Intrauterine hyperglycemia increases insulin binding sites but not glucose transporter expression in discrete brain areas in term rat fetuses.
Diabetic pregnancy results in several metabolic and hormonal disorders, both in the embryo and the fetus of different species, including humans. Insulin is a potent modulator of brain development and is suggested to promote the differentiation and maturation of hypothalamic or related extrahypothalamic structures, which are directly involved in neural inputs to the pancreas. Because these structures are known to be specifically responsive both to insulin and glucose, we examined the effects of 48-h hyperglycemic clamps in unrestrained pregnant rats on insulin binding and glucose transporter expression in hypothalamic and extrahypothalamic-related areas of their fetal offspring. The main result was an increase in insulin binding in the ventromedial hypothalamic nucleus (VMH), the arcuate nucleus (AN), and the lateral hypothalamus (LH), and in the nucleus of the tractus solitarius (NTS) for extrahypothalamic areas (+30% in the VMH, +37% in the AN, +25.8% in the LH, and +37.3% in the NTS). The deleterious effect of brain hyperinsulinism during the late gestational stage does not seem to act through glucose transporter (GLUT) expression, inasmuch as no relationship between GLUT level and hyperinsulinism in brain areas could be observed. The specific increase in insulin binding in areas involved in the nervous control of metabolism could be a factor in the increased glucose intolerance and impairment of insulin secretion that was previously observed in the adult rats from hyperglycemic mothers.
Leloup
Corinne
C
CNRS UMR 5018-UPS, CHU de Rangueil, 1 Ave Jean Poulhès, 31 403 Toulouse cedex, France. coleloup@toulouse.inserm.fr
Magnan
Christophe
C
Alquier
Thierry
T
Mistry
Sanjay
S
Offer
Géraldine
G
Arnaud
Emmanuelle
E
Kassis
Nadim
N
Ktorza
Alain
A
Pénicaud
Luc
L
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D016640:Diabetes, Gestational / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia; D007328:Insulin / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000378:metabolism*
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005947:Glucose