BIOMAT Database Logo BIOMAT Database Logo

Insulin regulates leptin secretion from 3T3-L1 adipocytes by a PI 3 kinase independent mechanism. 2008

Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Department of Molecular Genetics, The Rockefeller University, New York, NY 10021, USA.

To better define the molecular mechanisms underlying leptin release from adipocytes, we developed a novel protocol that maximizes leptin production from 3T3-L1 adipocytes. The addition of a PPARgamma agonist to the Isobutylmethylxanthine/Dexamethasone/Insulin differentiation cocktail increased leptin mRNA levels by 5-fold, maintained insulin sensitivity, and yielded mature phenotype in cultured adipocytes. Under these conditions, acute insulin stimulation for 2 h induced a two-fold increase in leptin secretion, which was independent of new protein synthesis, and was not due to alterations in glucose metabolism. Stimulation with insulin for 15 min induced the same level of leptin release and was blocked by Brefeldin A. Inhibiting PI 3-kinase with wortmannin had no effect on insulin stimulation of leptin secretion. These studies show that insulin can stimulate leptin release via a PI3K independent mechanism and provide a cellular system for studying the effect of insulin and potentially other mediators on leptin secretion.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
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
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D003470 Culture Media Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN. Media, Culture
D003513 Cycloheximide Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. Actidione,Cicloheximide
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
D000077191 Wortmannin An androstadiene metabolite produced by the fungi PENICILLIUM funiculosum that inhibits PHOSPHATIDYLINOSITOL-3-KINASES and alloantigen-specific activation of T-LYMPHOCYTES in human tumor cell lines. It is widely used in CELL BIOLOGY research and has broad therapeutic potential. MS 54,MS-54,MS54
D000081082 Phosphoinositide-3 Kinase Inhibitors Agents that inhibit PHOSPHOINOSITIDE-3 KINASE activity. Phosphoinositide-3 Kinase Inhibitor,Inhibitor, Phosphoinositide-3 Kinase,Inhibitors, Phosphoinositide-3 Kinase,Kinase Inhibitor, Phosphoinositide-3,Kinase Inhibitors, Phosphoinositide-3,Phosphoinositide 3 Kinase Inhibitor,Phosphoinositide 3 Kinase Inhibitors
D000730 Androstadienes Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Insulin activates phospholipase C-gamma1 via a PI-3 kinase dependent mechanism in 3T3-L1 adipocytes.
March 2001, Biochemical and biophysical research communications,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Angiotensin II increases leptin secretion by 3T3-L1 and human adipocytes via a prostaglandin-independent mechanism.
June 2002, The Journal of nutrition,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Insulin activates glycogen synthase by a novel PI 3-kinase/p70s6k dependent pathway in 3T3-L1 adipocytes.
May 1995, Biochemical Society transactions,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Activation of PI 3-kinase in 3T3-L1 adipocytes by association with insulin receptor substrate-1.
March 1994, The American journal of physiology,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Roles of PI 3-kinase and Ras on insulin-stimulated glucose transport in 3T3-L1 adipocytes.
February 1997, The American journal of physiology,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Insulin stimulates mitogen-activated protein kinase by a Ras-independent pathway in 3T3-L1 adipocytes.
November 1996, The Journal of biological chemistry,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Glucose-containing peritoneal dialysis fluids regulate leptin secretion from 3T3-L1 adipocytes.
July 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Insulin promotes formation of polymerized microtubules by a phosphatidylinositol 3-kinase-independent, actin-dependent pathway in 3T3-L1 adipocytes.
November 2003, Endocrinology,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Pioglitazone promotes insulin-induced activation of phosphoinositide 3-kinase in 3T3-L1 adipocytes by inhibiting a negative control mechanism.
July 1994, Molecular and cellular endocrinology,
Anja Zeigerer, and Matthew S Rodeheffer, and Timothy E McGraw, and Jeffrey M Friedman
Pioglitazone promotes insulin-induced activation of phosphoinositide 3-kinase in 3T3-L1 adipocytes by inhibiting a negative control mechanism.
June 1994, Molecular and cellular endocrinology,
Copied contents to your clipboard!