Insulin secretion in adult rats after intrauterine exposure to mild hyperglycemia during late gestation.
We investigated the effects of intrauterine mild hyperglycemia during late fetal life on glucose regulation and insulin secretion in adult rats. Unrestrained pregnant rats were continuously infused with glucose during the last week of pregnancy to induce mild hyperglycemia (6.5-8 mM). Control rats were infused with a glucose-free solution. The offspring were studied, as adults, from 1 to 20 mo by performing glucose tolerance and insulin secretion tests. Young-adult rats from hyperglycemic dams showed mild glucose intolerance and impairment of glucose-induced insulin secretion. This situation gradually evolved to basal hyperglycemia and severe impairment of glucose tolerance and insulin secretion. Insulin secretion was also studied in vitro in 20-mo-old rats with the isolated perfused-pancreas technique. Insulin release in response to glucose stimulation from pancreases of hyperglycemic dams was similar to that of controls, and the response to arginine was increased but not significantly. The possible involvement of enhanced sympathetic nervous system activity in the impairment of insulin secretion in adult rats from hyperglycemic mothers was then investigated by performing glucose tolerance and insulin secretion tests in the presence of the alpha 2-blocker idazoxan in 8-mo-old rats. Under these conditions, rats from hyperglycemic dams recovered almost normal glucose tolerance, and glucose-induced insulin secretion was greatly improved. These data show that mild hyperglycemia induced in the fetus during late pregnancy leads to persistent impairment of glucose regulation and insulin secretion. They suggest that the impairment of insulin secretion in vivo results from a perturbation of the neuroregulation of insulin secretion rather than an intrinsic pancreatic beta-cell defect.
Laboratory of Developmental Physiology, Paris VII University, France.
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Gauguier
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Bihoreau
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Ktorza
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000503:physiopathology*; D019329:Idazoxan; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D004146:Dioxanes; D007328:Insulin; D019329:Idazoxan