PMID- 12086950
OWN - NLM
STAT- MEDLINE
DCOM- 20020726
LR  - 20220228
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 51
IP  - 7
DP  - 2002 Jul
TI  - Long-term AICAR administration reduces metabolic disturbances and lowers blood 
      pressure in rats displaying features of the insulin resistance syndrome.
PG  - 2199-206
AB  - The insulin resistance syndrome is characterized by several risk factors for 
      cardiovascular disease. Chronic chemical activation of AMP-activated protein 
      kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta 
      -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate 
      mitochondrial enzymes in skeletal muscles, and decrease the content of 
      intra-abdominal fat. Furthermore, acute AICAR exposure has been found to reduce 
      sterol and fatty acid synthesis in rat hepatocytes incubated in vitro as well as 
      suppress endogenous glucose production in rats under euglycemic clamp conditions. 
      To investigate whether chronic AICAR administration, in addition to the 
      beneficial effects on insulin sensitivity, is capable of improving other 
      phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) 
      rats (n = 6) exhibiting insulin resistance, hyperlipidemia, and hypertension were 
      subcutaneously injected with AICAR (0.5 mg/g body wt) daily for 7 weeks. Obese 
      control rats were either pair-fed (PF) (n = 6) or ad libitum-fed (AL) (n = 6). 
      Lean Zucker rats (fa/-) (n = 8) served as a reference group. AICAR administration 
      significantly reduced plasma triglyceride levels (P < 0.01 for AICAR vs. AL, and 
      P = 0.05 for AICAR vs. PF) and free fatty acids (P < 0.01 for AICAR vs. AL, and P 
      < 0.05 for AICAR vs. PF) and increased HDL cholesterol levels (P < 0.01 for AICAR 
      vs. AL and PF). AICAR treatment also lowered systolic blood pressure by 14.6 +/- 
      4.3 mmHg (P < 0.05), and AICAR-treated animals exhibited a tendency toward 
      decreased intra-abdominal fat content. Furthermore, AICAR administration 
      normalized the oral glucose tolerance test and decreased fasting concentrations 
      of glucose and insulin close to the level of the lean animals. Finally, in line 
      with previous findings, AICAR treatment was also found to enhance GLUT4 protein 
      expression and to increase maximally insulin-stimulated glucose transport in 
      primarily white fast-twitch muscles. Our data provide strong evidence that 
      long-term administration of AICAR improves glucose tolerance, improves the lipid 
      profile, and reduces systolic blood pressure in an insulin-resistant animal 
      model. The present study gives additional support to the hypothesis that AMPK 
      activation might be a potential future pharmacological strategy for treating the 
      insulin resistance syndrome.
FAU - Buhl, Esben S
AU  - Buhl ES
AD  - Medical Research Laboratory, Medical Department M (Endocrinology and Diabetes), 
      Aarhus University Hospital, Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark.
FAU - Jessen, Niels
AU  - Jessen N
FAU - Pold, Rasmus
AU  - Pold R
FAU - Ledet, Thomas
AU  - Ledet T
FAU - Flyvbjerg, Allan
AU  - Flyvbjerg A
FAU - Pedersen, Steen B
AU  - Pedersen SB
FAU - Pedersen, Oluf
AU  - Pedersen O
FAU - Schmitz, Ole
AU  - Schmitz O
FAU - Lund, Sten
AU  - Lund S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Ribonucleotides)
RN  - 0 (Slc2a4 protein, rat)
RN  - 146-72-5 (3-O-Methylglucose)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - 3-O-Methylglucose/pharmacokinetics
MH  - Adenylate Kinase/metabolism
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/*pharmacology
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Blood Pressure/*drug effects
MH  - Glucose Clamp Technique
MH  - Glucose Transporter Type 4
MH  - Hypertension/*drug therapy
MH  - Insulin Resistance/*physiology
MH  - Male
MH  - Metabolic Syndrome
MH  - Monosaccharide Transport Proteins/drug effects/metabolism
MH  - *Muscle Proteins
MH  - Rats
MH  - Rats, Zucker
MH  - Ribonucleotides/*pharmacology
MH  - Syndrome
EDAT- 2002/06/28 10:00
MHDA- 2002/07/27 10:01
CRDT- 2002/06/28 10:00
PHST- 2002/06/28 10:00 [pubmed]
PHST- 2002/07/27 10:01 [medline]
PHST- 2002/06/28 10:00 [entrez]
AID - 10.2337/diabetes.51.7.2199 [doi]
PST - ppublish
SO  - Diabetes. 2002 Jul;51(7):2199-206. doi: 10.2337/diabetes.51.7.2199.