The Relationship Between the Concentration of Adenosine 3':5'-cyclic Monophosphate and the Anti-lipolytic Action of Insulin in Isolated Rat Fat-cells

Overview

Journal Biochem J

Specialty Biochemistry

Date 1974 Jul 1

PMID 4374189

Citations 5

Authors

K Siddle

C N Hales

Affiliations

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Abstract

The relationship between cyclic AMP content and lipolysis, as measured by glycerol formation, was studied in isolated rat fat-cells. Inhibition of lipolysis by insulin in the presence of a low concentration of adrenaline was accompanied by little or no lowering of cyclic AMP content, measured after 15min incubation. The time-course of cyclic AMP content after addition of adrenaline showed that the effect of insulin in lowering cyclic AMP content measured after 2-5min was gradually lost over the next hour, mainly because of the fall in cyclic AMP content after an early peak in the presence of adrenaline alone. There was a 44% loss of immunoreactive insulin, from an initial concentration of 0.3nm, during a 1h incubation with fat-cells. Insulin did not affect partitioning of cyclic AMP between cells and incubation medium. When the correlation between cyclic AMP content and rate of lipolysis was investigated for a wide range of adrenaline concentrations, it was found that the lowering of cyclic AMP content by insulin was much less than that required to account for the amount of inhibition of lipolysis. It is concluded that inhibition of adrenaline-stimulated lipolysis by insulin involves factors in addition to a decrease in intracellular cyclic AMP concentration.

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References

Efendic S, Alm B, Low H . Effects of Ca ++ on lipolysis in human omental adipose tissue in vitro. Horm Metab Res. 1970; 2(5):287-91. View

Ho R, SUTHERLAND E . Formation and release of a hormone antagonist by rat adipocytes. J Biol Chem. 1971; 246(22):6822-7. View

Butcher R, Baird C, SUTHERLAND E . Effects of lipolytic and antilipolytic substances on adenosine 3',5'-monophosphate levels in isolated fat cells. J Biol Chem. 1968; 243(8):1705-12. View

Werner S, Alm B, Low H . Effects of adrenalectomy and resubstitution with moderate and high doses of cortisone acetate on lipolysis and 47 calcium uptake in rat adipose tissue in vivo. Horm Metab Res. 1972; 4(3):195-201. DOI: 10.1055/s-0028-1094048. View

Schonhofer P, SKIDMORE I, Krishna G . Effects of insulin on the lipolytic system of rat fat cells. Horm Metab Res. 1972; 4(6):447-54. DOI: 10.1055/s-0028-1094003. View

HUTTUNEN J, Steinberg D . Activation and phosphorylation of purified adipose tissue hormone-sensitive lipase by cyclic AMP-dependent protein kinase. Biochim Biophys Acta. 1971; 239(3):411-27. DOI: 10.1016/0005-2760(71)90034-8. View

Corbin J, Soderling T, Park C . Regulation of adenosine 3',5'-monophosphate-dependent protein kinase. I. Preliminary characterization of the adipose tissue enzyme in crude extracts. J Biol Chem. 1973; 248(5):1813-21. View

Crofford O, Rogers N, Russell W . The effect of insulin on fat cells. An insulin degrading system extracted from plasma membranes of insulin responsive cells. Diabetes. 1972; 21(2 Suppl):403-13. DOI: 10.2337/diab.21.2.s403. View

Kuo J, DE RENZO E . A comparison of the effects of lipolytic and antilipolytic agents on adenosine 3',5'-monophosphate levels in adipose cells as determined by prior labeling with adenine-8-14C. J Biol Chem. 1969; 244(9):2252-60. View

10.

EXTON J, Friedmann N, Wong E, Brineaux J, Corbin J, Park C . Interaction of glucocorticoids with glucagon and epinephrine in the control of gluconeogenesis and glycogenolysis in liver and of lipolysis in adipose tissue. J Biol Chem. 1972; 247(11):3579-88. View

11.

Khoo J, Steinberg D, Thompson B, Mayer S . Hormonal regulation of adipocyte enzymes. The effects of epinephrine and insulin on the control of lipase, phosphorylase kinase, phosphorylase, and glycogen synthase. J Biol Chem. 1973; 248(11):3823-30. View

12.

Soderling T, Corbin J, Park C . Regulation of adenosine 3',5'-monophosphate-dependent protein kinase. II. Hormonal regulation of the adipose tissue enzyme. J Biol Chem. 1973; 248(5):1822-9. View

13.

Loten E, SNEYD J . An effect of insulin on adipose-tissue adenosine 3':5'-cyclic monophosphate phosphodiesterase. Biochem J. 1970; 120(1):187-93. PMC: 1179583. DOI: 10.1042/bj1200187. View

14.

Hales C, Randle P . Immunoassay of insulin with insulin-antibody precipitate. Biochem J. 1963; 88:137-46. PMC: 1203862. DOI: 10.1042/bj0880137. View

15.

Siddle K, Campbell A . The effects of glucagon and insulin on adenosine 3':5'-cyclic monophosphate concentrations in an organ culture of mature rat liver. Biochem J. 1973; 132(4):765-73. PMC: 1177651. DOI: 10.1042/bj1320765. View

16.

Steiner A, KIPNIS D, UTIGER R, Parker C . Radioimmunoassay for the measurement of adenosine 3',5'-cyclic phosphate. Proc Natl Acad Sci U S A. 1969; 64(1):367-73. PMC: 286171. DOI: 10.1073/pnas.64.1.367. View

17.

Jungas R, BALL E . Studies on the metabolism of adipose tissue. XII. The effects of insulin and epinephrine on free fatty acid and glycerol production in the presence and absence of glucose. Biochemistry. 1963; 2:383-8. DOI: 10.1021/bi00902a035. View

18.

Martin B, Denton R, Pask H, Randle P . Mechanisms regulating adipose-tissue pyruvate dehydrogenase. Biochem J. 1972; 129(3):763-73. PMC: 1174178. DOI: 10.1042/bj1290763. View

19.

Kono T, Barham F . Effects of insulin on the levels of adenosine 3':5'-monophosphate and lipolysis in isolated rat epididymal fat cells. J Biol Chem. 1973; 248(21):7417-26. View

20.

JARETT L, Steiner A, Smith R, KIPNIS D . The involvement of cyclic AMP in the hormonal regulation of protein synthesis in rat adipocytes. Endocrinology. 1972; 90(5):1277-84. DOI: 10.1210/endo-90-5-1277. View