The fetus of a diabetic mother (FDM) is at increased risk for morbidity and mortality. Although it is acknowledged that these risks relate directly or indirectly to various metabolic problems associated with maternal carbohydrate intolerance, the precise mechanisms which underlie poor outcome in FDM are not understood clearly. We plan to study in chronic sheep diabetes models a complex of related fetal metabolic and neural and hormonal factors. Our own work and the work of others have shown hypoxemia to be a characteristic feature of experimental hyperinsulinemia and hyperglycemia in fetal sheep. We propose to study the potential roles of certain fetal neural and hormonal factors (sympathoadrenal, thyroid, and adrenocortical) in mediating this hypoxemia. In fetal sheep with chronic peripheral catheters and a chronic adrenal cannula, we will observe the states of these neural and hormonal systems in concurrence with the hypoxemia of altered fetal glucose-insulin metabolism. Further, we will observe the effects of individual ablation of these systems on fetal oxygenation and metabolism in response to maternal diabetes. Both clinical and experimental evidence suggests a harmful effect of uncontrolled maternal diabetes on the development of the endocrine pancreas in the fetus. In this area we plan to study the effect of streptozocin-induced diabetes in pregnant ewes on the insulin secretory function of the fetus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK039178-03
Application #
3238919
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1987-07-15
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Brown University
Department
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Jackson, B T; Piasecki, G J; Cohn, H E et al. (2000) Control of fetal insulin secretion. Am J Physiol Regul Integr Comp Physiol 279:R2179-88
Jackson, B T; Cohn, H E; Morrison, S H et al. (1993) Hypoxia-induced sympathetic inhibition of the fetal plasma insulin response to hyperglycemia. Diabetes 42:1621-5
Cohn, H E; Cohen, W R; Piasecki, G J et al. (1992) The effect of hyperglycemia on acid-base and sympathoadrenal responses in the hypoxemic fetal monkey. J Dev Physiol 17:299-304
Jackson, B T; Lee, A F; Morrison, S H et al. (1992) Adrenal corticosteroid secretion in fetal sheep: pulsatile pattern at rest. Am J Physiol 263:R936-44
Cohen, W R; Piasecki, G J; Cohn, H E et al. (1991) Sympathoadrenal responses during hypoglycemia, hyperinsulinemia, and hypoxemia in the ovine fetus. Am J Physiol 261:E95-102
Jackson, B T; Morrison, S H; Cohn, H E et al. (1989) Adrenal secretion of glucocorticoids during hypoxemia in fetal sheep. Endocrinology 125:2751-7