Effects of insulin on brain monoamine metabolism in the Zucker rat: influence of genotype and age.
Disturbances of insulin or brain monoamine metabolism may play a role in the impaired regulation of food intake and body weight in the obese Zucker rat. We investigated a possible insulin-monoamine interaction by measuring monoamine levels in the hypothalamus and striatum of obese (fa-fa) and lean (Fa-Fa and Fa-fa) Zucker rats after peripheral insulin administration. The classically reported effects of insulin, i.e., increases in tryptophan, 5-hydroxy-indolacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC) levels, were observed in the hypothalamus of Fa-Fa and Fa-fa rats, but not in obese fa-fa rats. Given the mechanism of action of insulin, this lack of effect in the obese rats may be related to the peripheral insulin resistance they exhibit. Furthermore, given the role of these monoaminergic systems, this reduced effect may be related to the impaired regulation of food intake and body weight. At 8 wk of age, however, insulin restored the decreased basal 5-HIAA levels observed in the obese rats. Increase in 5-HIAA levels following insulin administration appeared in the striatum of Fa-Fa rats only, suggesting that, as for brain insulin content, other central insulin-related disturbances may be related to the presence of the "fa" gene. In addition, certain effects of insulin on striatal dopamine release were observed in only the Fa-Fa and fa-fa rats, suggesting a particular disturbance related to the heterozygous character. This latter point calls for further investigations on the central dopaminergic effects of insulin.
Orosco
M
M
Université Paris-Sud, URA-CNRS 594, Laboratoire de Pharmacologie, Faculté de Pharmacie, Châtenay-Malabry, France.
Rouch
C
C
Gripois
D
D
Blouquit
M F
MF
Roffi
J
J
Jacquot
C
C
Cohen
Y
Y
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D003342:Corpus Striatum / Q000737:chemistry; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005260:Female; D005838:Genotype; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism; D007328:Insulin / Q000032:analysis / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D009765:Obesity / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker / Q000378:metabolism*; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D014364:Tryptophan / Q000032:analysis / Q000378:metabolism
D015306:Biogenic Monoamines; D001786:Blood Glucose; D007328:Insulin; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D004298:Dopamine