations, Osmolar,Ionic Strengths,Osmolalities,Osmolar Concentrations,Osmolarities,Strength, Ionic,Strengths, Ionic
D010180 Pancreatectomy Surgical removal of the pancreas. (Dorland, 28th ed) Pancreatectomies
D011500 Protein Synthesis Inhibitors Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins. Protein Synthesis Antagonist,Protein Synthesis Antagonists,Protein Synthesis Inhibitor,Antagonist, Protein Synthesis,Antagonists, Protein Synthesis,Inhibitor, Protein Synthesis,Inhibitors, Protein Synthesis,Synthesis Antagonist, Protein,Synthesis Inhibitor, Protein
D003513 Cycloheximide Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. Actidione,Cicloheximide
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose

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