Hyperinsulinemia of the genetically obese (fa/fa) rat is decreased by a low dose of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).
Changes in glycemia and insulinemia were determined in conscious lean (FA/?) and obese (fa/fa) rats after acute administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The intravenous injection of a low dose of 8-OH-DPAT (150 micrograms/kg) to lean rats rapidly promoted hyperglycemia. This modification was associated with a slight increase in insulinemia. The injection of 8-OH-DPAT markedly decreased basal hyperinsulinemia in obese rats while inducing hyperglycemia. Further evidence of the strong inhibitory effect of 8-OH-DPAT on insulin release was obtained in lean and obese rats during glucose tolerance tests. Intracerebroventricular injection of 8-OH-DPAT (45 micrograms/animal) triggered hyperglycemia and markedly decreased insulinemia in both lean and obese rats. This hypoinsulinemic effect of 8-OH-DPAT was more pronounced in the obese than in the lean animals. Measurement of the food intake elicited by 8-OH-DPAT (500 micrograms/kg s.c.) showed that the hyperphagic action of the 5-HT1A agonist was the same in FA/? and fa/fa rats. It is suggested that: (i) hyperinsulinemia of the genetically obese rat may be diminished by a low dose of 8-OH-DPAT; (ii) 5-HT1A autoreceptor-mediated regulation of serotonergic activity is not different in lean (FA/?) and obese (fa/fa) rats; (iii) 8-OH-DPAT could be of potential therapeutic use for some aspects of the pathology of type II diabetes.
Chaouloff
F
F
Laboratoire de Pharmacologie, INSERM U7, CHU Necker-Enfants Malades, Paris, France.
Jeanrenaud
B
B
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009765:Obesity / Q000097:blood* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005947:Glucose