Insulin-like Action of Proinsulin on Rat Liver Carbohydrate Metabolism In Vitro

Short-term effects of human proinsulin on metabolic rates and its long-term action on enzyme induction were studied in primary cultures of rat hepatocytes and in the perfused rat liver, and compared with the effects of bovine insulin. In the perfused rat liver, proinsulin decreased the glucagon-dependent increase of glycogenolysis. The action of 0.5 nM glucagon was almost completely suppressed by 100 nM proinsulin. Proinsulin and insulin showed similar potency. In cultured rat hepatocytes, proinsulin stimulated glycolysis up to fivefold with a half-maximal effective dose of 30 nM. Proinsulin induced the key glycolytic enzymes glucokinase and pyruvate kinase by twofold and antagonized the glucagon-dependent induction of phosphoenolpyruvate carboxykinase with a halfmaximal effective dose at 3 nM. For the effects in cultured hepatocytes, about 100-fold higher concentrations of proinsulin than of insulin were required.

[1]  K. Polonsky,et al.  The Effects of Biosynthetic Human Proinsulin on Carbohydrate Metabolism , 1984, Diabetes.

[2]  K. Polonsky,et al.  The metabolic effects of biosynthetic human proinsulin in individuals with type I diabetes. , 1984, The Journal of clinical endocrinology and metabolism.

[3]  J. Olefsky,et al.  In Vitro Characterization of Biosynthetic Human Proinsulin , 1984, Diabetes.

[4]  K. Jungermann,et al.  Short-term regulation of glycolysis by insulin and dexamethasone in cultured rat hepatocytes. , 1983, European journal of biochemistry.

[5]  H G Hers,et al.  Gluconeogenesis and related aspects of glycolysis. , 1983, Annual review of biochemistry.

[6]  M. Entman,et al.  Comparison of hepatic extraction of insulin and glucagon in conscious and anesthetized dogs. , 1983, Endocrinology.

[7]  K. Jungermann,et al.  Direct control of glycogen metabolism in the perfused rat liver by the sympathetic innervation. , 2005, European journal of biochemistry.

[8]  T. Tanaka,et al.  Regulation of rat liver L-type pyruvate kinase mRNA by insulin and by fructose. , 2005, European journal of biochemistry.

[9]  K. Jungermann,et al.  The glucose/glucose-6-phosphate cycle in the periportal and perivenous zone of rat liver. , 1982, European journal of biochemistry.

[10]  L. Hue,et al.  Short-Term Regulation of Liver Metabolism , 1982 .

[11]  K. Jungermann,et al.  Modulation of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and tyrosine aminotransferase by arterial and venous oxygen concentrations in hepatocyte cultures. , 1981, European journal of biochemistry.

[12]  P. Walter,et al.  Short-term stimulation of net glycogen production by insulin in rat hepatocytes. , 1981, Biochimica et biophysica acta.

[13]  H. Pitot,et al.  Role of insulin, glucose, and cyclic GMP in the regulation of glucokinase in cultured hepatocytes. , 1981, The Journal of biological chemistry.

[14]  W. Lautt.  Hepatic nerves: a review of their functions and effects. , 1980, Canadian journal of physiology and pharmacology.

[15]  N. Katz,et al.  Induction of glucokinase by insulin under the permissive action of dexamethasone in primary rat hepatocyte cultures. , 1979, Biochemical and biophysical research communications.

[16]  H. Pitot,et al.  Hormonal regulation of phosphoenolpyruvate carboxykinase in primary cultures of adult-rat liver parenchymal cells. , 1978, European journal of biochemistry.

[17]  W. Blackard,et al.  Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. , 1975, The Journal of clinical investigation.

[18]  P. Freychet.  The interactions of proinsulin with insulin receptors on the plasma membrane of the liver. , 1974, The Journal of clinical investigation.

[19]  P. Sönksen,et al.  A comparative study on the metabolism of human insulin and porcine proinsulin in man. , 1973, Clinical science and molecular medicine.

[20]  A. Katz,et al.  Metabolism of proinsulin, insulin, and C-peptide in the rat. , 1973, The Journal of clinical investigation.

[21]  D. Dhumeaux,et al.  Measurement of hepatic blood flow in the rat. Trans-hepatic catheterization of the hepatic veins. , 1973, Biologie et gastro-enterologie.

[22]  D. Steiner,et al.  The metabolism of proinsulin and insulin by the liver. , 1972, The Journal of clinical investigation.

[23]  J. Roth,et al.  Proinsulin-like component of circulating insulin in the basal state and in patients and hamsters with islet cell tumors. , 1971, The Journal of clinical investigation.

[24]  J Roth,et al.  Insulin receptors in the liver: specific binding of ( 125 I)insulin to the plasma membrane and its relation to insulin bioactivity. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[25]  N. Lazarus,et al.  Studies on the biological activity of porcine proinsulin. , 1970, The Journal of clinical investigation.

[26]  H. Söling,et al.  LACK OF HYPOGLYCEMIC EFFECT OF BOVINE PROINSULIN IN EVISCERATED, HEPATECTOMIZED RATS , 1969, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[27]  R. Chance,et al.  Effect of Porcine Proinsulin in Vitro on Adipose Tissue and Diaphragm of the Normal Rat , 1968, Diabetes.

[28]  R. Chance,et al.  Porcine Proinsulin: Characterization and Amino Acid Sequence , 1968, Science.

[29]  D. Steiner,et al.  Insulin Biosynthesis: Evidence for a Precursor , 1967, Science.

[30]  W. Seubert,et al.  On the mechanism of gluconeogenesis and its regulation. II. The mechanism of gluconeogenesis from pyruvate and fumarate. , 1965, Biochemische Zeitschrift.