AJP - Endo AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab (March 28, 2006). doi:10.1152/ajpendo.00643.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/2/E404    most recent
00643.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rozance, P. J.
Right arrow Articles by Hay, Jr., W. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rozance, P. J.
Right arrow Articles by Hay, Jr., W. W.
Submitted on December 21, 2005
Accepted on March 26, 2006

Decreased Nutrient Stimulated Insulin Secretion in Chronically Hypoglycemic Late Gestation Fetal Sheep is Due to an Intrinsic Islet Defect

Paul J. Rozance1*, Sean W. Limesand2, and William W. Hay, Jr.1

1 Perinatal Research Center, University of Colorado School of Medicine, Aurora, Colorado, United States
2 Animal Sciences, University of Arizona, Tucson, Arizona, United States

* To whom correspondence should be addressed. E-mail: paul.rozance{at}uchsc.edu.

Abstract We measured in vivo and in vitro nutrient stimulated insulin secretion in late gestation fetal sheep to determine if an intrinsic islet defect is responsible for decreased glucose stimulated insulin secretion (GSIS) in response to chronic hypoglycemia. Control fetuses responded to both leucine and lysine infusions with increased arterial plasma insulin concentrations (average increase: 0.13±0.05 ng/ml, leucine; 0.99±0.26 ng/ml lysine). In vivo lysine stimulated insulin secretion was decreased by chronic (0.37±0.18 ng/ml) and acute (0.27±0.19 ng/ml) hypoglycemia. Leucine did not stimulate insulin secretion following acute hypoglycemia but was preserved with chronic hypoglycemia (0.12±0.09 ng/ml). Isolated pancreatic islets from chronically hypoglycemic fetuses had normal insulin and DNA content but decreased fractional insulin release when stimulated with glucose, leucine, arginine, or lysine. Isolated islets from control fetuses responded to all nutrients. Therefore, chronic late gestation hypoglycemia causes defective in vitro nutrient regulated insulin secretion that is, at least partly, responsible for diminished in vivo GSIS. Chronic hypoglycemia is a feature of human intrauterine growth restriction and might lead to an islet defect that is responsible for the decreased insulin secretion patterns seen in human IUGR fetuses and low birth weight human infants.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
S. W. Limesand, P. J. Rozance, L. D. Brown, and W. W. Hay Jr.
Effects of chronic hypoglycemia and euglycemic correction on lysine metabolism in fetal sheep
Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E879 - E887.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
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]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2006 by the American Physiological Society.