Abstract |
The mechanism by which the specific beta3-adrenoceptor agonist AJ-9677 relieves insulin resistance in vivo was investigated by studying its effects in the white and brown adipose tissues of the KK-Ay/Ta diabetic obese mouse model. AJ-9677 reduced the total weight of white adipose tissues by reducing the size of the adipocytes, an effect associated with the normalization of tumor necrosis factor-alpha ( TNF-alpha) and leptin expression levels. The levels of uncoupling protein (UCP)-1 mRNA in brown adipose tissue were increased threefold. AJ-9677 caused a marked increase (20- to 80-fold) in the expression of UCP-1 in white adipose tissues. The levels of UCP-2 mRNA were increased in both the white and brown adipose tissues of diabetic obese mice, and AJ-9677 further upregulated UCP-2 mRNA levels in brown adipose tissue, but reduced its levels in white adipose tissue. UCP-3 mRNA levels were not essentially changed by AJ-9677. However, AJ-9677 significantly (two- to four-fold) upregulated the GLUT4 mRNA and protein levels in white and brown adipose tissues and the gastrocnemius. The generation of small adipocytes, presumably mediated by increased expression of UCP-1 in addition to increased lipolysis in response to AJ-9677, was associated with decreased TNF-alpha and free fatty acid production and may be the mechanism of amelioration of insulin resistance in KK-Ay/Ta diabetic obese mice.
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Authors | H Kato, M Ohue, K Kato, A Nomura, K Toyosawa, Y Furutani, S Kimura, T Kadowaki |
Journal | Diabetes
(Diabetes)
Vol. 50
Issue 1
Pg. 113-22
(Jan 2001)
ISSN: 0012-1797 [Print] United States |
PMID | 11147775
(Publication Type: Journal Article)
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Chemical References |
- ((3-((2R)-(((2R)-3-chlorophenyl)-2-hydroxyethyl)amino)propyl)-1H-indol-7-yloxy)acetic acid
- Acetates
- Adrenergic beta-Agonists
- Blood Glucose
- Carrier Proteins
- Fatty Acids, Nonesterified
- Glucose Transporter Type 4
- Indoles
- Insulin
- Ion Channels
- Leptin
- Membrane Proteins
- Membrane Transport Proteins
- Mitochondrial Proteins
- Monosaccharide Transport Proteins
- Muscle Proteins
- Proteins
- RNA, Messenger
- Slc2a4 protein, mouse
- Triglycerides
- Tumor Necrosis Factor-alpha
- Ucp1 protein, mouse
- Ucp2 protein, mouse
- Ucp3 protein, mouse
- Uncoupling Protein 1
- Uncoupling Protein 2
- Uncoupling Protein 3
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Topics |
- Acetates
- Adipose Tissue
(drug effects, pathology)
- Adrenergic beta-Agonists
(pharmacology)
- Animals
- Blood Glucose
(analysis)
- Carrier Proteins
(metabolism)
- Diabetes Mellitus
(genetics, pathology, physiopathology)
- Fatty Acids, Nonesterified
(blood)
- Glucose Transporter Type 4
- Indoles
(pharmacology)
- Insulin
(blood)
- Insulin Resistance
- Ion Channels
- Leptin
(genetics, metabolism)
- Membrane Proteins
(metabolism)
- Membrane Transport Proteins
- Mice
- Mitochondrial Proteins
- Monosaccharide Transport Proteins
(metabolism)
- Muscle Proteins
- Obesity
- Proteins
(metabolism)
- RNA, Messenger
(metabolism)
- Triglycerides
(blood)
- Tumor Necrosis Factor-alpha
(genetics, metabolism)
- Uncoupling Protein 1
- Uncoupling Protein 2
- Uncoupling Protein 3
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