Blood Glucose of Mother and Fetus during Late Pregnancy of Rats with a Glycogen Storage Disorder

Abstract

The gsd/gsd rat is unable to mobilize liver glycogen due to an absence of phosphorylase b kinase activity. Unlike the normal rat, the maternal gsd/gsd rat cannot maintain its blood glucose concentration in late pregnancy, and values of 3.25 ± 0.22 mM were found just before birth. The blood glucose of the gsd/gsd fetus falls to 1.76 ± 0.09 raMat day 19 of gestation and does not rise appreciably again before birth. In contrast, normal fetal rats show a steady rise in blood glucose from hypoglycemic levels at day 19 to a value of 5.70 ± 0.12 mM on the day of birth. These results indicate that the normal fetal rat contributes towards the regulation of its own blood glucose in late gestation by utilizing its liver glycogen stores.

Relationship between Liver Glycogen Metabolism and Glucose Homeostasis in the Fetal Rat: Studies with the <i>gsd/gsd</i> Rat

“…The observations with gsd/gsd and normal fetuses also argue in favour of there being glycogenolysis in the liver of the normal rat fetus, since in the absence of this mechanism, the fetal rat be comes hypoglycemic in utero [4], These ob servations point to the physiological impor tance of this mechanism, whereby the fetus is able to contribute to its own blood glucose pool through mobilisation of its liver gly cogen reserves and to the significance of the high 'basal' phosphorylase activities reported over this period of glycogenesis in the fetal rat [2,6,7], The phosphorylase b kinase defi ciency in the gsd/gsd rat is an autosomal recessive trait, and nonpregnant heterozy gous animals appear to be normal in all respects [5]. In pregnancy, however, there is a tendency for the maternal blood glucose con centration to be intermediate between that seen in control and in homozygous mothers (see results).…”

“…phorylase b kinase, and hence unable to mo bilise liver glycogen (gsd/gsd) [5], we have shown that the maternal blood glucose con centration is reduced compared with normal animals, and that the fetal blood glucose con centration does not rise before birth, remain ing around 2 mmol/1 from 19 days to term [4], Despite these apparent restrictions on glucose supply, the fetal gsd/gsd rats lay down more glycogen in the liver than normal fetuses [4], We have previously postulated that fetal liver glycogen deposition in the nor mal animal is regulated by the ratio of active glycogen phosphorylase (a) to active glycogen synthase (a) [6], a concept which has been supported by others [7,8]. The observations with gsd/gsd and normal fetuses also argue in favour of there being glycogenolysis in the liver of the normal rat fetus, since in the absence of this mechanism, the fetal rat be comes hypoglycemic in utero [4], These ob servations point to the physiological impor tance of this mechanism, whereby the fetus is able to contribute to its own blood glucose pool through mobilisation of its liver gly cogen reserves and to the significance of the high 'basal' phosphorylase activities reported over this period of glycogenesis in the fetal rat [2,6,7], The phosphorylase b kinase defi ciency in the gsd/gsd rat is an autosomal recessive trait, and nonpregnant heterozy gous animals appear to be normal in all respects [5].…”

“…This glycogen deposition is accompanied by a steady rise in blood glu cose concentration, so that by term, the fetal/maternal glucose gradient is almost lost [4], In a strain of rats deficient in liver phos- 1 Supported by a grant of the Medical Research Council of New Zealand.…”

Prenatal expression of a lethal genetic defect in carbohydrate metabolism in mice.

“…While in utero, cab/cab fetuses are spontaneously active and responsive to mechanical stimulation. However, [3][4][5] min after separation from the mother by cesarean section, there is loss of all spontaneous and induced movements in affected homozygotes. The mutants show no gross anomalies and are morphologically indistinguishable from normal littermates.…”

“…There exist several hereditary disorders which result in the reduction of prenatal glycogen storage in humans, such as glycogen synthase deficiencies (3). Genetic defects are also known to prevent the postnatal breakdown of glycogen in humans and experimental animals (3)(4)(5). Yet, neither of these two classes of disorders causes death within minutes of parturition.…”