# PERINATAL STUDIES OF DISORDERS OF FETAL METABOLISM

> **NIH NIH P50** · CASE WESTERN RESERVE UNIVERSITY · 1994 · $725,926

## Abstract

The long range objective of this application is to address an important
biologic question:  metabolic regulation of growth.  It is hypothesized
that the maternal metabolic environment, i.e. physiologic adaptation or
perturbations due to nutrient modification or disease process (diabetes
mellitus), regulates fetal growth.  The proposed hypotheses are based
upon data generated in the investigators' laboratories or in the PERC.
State-of-the-art techniques, genetic and molecular biology in animal
models, and stable isotope, mass spectrometry in humans will be applied.
The proposed studies are a continuum documenting the maternal influences
on fetal growth and neonatal adaptation, the fetal influence on maternal
metabolism, and the long term consequences of fetal and neonatal
metabolic/nutrient perturbations.  Six projects are presented.  The first
two examine, in humans, the changes in maternal glucose and amino acid
metabolism, resistance to insulin action and their relation to
fetal/placental growth, and alterations in infants' growth and
carbohydrate metabolism during the first year.  It is hypothesized that
insulin resistance and metabolism of non-essential amino acids may be
important determinants of fetal growth.  Project #3 examines the role of
two environmental factors (diet and physical activity) and two hormones
(HPL and fetal insulin) in placental growth.  This study examines the
hypothesis that early placental growth is a key determinant of fetal
growth.  Project #4 examines the mechanisms responsible for the metabolic
"imprinting" observed with early nutrient intervention in neonatal rat
and extends the in-utero studies to the neonate.  Project #5 examines the
role of fetal insulin and human placental lactogen on fetal growth and
metabolism in a binary transgenic mouse model.  Project #6 examines a key
event in relation to extrauterine adaptation and survival, i.e.
appearance of hepatic gluconeogenesis by evaluating the factors
responsible, e.g. nutrient supply, hepatic redox state, for the
patterning of expression of the genes for cytosolic form of P-
enolpyruvate carboxykinase.  All projects are scientifically interactive,
complement each other and utilize the core laboratories.  The mechanistic
questions are being addressed using sophisticated modern technologies in
animal models.  These studies will contribute to our understanding of
metabolic/hormonal regulation of fetal growth and help develop
therapeutic strategies for the disease states.

## Key facts

- **NIH application ID:** 2196774
- **Project number:** 5P50HD011089-17
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** SATISH C KALHAN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $725,926
- **Award type:** 5
- **Project period:** 1977-07-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196774

## Citation

> US National Institutes of Health, RePORTER application 2196774, PERINATAL STUDIES OF DISORDERS OF FETAL METABOLISM (5P50HD011089-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196774. Licensed CC0.

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