THE EFFECTS OF INSULIN ON THE GROWTH RATE OF THE SHEEP FETUS DURING LATE GESTATION

¹ Physiological Laboratory, Downing Street, Cambridge CB2 3EG

The effects of insulin on fetal growth rates were investigated by measuring crown-rump length (CRL) chronically in sheep fetuses before and after pancreatectomy, sham operation or pancreatectomy accompanied by insulin-replacement treatment. Pancreatectomy of the fetus produced hypoinsulinaemia and reduced the daily and total increments in CRL by 40-50% over the last 20-30 days of gestation. The growth rate fell immediately after pancreatectomy and remained low throughout the rest of gestation. In contrast to the sham-operated fetus no pre-partum decline in the growth rate was observed in the pancreatectomized animal. The body weight, limb lengths and actual CRL at delivery were also significantly less after pancreatectomy than in the sham-operated animals. When fetal insulin levels were maintained after pancreatectomy by exogenous insulin infusion, the daily and total increments in CRL and the body size at delivery were restored to their normal values. Raising insulin levels above normal in the pancreatectomized fetus did not lead to additional fetal growth. When the data from all the fetuses were combined irrespective of treatment, there were significant positive correlations between the plasma insulin concentration in utero and the mean daily increment in CRL after treatment and between the former value and the body weight at delivery. These observations demonstrate that insulin is a major determinant of the growth rate in utero and that it is required throughout late gestation for the normal growth and development of the sheep fetus. They also indicate that insulin deficiency is probably the primary cause of the growth retardation observed after fetal pancreatectomy.

This article has been cited by other articles:

				A. L. Fowden and A. J. Forhead Effects of Pituitary Hormone Deficiency on Growth and Glucose Metabolism of the Sheep Fetus Endocrinology, October 1, 2007; 148(10): 4812 - 4820. [Abstract] [Full Text] [PDF]

				P. D. Gluckman and C. S. Pinal Regulation of Fetal Growth by the Somatotrophic Axis J. Nutr., May 1, 2003; 133(5): 1741S - 1746. [Abstract] [Full Text] [PDF]

				T. R. H. Regnault, S. W. Limesand, and W. W. Hay Jr Factors Influencing Fetal Growth NeoReviews, June 1, 2001; 2(6): e119 - 128. [Full Text] [PDF]

				P. W. Nathanielsz Fetal Programming: How the Quality of Fetal Life Alters Biology for a Lifetime NeoReviews, July 1, 2000; 1(7): e126 - 131. [Full Text]

				J. M. Bassett and C. Hanson Prevention of hypoinsulinemia modifies catecholamine effects in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1171 - R1181. [Abstract] [Full Text] [PDF]

				E. A. Liechty and S. C. Denne Regulation of Fetal Amino Acid Metabolism: Substrate or Hormonal Regulation? J. Nutr., February 1, 1998; 128(2): 342 - 342. [Abstract] [Full Text]