Anti diabetic effect of CL 316,243 (a β3-adrenergic agonist) by down regulation of tumour necrosis factor (TNF-α) expression.
OBJECTIVE
Obesity is a risk factor for the development of insulin resistance and is one of the most important contributors to the pathogenesis of type 2 diabetes, which acts mainly through the secretion of adipokines such as TNF-α that may influence insulin sensitivity. TNF-α affects many aspects of adipocyte function, such as adipocyte development and lipid metabolism.


METHODS
We demonstrated that there is a correlation between the expressions of TNF-α in retroperitoneal WAT and insulin-resistance in 8 genetically obese fa/fa rats. Treatment of animals with CL 316,243, a β3-adrenergic agonist, showed an improvement of insulin-resistance that was linked with the suppression of TNF-α mRNA expression in WAT.


RESULTS
These results confirm the association between TNF-α expression and the insulin-resistant condition in rats. Our finding indicates that the hyperglycaemia and hyperinsulinemia induced by insulin-resistance correlated positively with the expression of TNF-α mRNA in an abdominal WAT depot.


CONCLUSIONS
We conclude that CL 316,243 possesses both anti-diabetic effects and anti-obesity effects in rodents.
Department of Microbiology and Immunology, Pasteur Institute of Iran, Tehran, Iran. mghorbani@irimc.org
Masoud
M
Ghorbani
Mehdi
M
Shafiee Ardestani
Sedigheh Hatami
SH
Gigloo
Reza Ahangari
RA
Cohan
Davoud Nouri
DN
Inanlou
Peyman
P
Ghorbani
D050153:Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004149:Dioxoles / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005227:Fatty Acids / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000517:prevention & control; D051381:Rats; D011924:Rats, Zucker; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D004149:Dioxoles; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D022702:Receptors, Adrenergic, beta-3; D014409:Tumor Necrosis Factor-alpha; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate