The kidney is resistant to chronic hypoglycaemia in late-gestation fetal sheep

Amanda Boyce, Karen J Gibson, Marelyn Wintour-Coghlan, Irene Koukoulas, Kathryn Gatford, Julie A Owens, Eugenie R Lumbers

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Abstract

We imposed a sustained reduction in glucose supply to late-gestation fetal sheep to see whether the reduction in glucose and insulin levels affected renal growth, renin expression and synthesis, and renal function. Maternal glucose concentrations were lowered to 1.7-1.9 mmol/L for 12-13 days by i.v. insulin infusion (n = 9, 121 days gestation, term = 150 days). Control ewes (n = 7) received vehicle. Maternal and fetal glucose concentrations were 40 and 31 lower than in controls (p <0.001), respectively. Fetal plasma insulin levels fell 36 +/- 7 by day 7 (p <0.05); IGF-I levels were unchanged. Arterial PO2 and pH increased and PCO2 fell (p <0.05). Renal function was largely unaffected. Longitudinal growth was 28 slower and spleen weights were 36 smaller (p <0.05); body and kidney weights were not affected. Renal renin levels and renin, angiotensinogen, and angiotensin receptor mRNA levels were similar to those of controls. Plasma renin levels increased from 2.1 +/- 0.6 to 7.6 +/- 2.8 ng angiotensin I.mL-1.h-1 (p = 0.01). Thus reductions in fetal glucose and insulin levels in late gestation that were sufficient to retard skeletal growth had no effect on kidney growth or function or the renal renin-angiotensin system, possibly because IGF-I levels were not reduced. There was, however, increased activity of the circulating renin-angiotensin system similar to that seen during insulin-induced hypoglycaemia.
Original languageEnglish
Pages (from-to)597 - 605
Number of pages9
JournalCanadian Journal of Physiology and Pharmacology
Volume85
Issue number6
Publication statusPublished - 2007

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