PMID- 12215475
OWN - NLM
STAT- MEDLINE
DCOM- 20020911
LR  - 20220330
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 40
IP  - 3
DP  - 2002 Sep
TI  - ACE inhibitor improves insulin resistance in diabetic mouse via bradykinin and 
      NO.
PG  - 329-34
AB  - Improvement of insulin resistance by ACE inhibitors has been suggested; however, 
      this mechanism has not been proved. We postulated that activation of the 
      bradykinin-nitric oxide (NO) system by an ACE inhibitor enhances glucose uptake 
      in peripheral tissues by means of an increase in translocation of glucose 
      transporter 4 (GLUT4), resulting in improvement of insulin resistance. 
      Administration of an ACE inhibitor, temocapril, significantly decreased plasma 
      glucose and insulin concentrations in type 2 diabetic mouse KK-Ay. Mice treated 
      with temocapril showed a smaller plasma glucose increase after glucose load. We 
      demonstrated that temocapril treatment significantly enhanced 
      2-[3H]-deoxy-D-glucose (2-DG) uptake in skeletal muscle but not in white adipose 
      tissue. Administration of a bradykinin B2 receptor antagonist, Hoe140, or an NO 
      synthase inhibitor, L-NAME, attenuated the enhanced glucose uptake by temocapril. 
      Moreover, we observed that translocation of GLUT4 to the plasma membrane was 
      significantly enhanced by temocapril treatment without influencing insulin 
      receptor substrate-1 phosphorylation. In L6 skeletal muscle cells, 2-DG uptake 
      was increased by temocaprilat, and Hoe140 inhibited this effect of temocaprilat 
      but not that of insulin. These results suggest that temocapril would improve 
      insulin resistance and glucose intolerance through increasing glucose uptake, 
      especially in skeletal muscle at least in part through enhancement of the 
      bradykinin-NO system and consequently GLUT4 translocation.
FAU - Shiuchi, Tetsuya
AU  - Shiuchi T
AD  - Department of Medical Biochemistry, Ehime University School of Medicine, Ehime, 
      Japan.
FAU - Cui, Tai-Xing
AU  - Cui TX
FAU - Wu, Lan
AU  - Wu L
FAU - Nakagami, Hironori
AU  - Nakagami H
FAU - Takeda-Matsubara, Yuko
AU  - Takeda-Matsubara Y
FAU - Iwai, Masaru
AU  - Iwai M
FAU - Horiuchi, Masatsugu
AU  - Horiuchi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Blood Glucose)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Slc2a4 protein, mouse)
RN  - 0 (Thiazepines)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 8G820I95VP (temocapril hydrochloride)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Blood Glucose/analysis
MH  - Bradykinin/*physiology
MH  - Cell Line
MH  - Deoxyglucose/metabolism
MH  - Diabetes Mellitus, Type 2/drug therapy/*metabolism
MH  - Glucose Transporter Type 4
MH  - Insulin Receptor Substrate Proteins
MH  - *Insulin Resistance
MH  - Kinetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monosaccharide Transport Proteins/metabolism
MH  - *Muscle Proteins
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Nitric Oxide/*physiology
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Protein Transport/drug effects
MH  - Thiazepines/*pharmacology
EDAT- 2002/09/07 10:00
MHDA- 2002/09/12 10:01
CRDT- 2002/09/07 10:00
PHST- 2002/09/07 10:00 [pubmed]
PHST- 2002/09/12 10:01 [medline]
PHST- 2002/09/07 10:00 [entrez]
AID - 10.1161/01.hyp.0000028979.98877.0c [doi]
PST - ppublish
SO  - Hypertension. 2002 Sep;40(3):329-34. doi: 10.1161/01.hyp.0000028979.98877.0c.