Insulin enhances the bradykinin response in L8 rat skeletal myoblasts

被引:10
作者
Kudoh, A
Dietze, GJ
Rabito, SF
机构
[1] Cook Cty Hosp, Dept Anesthesiol & Pain Management, Chicago, IL 60612 USA
[2] Max Grundig Clin, Hypertens & Diabet Res Unit, Buehl, Germany
关键词
D O I
10.2337/diabetes.49.2.190
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Inhibitors of ACE/kininase II enhance insulin sensitivity, an action that is mediated in part by bradykinin (BK). We investigated whether insulin interacts with the BK receptor signaling to modulate the inositol 1,4,5-trisphosphate (IP3) response to BK in 18 rat skeletal myoblasts. Stimulation of the cultures with BR (10 nmol/l) for 15 s increased IP3 from a basal level of 75.2 +/- 7.6 to 200.2 +/- 15.7 pmol/mg protein. Treatment of the cultures with 1, 2, and 20 nmol/l of insulin for 90 min before adding BK increased IP3 formation by the same BK dose to 328.2 +/- 19, 434.5 +/- 18, and 460.8 +/- 21.3 pmol/mg protein, respectively. When wortmannin was administered to inhibit phosphatidylinositol (PI) 3-kinases at lower concentration (1 nmol/l), it increased IP3 formation stimulated by BK only when insulin was present. At a higher concentration (100 nmol/l), wortmannin significantly enhanced BK-induced IP3 formation in the absence of insulin. Genistein and tyrphostin A-23, tyrosine kinase inhibitors, completely reversed the elevated IP3 formation by BK and insulin. The IP3 response to 10 nmol/l BK was 223.3 +/- 11.8 pmol/mg protein in the absence of insulin and 402.2 +/- 12.0 pmol/mg protein in the presence of 2 nmol/l insulin. However, when exposing the cultures to 1 nmol/l genistein or tyrphostin A-23, the IP3 response to BK in the presence of insulin decreased to 211.8 +/- 46.7 and 187.7 +/- 19.9 pmol/mg protein. Tyrphostin A-1, the inactive analog, was ineffective. Exposing the cells to 1 mu mol/l 3,4,5-trimethoxybenzoic acid 8-[diethylamino]octyl ester, an intracellular Ca2+ antagonist, did not change the potentiation by insulin. But, exposing them to 0.1 mu mol/l n-[6-aminohexyl]-5- chloro-1-naphthalene-sulfonamide, a calmodulin antagonist, resulted in enhanced IP3 response to BK alone to 292.2 +/- 18.5 pmol/mg protein and to BK in the presence of 1, 2, and 20 nmol/l insulin to 488 +/- 22.2, 625.5 +/- 11.61 and 685.2 +/- 15.9 pmol/mg protein, respectively. In conclusion, insulin potentiates BK-induced IP3 production in 18 rat skeletal myoblasts, and this action of insulin involves a tyrosine kinase. Inhibition of PI Q-kinases potentiated BK-induced IP3 formation in the presence of insulin. Calmodulin blocked the action of insulin. These results support a modulatory effect of insulin on the BK signaling system via a tyrosine kinase in 18 rat skeletal myoblasts that results in increased IP3 formation. Because BK release from skeletal muscle increases during contractions, this action of insulin is likely to play a role in the modulation of the excitation-contraction coupling process of the skeletal muscle.
引用
收藏
页码:190 / 194
页数:5
相关论文
共 49 条
[1]   INOSITOL PHOSPHATES AND CELL SIGNALING [J].
BERRIDGE, MJ ;
IRVINE, RF .
NATURE, 1989, 341 (6239) :197-205
[2]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[3]  
Briand SI, 1996, J CELL BIOCHEM, V63, P292, DOI 10.1002/(SICI)1097-4644(19961201)63:3<292::AID-JCB4>3.3.CO
[4]  
2-Q
[5]   INSULIN ACTION AND THE INSULIN SIGNALING NETWORK [J].
CHEATHAM, B ;
KAHN, CR .
ENDOCRINE REVIEWS, 1995, 16 (02) :117-142
[6]   IMPROVED GLUCOSE-METABOLISM FOLLOWING BLOCKADE OF ANGIOTENSIN-CONVERTING ENZYME BUT NOT ANGIOTENSIN AT(1) RECEPTORS [J].
CHOW, L ;
DEGASPARO, M ;
LEVENS, N .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 282 (1-3) :77-86
[7]   Potential role of bradykinin in forearm muscle metabolism in humans [J].
Dietze, GJ ;
Wicklmayr, M ;
Rett, K ;
Jacob, S ;
Henriksen, EJ .
DIABETES, 1996, 45 :S110-S114
[8]   MODULATION OF THE ACTION OF INSULIN IN RELATION TO THE ENERGY-STATE IN SKELETAL-MUSCLE TISSUE - POSSIBLE INVOLVEMENT OF KININS AND PROSTAGLANDINS [J].
DIETZE, GJ .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1982, 25 (02) :127-149
[9]   INTRACELLULAR CONTROL OF INOSITOL PHOSPHATES BY THEIR METABOLIZING ENZYMES [J].
ERNEUX, C ;
TAKAZAWA, K .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1991, 12 (05) :174-176
[10]   Immunolocalization of bradykinin B-2 receptors on skeletal muscle cells [J].
Figueroa, CD ;
Dietze, G ;
MullerEsterl, W .
DIABETES, 1996, 45 :S24-S28