title: The kidney is resistant to chronic hypoglycaemia in late-gestation fetal sheep.
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.
authors.affiliation: Department of Physiology & Pharmacology, School of Medical Sciences, University of New South Wales, Sydney 2052, Australia. boyce@unsw.edu.au
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Boyce
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Gibson
authors.forename: E Marelyn
authors.initials: EM
authors.lastname: Wintour
authors.forename: Irene
authors.initials: I
authors.lastname: Koukoulas
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Gatford
authors.forename: Julie A
authors.initials: JA
authors.lastname: Owens
authors.forename: Eugenie R
authors.initials: ER
authors.lastname: Lumbers
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002245:Carbon Dioxide / Q000097:blood; D002908:Chronic Disease; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005865:Gestational Age; D006340:Heart Rate, Fetal / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000633:toxicity; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000633:toxicity; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D007677:Kidney Function Tests; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D011188:Potassium / Q000378:metabolism; D011247:Pregnancy; D012084:Renin-Angiotensin System / Q000187:drug effects; D012756:Sheep; D013002:Somatomedins / Q000378:metabolism