Insulin regulation of pyruvate kinase activity in cultured rat hepatocytes, in the presence of vasopressin, ionophore A23187 or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate. 1988

R A Pittner, and J N Fain
Department of Biochemistry, University of Tennessee, Memphis 38163.

The short-term interactions of insulin and vasopressin on pyruvate kinase (PK) activity were studied in primary cultures of rat hepatocytes. (1) Vasopressin inhibited PK activity by approx. 30% within 15 s, but activity returned to control values by 5 min. The transient inhibition by vasopressin was mimicked by either 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) or ionophore A23187. (2) Insulin alone transiently inhibited PK activity at 1 min, but stimulated PK activity at 5 and 15 min. (3) Insulin completely antagonized the early inhibition by vasopressin, PMA or A23187 of PK activity at 15 s. (4) Insulin inhibited PK activity in the presence of vasopressin, PMA or A23187 at 5 min. (5) 8-Bromo cyclic AMP inhibited PK activity within 15 s, and this inhibition was maintained for at least 5 min. Insulin did not antagonized the inhibition by the cyclic AMP analogue. These results show that insulin under appropriate conditions can act as an inhibitor or activator of PK.

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
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D011770 Pyruvate Kinase ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40. L-Type Pyruvate Kinase,M-Type Pyruvate Kinase,M1-Type Pyruvate Kinase,M2-Type Pyruvate Kinase,Pyruvate Kinase L,R-Type Pyruvate Kinase,L Type Pyruvate Kinase,M Type Pyruvate Kinase,M1 Type Pyruvate Kinase,M2 Type Pyruvate Kinase,Pyruvate Kinase, L-Type,Pyruvate Kinase, M-Type,Pyruvate Kinase, M1-Type,Pyruvate Kinase, M2-Type,Pyruvate Kinase, R-Type,R Type Pyruvate Kinase
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D000001 Calcimycin An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems. 4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-((3,9,11-trimethyl-8-(1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl)-1,7-dioxaspiro(5.5)undec-2-yl)methyl)-, (6S-(6alpha(2S*,3S*),8beta(R*),9beta,11alpha))-,A-23187,A23187,Antibiotic A23187,A 23187,A23187, Antibiotic
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
D013755 Tetradecanoylphorbol Acetate A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA. Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer
D014667 Vasopressins Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure. Antidiuretic Hormone,Antidiuretic Hormones,beta-Hypophamine,Pitressin,Vasopressin,Vasopressin (USP),Hormone, Antidiuretic,beta Hypophamine
D015124 8-Bromo Cyclic Adenosine Monophosphate A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase. 8-Bromo-cAMP,8-Br Cyclic AMP,8-Bromo Cyclic AMP,8-Bromo Cyclic Adenosine Monophosphate, Monosodium Salt,8-Bromo Cyclic Adenosine Monophosphate, Sodium Salt,8-Bromoadenosine 3',5'-Cyclic Monophosphate,Br Cycl AMP,8 Br Cyclic AMP,8 Bromo Cyclic AMP,8 Bromo Cyclic Adenosine Monophosphate,8 Bromo Cyclic Adenosine Monophosphate, Monosodium Salt,8 Bromo Cyclic Adenosine Monophosphate, Sodium Salt,8 Bromo cAMP,8 Bromoadenosine 3',5' Cyclic Monophosphate,AMP, Br Cycl,Cyclic AMP, 8-Br,Cyclic AMP, 8-Bromo

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