Chronic Maternal Hyperinsulinemia and Hypoglycemia

Gruppuso, Philip A.; Migliori, Richard J.; Susa, John B.; Schwartz, Robert

doi:10.1159/000241479

Cited by 40 publications

(13 citation statements)

References 22 publications

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“…This apparent "overcompensation" could be due to reduced availability of other metabolic fuels. Our laboratory has shown diminished total amino acid plasma concentrations in pregnant rats and their fetuses after prolonged maternal insulin infusions (6), and others have found lower alanine concentrations (5). The reduction of these and other fuels may have increased the glucose demand by fetal brain.…”

Section: Discussionmentioning

confidence: 98%

“…To address the role of limited glucose availability without hypoxia and acidosis upon fetal tissue glucose utilization, we used another model of IUGR in which a continuous infusion of insulin produces maternal hypoglycemia (5). This technique limits glucose availability, resulting in fetal hypoglycemia and hypoinsulinemia, but does not alter placental gaseous exchange (6).…”

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confidence: 99%

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Differential Effects of Short and Long Durations of Insulin-Induced Maternal Hypoglycemia upon Fetal Rat Tissue Growth and Glucose Utilization

et al. 1992

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ABSTRACI'. We studied the effects of short and long durations of insulin-induced maternal hypoglycemia upon in vivo glucose utilization of several fetal tissues in the rat. Osmotic minipumps filled with insulin were implanted in pregnant rats on d 15 or 18 of gestation (term 21.5 d), and radiolabeled 2-deoxyglucose was used to measure relative glucose utilization rates (rCU) of fetal liver, lung, muscle, kidney, heart, placenta, and brain on d 20 of gestation after 2 or 5 d of hypoglycemia. Maternal plasma glucose concentrations decreased within 24 h of pump placement and remained less than controls throughout gestation. Fetal plasma glucose and insulin concentrations on d 20 were equally reduced after 2 and 5 d of hypoglycemia. Both 2 and 5 d of hypoglycemia were associated with significant reductions in the rCU of fetal liver, lung, and muscle. Reductions in fetal kidney rCU also occurred after 2 and 5 d of hypoglycemia but to a smaller degree. rGU of fetal heart was reduced after 2 d of hypoglycemia, but was normal after 5 d of hypoglycemia. Both 2 and 5 d of hypoglycemia were associated with increased rCU of fetal brain. Five d, but not 2 d of hypoglycemia resulted in decreased fetal weight on d 20 of gestation. However, at term, newborn pups delivered of hypoglycemic mothers weighed significantly less than controls regardless of the timing of minipump placement. Liver, lung, and carcass of these growth-retarded pups weighed less than control tissues, whereas kidney, heart, and brain weights were not affected. We speculate that fetal tissue growth and glucose utilization are influenced by common mechanisms and that glucose utilization may be an important determinant of fetal tissue growth. (Pediatr Res 32: 436-440, 1992) Abbreviations rCU, relative glucose utilization IUGR, intrauterine growth retardation 2DG, 2-deoxyglucose 2DG6P, 2-deoxyglucose-6-phosphate Pk, placental discrimination constant IUGR is a frequently occurring obstetrical problem associated with an increased incidence of perinatal mortality and morbidity. Limited metabolic fuel availability to the fetus is an important factor in the development of IUGR. Decreased availability of maternally derived glucose is responsible for diminished plasma glucose and insulin concentrations in growth-retarded human fetuses (l,2). Fetal hypoglycemia and hypoinsulinemia, in turn, are major factors retarding fetal growth; glucose is a primary fetal metabolic substrate and insulin is a key growth-stimulating hormone that has mitogenic and numerous anabolic effects.The effects of limited glucose availability upon fetal growth is apparently tissue-specific because IUGR often results in asymmetric fetal growth, i.e. limited somatic but normal brain growth. The mechanisms for this phenomenon are not completely understood. Whether glucose utilization of specific tissues reflects these differential growth patterns under conditions of limited glucose availability is not known and is the focus of this study.We previously studied the effects of maternal uterine arter...

