Adaptation of ovine fetal pancreatic insulin secretion to chronic hypoglycaemia and euglycaemic correction

Sean W. Limesand, William W. Hay

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51 Scopus citations


Fetal pancreatic adaptations to relative hypoglycaemia, a characteristic of intra-uterine growth restriction, may limit pancreatic β-cell capacity to produce and/or secrete insulin. The objective of this study was to measure β-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 β-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.

Original languageEnglish (US)
Pages (from-to)95-105
Number of pages11
JournalJournal of Physiology
Issue number1
StatePublished - Feb 15 2003

ASJC Scopus subject areas

  • Physiology


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