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Attenuated insulin release and storage in fetal sheep pancreatic islets with intrauterine growth restriction.
Endocrinology 2006; 147(3):1488-97E

Abstract

We determined in vivo and in vitro pancreatic islet insulin secretion and glucose metabolism in fetuses with intrauterine growth restriction (IUGR) caused by chronic placental insufficiency to identify functional deficits in the fetal pancreas that might be caused by nutrient restriction. Plasma insulin concentrations in the IUGR fetuses were 69% lower at baseline and 76% lower after glucose-stimulated insulin secretion (GSIS). Similar deficits were observed with arginine-stimulated insulin secretion. Fetal islets, immunopositive for insulin and glucagon, secreted insulin in response to increasing glucose and KCl concentrations. Insulin release as a fraction of total insulin content was greater in glucose-stimulated IUGR islets, but the mass of insulin released per IUGR islet was lower because of their 82% lower insulin content. A deficiency in islet glucose metabolism was found in the rate of islet glucose oxidation at maximal stimulatory glucose concentrations (11 mmol/liter). Thus, pancreatic islets from nutritionally deprived IUGR fetuses caused by chronic placental insufficiency have impaired insulin secretion caused by reduced glucose-stimulated glucose oxidation rates, insulin biosynthesis, and insulin content. This impaired GSIS occurs despite an increased fractional rate of insulin release that results from a greater proportion of releasable insulin as a result of lower insulin stores. Because this animal model recapitulates the human pathology of chronic placental insufficiency and IUGR, the beta-cell GSIS dysfunction in this model might indicate mechanisms that are developmentally adaptive for fetal survival but in later life might predispose offspring to adult-onset diabetes that has been previously associated with IUGR.

Authors+Show Affiliations

Department of Animal Sciences, University of Arizona, P.O. Box 210035, Tucson, Arizona 85721-0035, USA. Limesand@ag.arizona.edu

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16339204

Citation

Limesand, Sean W., et al. "Attenuated Insulin Release and Storage in Fetal Sheep Pancreatic Islets With Intrauterine Growth Restriction." Endocrinology, vol. 147, no. 3, 2006, pp. 1488-97.
Limesand SW, Rozance PJ, Zerbe GO, et al. Attenuated insulin release and storage in fetal sheep pancreatic islets with intrauterine growth restriction. Endocrinology. 2006;147(3):1488-97.
Limesand, S. W., Rozance, P. J., Zerbe, G. O., Hutton, J. C., & Hay, W. W. (2006). Attenuated insulin release and storage in fetal sheep pancreatic islets with intrauterine growth restriction. Endocrinology, 147(3), pp. 1488-97.
Limesand SW, et al. Attenuated Insulin Release and Storage in Fetal Sheep Pancreatic Islets With Intrauterine Growth Restriction. Endocrinology. 2006;147(3):1488-97. PubMed PMID: 16339204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuated insulin release and storage in fetal sheep pancreatic islets with intrauterine growth restriction. AU - Limesand,Sean W, AU - Rozance,Paul J, AU - Zerbe,Gary O, AU - Hutton,John C, AU - Hay,William W,Jr Y1 - 2005/12/08/ PY - 2005/12/13/pubmed PY - 2006/4/14/medline PY - 2005/12/13/entrez SP - 1488 EP - 97 JF - Endocrinology JO - Endocrinology VL - 147 IS - 3 N2 - We determined in vivo and in vitro pancreatic islet insulin secretion and glucose metabolism in fetuses with intrauterine growth restriction (IUGR) caused by chronic placental insufficiency to identify functional deficits in the fetal pancreas that might be caused by nutrient restriction. Plasma insulin concentrations in the IUGR fetuses were 69% lower at baseline and 76% lower after glucose-stimulated insulin secretion (GSIS). Similar deficits were observed with arginine-stimulated insulin secretion. Fetal islets, immunopositive for insulin and glucagon, secreted insulin in response to increasing glucose and KCl concentrations. Insulin release as a fraction of total insulin content was greater in glucose-stimulated IUGR islets, but the mass of insulin released per IUGR islet was lower because of their 82% lower insulin content. A deficiency in islet glucose metabolism was found in the rate of islet glucose oxidation at maximal stimulatory glucose concentrations (11 mmol/liter). Thus, pancreatic islets from nutritionally deprived IUGR fetuses caused by chronic placental insufficiency have impaired insulin secretion caused by reduced glucose-stimulated glucose oxidation rates, insulin biosynthesis, and insulin content. This impaired GSIS occurs despite an increased fractional rate of insulin release that results from a greater proportion of releasable insulin as a result of lower insulin stores. Because this animal model recapitulates the human pathology of chronic placental insufficiency and IUGR, the beta-cell GSIS dysfunction in this model might indicate mechanisms that are developmentally adaptive for fetal survival but in later life might predispose offspring to adult-onset diabetes that has been previously associated with IUGR. SN - 0013-7227 UR - https://www.unboundmedicine.com/medline/citation/16339204/Attenuated_insulin_release_and_storage_in_fetal_sheep_pancreatic_islets_with_intrauterine_growth_restriction_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2005-0900 DB - PRIME DP - Unbound Medicine ER -