| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received June 17, 2002
Accepted after revision September 6, 2002
1 Perinatal Research Center, Division of Perinatal Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
2 Perinatal Research Center, University of Colorado Health Sciences Center, 13243 East 23rd Avenue (Bldg. 260), MS F441, Aurora, CO 80010, USA
* To whom correspondence should be addressed. E-mail: Bill.Hay{at}UCHSC.edu.
Fetal pancreatic adaptations to relative hypoglycaemia, a characteristic of intra-uterine growth restriction, may limit pancreatic ß-cell capacity to produce and/or secrete insulin. The objective of this study was to measure ß-cell responsiveness in hypoglycaemic (H) fetal sheep and ascertain whether a 5 day euglycaemic recovery period would restore insulin secretion capacity. Glucose-stimulated insulin secretion (GSIS) was measured in euglycaemic (E) control fetuses, fetuses made hypoglycaemic for 14 days, and in a subset of 14 day hypoglycaemic fetuses returned to euglycaemia for 5 days (R fetuses). Hypoglycaemia significantly decreased plasma insulin concentrations in H (0.13 ± 0.01 ng ml-1) and R fetuses (0.11 ± 0.01 ng ml-1); insulin concentrations returned to euglycaemic control values (0.30 ± 0.01 ng ml-1) in R fetuses (0.29 ± 0.04 ng ml-1) during their euglycaemic recovery period. Mean steady-state plasma insulin concentration during the GSIS study was reduced in H fetuses (0.40 ± 0.07 vs. 0.92 ± 0.10 ng ml-1 in E), but increased (P < 0.05) in R fetuses (0.73 ± 0.10 ng ml-1) to concentrations not different from those in the E group. Nonlinear modelling of GSIS showed that response time was greater (P < 0.01) in both H (15.6 ± 2.8 min) and R (15.4 ± 1.5 min) than in E fetuses (6.3 ± 1.1 min). In addition, insulin secretion responsiveness to arginine was reduced by hypoglycaemia (0.98 ± 0.11 ng ml-1 in H vs. 1.82 ± 0.17 ng ml-1 in E, P < 0.05) and did not recover (1.21 ± 0.15 ng ml-1 in R, P < 0.05 vs. E). Thus, a 5 day euglycaemic recovery period from chronic hypoglycaemia reestablished GSIS to normal levels, but there was a persistent reduction of ß-cell responsiveness to glucose and arginine. We conclude that programming of pancreatic insulin secretion responsiveness can occur in response to fetal glucose deprivation, indicating a possible mechanism for establishing, in fetal life, a predisposition to type 2 diabetes.
This article has been cited by other articles:
|
|
 |
|
  P. J. Rozance, S. W. Limesand, J. S. Barry, L. D. Brown, S. R. Thorn, D. LoTurco, T. R. H. Regnault, J. E. Friedman, and W. W. Hay Jr. Chronic late-gestation hypoglycemia upregulates hepatic PEPCK associated with increased PGC1{alpha} mRNA and phosphorylated CREB in fetal sheep Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E365 - E370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Rozance, S. W. Limesand, G. O. Zerbe, and W. W. Hay Jr. Chronic fetal hypoglycemia inhibits the later steps of stimulus-secretion coupling in pancreatic beta-cells Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1256 - E1264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Rozance, S. W. Limesand, and W. W. Hay Jr. Decreased nutrient-stimulated insulin secretion in chronically hypoglycemic late-gestation fetal sheep is due to an intrinsic islet defect Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E404 - E411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. W. Hay Jr Recent observations on the regulation of fetal metabolism by glucose J. Physiol., April 1, 2006; 572(1): 17 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. C. Mcmillen and J. S. Robinson Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming Physiol Rev, April 1, 2005; 85(2): 571 - 633. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