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Differential Effects of Short and Long Durations of Insulin-Induced Maternal Hypoglycemia upon Fetal Rat Tissue Growth and Glucose Utilization

et al. 1992

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“…On day 20, control fetuses weighed 3.65 ± 0.37 g while experimental fetuses were 3.55 ± 0.35 g. On day 21, fetal weight was 4.26 ± 0.80 for con- trol animals and 4.20 ± 0.60 g for experi mental fetuses. When pooled with data from our previous study [15], minimal IUGR is present on day 21. For day 21, the values for the controls arc 4.59 ± 0.84 (n = 97) and 4.36 ± 0.66 (n = 88) for the experimentáis (p < 0.001 by two-way analysis of variance).…”

Section: Resultsmentioning

confidence: 77%

“…A competi tive protein-binding assay was used to measure total hepatic cyclic adenosine monophosphate (AMP) con centration [14], Data are expressed as mean ± 1 SD and analyzed by Student's unpaired t tests, except in the case of nonparamctric data where medians and ranges are given; the Mann-Whitney rank sum test was used for analy sis. Fetal weights from a previous study [15] were ana lyzed with the present data by means of two-way anal ysis of variance.…”

Section: Methodsmentioning

confidence: 99%

Induction in utero of Hepatic Glucose-6-Phosphatase by Fetal Hypoinsulinemia

Domenech¹,

Gruppuso²,

Susa³

et al. 1985

Neonatology

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The effect of fetal hypoglycemia and hypoinsulinemia on fetal rat hepatic glucose-6-phosphatase activity was studied. Fetal hypoglycemia and hypoinsulinemia were produced by inducing maternal hyperinsulinemia and hypoglycemia secondary to the exogenous administration of insulin via implantation of osmotically driven minipumps on day 15 of gestation into 15 experimental animals. 13 animals served as sham-operated controls. Cesarean sections were performed on day 20 or 21 of gestation under pentobarbital anesthesia. Liver glucose-6-phosphatase activity was increased in the hypoinsulinemic fetuses. In contrast, the hyperinsulinemic mothers had suppressed hepatic glucose-6-phosphatase activity. Hypoinsulinemia would appear to be the primary stimulus for enhanced fetal glucose-6-phosphatase in this model.

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“…Although several studies that have explored the relationship between exces sive fetal insulin release and fetal overgrowth in animals are available [2][3][4], the importance o f fetal endogenous insulin release for normal fetal growth regulation is unclear. Fetal hypoinsulinemia was induced in fetal rats [5] by induction o f chronic maternal hypoglycemia which caused a significant reduction in fetal growth. Fetal surgical [6] or chemical [7,8] pancreatectomy has also been variously relat ed to some reduction in fetal growth as well.…”

Section: Introductionmentioning

confidence: 99%

Effect of Hypoinsulinemia on Growth in the Fetal Rabbit

Chaffin¹,

Clark

Mccracken

et al. 1995

Neonatology

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Insulin is an important regulatory hormone in the control of fetal growth. In a fetal rabbit model, a non-ruminant species, the effects of insulin deprivation on glucose, growth and protein metabolism were studied. The fetuses of 10 pregnant New Zealand white rabbits in one uterine horn received a subcutaneous injection on day 25 of gestation (term = 30 days) of 0.1 mg streptozotocin (STZ)/gm fetal weight. The fetuses in the opposite horn received a sham injection of buffer. The dams were then killed on day 29. The fetal insulin concentration was depressed by 38%, and the serum glucose concentration was elevated by 28% in animals given STZ when compared to control animals. Fetal weights, carcass weights and skeletal growth, as measured by crown-rump length and tibial length of STZ-treated fetuses, were significantly reduced by 7–13%. However, organ weights were not significantly different, except for the kidneys which were 17% lighter. Protein and mineral contents of the carcasses were also reduced compared to the control fetuses. Thus, insulin deprivation in fetal rabbits results in significant growth impairment in a pattern similar to that of human asymmetric intrauterine growth retardation.

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Chronic Maternal Hyperinsulinemia and Hypoglycemia

Cited by 40 publications

References 22 publications

Differential Effects of Short and Long Durations of Insulin-Induced Maternal Hypoglycemia upon Fetal Rat Tissue Growth and Glucose Utilization

Differential Effects of Short and Long Durations of Insulin-Induced Maternal Hypoglycemia upon Fetal Rat Tissue Growth and Glucose Utilization

Induction in utero of Hepatic Glucose-6-Phosphatase by Fetal Hypoinsulinemia

Effect of Hypoinsulinemia on Growth in the Fetal Rabbit

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