ROLE OF PHOSPHODIESTERASE-III IN THE ANTILIPOLYTIC EFFECT OF INSULIN IN-VIVO

被引:32
作者
HAGSTROMTOFT, E
BOLINDER, J
ERIKSSON, S
ARNER, P
机构
[1] KAROLINSKA INST, HUDDINGE HOSP, DEPT MED, S-14186 HUDDINGE, SWEDEN
[2] HUDDINGE HOSP, KAROLINSKA INST, RES CTR, S-14186 HUDDINGE, SWEDEN
关键词
D O I
10.2337/diabetes.44.10.1170
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effect of three types of phosphodiesterase (PDE) inhibitors on in vivo antilipolysis was investigated in healthy subjects using a 2-h euglycemic, hyperinsulinemic (40 mU . m(-2). min) clamp together with microdialysis of abdominal subcutaneous adipose tissue. During hyperinsulinemia (similar to 330 pmol/l), the circulating glycerol concentration was reduced to similar to 50% of the basal level of 53.2 +/- 3.6 mu mol/l, indicating an antilipolytic effect, The decrease in adipose tissue dialysate glycerol, which mirrors the change in interstitial glycerol concentration, was about 40% during hyperinsulinemia when Ringer's solution alone was perfused, Local perfusion with a selective PDE IV inhibitor, rolipram (10(-4) mol/l), did not influence the insulin-induced decrease in dialysate glycerol (F = 0.8 vs, perfusion with Ringer's solution by two-factor analysis of variance [ANOVA]), although rolipram increased the dialysate glycerol level by 144 +/- 7% of the baseline value. However, local perfusion with a selective PDE III inhibitor, amrinone (10(-3) mol/l), or a nonselective PDE inhibitor, theophylline (10(-2) mol/l), abolished the ability of insulin to lower dialysate glycerol (F = 16,5, P < 0.01 and F = 8.5, P < 0.01, respectively, as compared with perfusion with Ringer's solution), The findings could not be explained by changes in the local blood flow Cas measured by a microdialysis-ethanol escape technique), which was not affected by hyperinsulinemia in the presence or the absence of PDE inhibitors in the dialysis solvent, We conclude that PDEs play an important role in mediating the antilipolytic effect of insulin in vivo and that PDE III is the dominant isoenzyme modulating this effect.
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页码:1170 / 1175
页数:6
相关论文
共 41 条
[1]   USE OF A HEATED SUPERFICIAL HAND VEIN AS AN ALTERNATIVE SITE FOR THE MEASUREMENT OF AMINO-ACID-CONCENTRATIONS AND FOR THE STUDY OF GLUCOSE AND ALANINE KINETICS IN MAN [J].
ABUMRAD, NN ;
RABIN, D ;
DIAMOND, MP ;
LACY, WW .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1981, 30 (09) :936-940
[2]  
AMER P, 1988, DIABETES METAB REV, V4, P507
[3]   ADRENERGIC REGULATION OF LIPOLYSIS INSITU AT REST AND DURING EXERCISE [J].
ARNER, P ;
KRIEGHOLM, E ;
ENGFELDT, P ;
BOLINDER, J .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (03) :893-898
[4]  
ARNER P, 1990, J PHARMACOL EXP THER, V254, P284
[5]  
ARNER P, 1993, J LIPID RES, V34, P1737
[6]   ONCOGENES AND SIGNAL TRANSDUCTION [J].
CANTLEY, LC ;
AUGER, KR ;
CARPENTER, C ;
DUCKWORTH, B ;
GRAZIANI, A ;
KAPELLER, R ;
SOLTOFF, S .
CELL, 1991, 64 (02) :281-302
[7]   POSTPRANDIAL SUBSTRATE DEPOSITION IN HUMAN FOREARM AND ADIPOSE TISSUES INVIVO [J].
COPPACK, SW ;
FISHER, RM ;
GIBBONS, GF ;
HUMPHREYS, SM ;
MCDONOUGH, MJ ;
POTTS, JL ;
FRAYN, KN .
CLINICAL SCIENCE, 1990, 79 (04) :339-348
[8]  
DEFRONZO RA, 1979, AM J PHYSIOL, V237, pE214
[9]  
EARL CQ, 1986, J CARDIOVASC PHARM, V8, P864
[10]  
ENGFELDT P, 1988, J BIOL CHEM, V263, P15553