Oxygen consumption and guanosine diphosphate binding by fetal brown adipose tissue in diabetic pregnancy.
Oxygen consumption and 3H-guanosine diphosphate (GDP) binding were determined in brown adipocytes and mitochondria from 28-day gestation fetuses of alloxan-diabetic rabbit does and saline-injected controls. Maternal diabetes was classified as severe or mild determined by whether maternal blood glucose values were greater or less than 200 mg/dL, respectively, at death. Basal oxygen consumption and adipocyte diameters did not vary among groups. A significant reduction in maximal norepinephrine (NE) stimulated O2 consumption by fetal brown adipose tissue (BAT) cells was seen in offspring of severely diabetic pregnancies when compared with control values (248 +/- 53 +/- v482 +/- 32 microL O2/10(6) cells/h; P less than .005). In contrast, a significant increase in maximal NE-stimulated O2 consumption by fetal BAT cells occurred in offspring of mild diabetic pregnancies (807 +/- 60, P less than .001 v controls). A highly significant inverse correlation between serum glucose levels and maximal O2 consumption by fetal BAT was observed in fetuses from mild and severe diabetic pregnancies (r = -.98, P less than .005), and there was no correlation between these two parameters in offspring of normal pregnancies. A significant inverse correlation was observed between maximal O2 consumption by fetal BAT cells and serum insulin levels in offspring of both control and diabetic pregnancy (r = -.74; P less than .02). Tissue cytochrome oxidase activity was lower in offspring of severely affected diabetic does, indicating a reduction in BAT mitochondrial content compared with controls. BAT mitochondria from fetuses of severely diabetic does exhibited reduced 3H-GDP capacity, which was 2.5-fold lower than controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Neufeld
N D
ND
Division of Endocrinology, Ahmanson Pediatric Center, Cedar-Sinai Medical Center, UCLA School of Medicine 90048.
Corbo
L
L
Stoddard
A
A
Klein
A H
AH
Tadokoro
N
N
D002001:Adipose Tissue, Brown / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001833:Body Temperature Regulation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006150:Guanine Nucleotides / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D011817:Rabbits; D014280:Triglycerides / Q000032:analysis
D001786:Blood Glucose; D006150:Guanine Nucleotides; D007328:Insulin; D014280:Triglycerides; D006153:Guanosine Diphosphate; D003576:Electron Transport Complex IV