Effects of Brief Exposure to Insulin-Induced Hypoglycemic Serum During Organogenesis in Rat Embryo Culture

Akazawa, M.; Akazawa, Shoichi; Hashimoto, Masumi; Akashi, M; Yamazaki, Hironori; Tahara, Daigo; Yamamoto, H.; Yamaguchi, Yoshihiko; Nakanishi, Tomohiro; Nagataki, Shigenobu

doi:10.2337/diab.38.12.1573

Cited by 31 publications

(9 citation statements)

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“…Indeed, during early stages of organogenesis, the neural tube and heart are particularly sensitive to teratogens. Hypoglycemia, for example, has been shown to be dysmorphogenic in rodent embryos exposed in vivo (Buchanan et al 1986;Ellington 1980) or in vitro (Ellington 1980Sadler and Hunter 1987;Akazawa et al 1987;Akazawa 1989;Smoak and Sadler 1990). Defects following hypoglycemic exposures in early post-implantation mouse embryos commonly affected the heart and neural tube (Buchanan et al 1986;Sadler and Hunter 1987;Smoak and Sadler 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Hypoglycemia, which is the classic inducer of GRP synthesis, has been shown to cause dysmorphogenesis in rodent embryos in vivo (Buchanan et al 1986;Ellington 1980) and in vitro (Ellington 1980;Sadler and Hunter 1987;Smoak and Sadler 1990;Akazawa et al 1987;Akazawa et al 1989), with defects commonly affecting the heart (Buchanan et al 1986;Sadler and Hunter 1987;Smoak and Sadler 1990). Thus, GRPs may play a role in hypoglycemia-induced cardiac defects.…”

Section: Introductionmentioning

confidence: 99%

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Immunolocalization and heart levels of GRP94 in the mouse during post-implantation development

Barnes¹,

Smoak²

1997

Anatomy and Embryology

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Glucose-regulated proteins (GRPs), which belong to the highly conserved family of stress proteins, are resident to the endoplasmic reticulum and function as molecular chaperones. Heat shock proteins have been shown to be developmentally regulated, but little work has been done to investigate the expression of GRPs during embryogenesis. Therefore, this study examined the distribution of GRP94 within mouse embryos during the period of organogenesis and characterized levels of GRP94 within the developing heart during organogenesis and late fetal stages. Our results demonstrate that the GRP94 protein is constitutively expressed within mouse embryos during early stages of organogenesis and is localized particularly within the developing heart, neuroepithelium, and surface ectoderm tissues. Positive staining for GRP94 remains within developing heart tissues throughout organogenesis and is found primarily within the atrial and ventricular myocardial cells. Western blot analysis of GRP94 expression demonstrates a significantly higher level of GRP94 in embryonic hearts during early stages of organogenesis than in later stages of organogenesis or the fetal period. These results demonstrate that the stress protein GRP94 is constitutively expressed within specific tissues during post-implantation mouse development and suggest that GRPs may play an important role in the process of myocardial cell differentiation and heart development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunolocalization and heart levels of GRP94 in the mouse during post-implantation development

Barnes¹,

Smoak²

1997

Anatomy and Embryology

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“…Recent work with rats has shown that hypoglycaemia at a critical stage of development-namely, equivalent to days 32-40 in humans (18)(19)(20)(21)(22)(23)(24)(25)(26) days after ovulation)-can cause congenital abnormalities.1316 Hence the desirability of reducing blood glucose concentrations in early pregnancy has been questioned. 16 This paper reports the first 14 years' experience of our prepregnancy clinic, comparing results in women who attended the clinic with those in a group of women who did not.…”

Section: Introductionmentioning

confidence: 99%

Can prepregnancy care of diabetic women reduce the risk of abnormal babies?

Steel

Johnstone²,

Hepburn³

et al. 1990

BMJ

185

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controlled for in the multivariate analvsis. Furthermore, the suggested risk factors occurring later in life, such as psychological mechanisms and drug availability and exposition, cannot explain the demonstrated associations between administration of drugs during the perinatal period and subsequent addiction in offspring. Also, genetic and socioeconomic factors were largely controlled for by matching addicts with their own siblings.In conclusion, effective pain relief is sometimes an important factor for a successful outcome of delivery, as well as for the ability of the mother to accept and care for the child in the future. At present, when considering the choice of analgesic method immediate risks and benefits are mainly taken into account. When depressant or sedative drugs are used their possible long term effects due to imprinting also seem to be important. From this point of view, analgesic methods not associated with passage of substantial amounts of drugs across the placenta are preferable. Our Abstract Objective-To see whether a prepregnancy clinic for diabetic women can achieve tight glycaemic control in early pregnancy and so reduce the high incidence of major congenital malformation that occurs in the infants of these women. Design-An analysis of diabetic control in early pregnancy including a record of severe hypoglycaemic episodes in relation to the occurrence of major congenital malformation among the infants.Setting-A diabetic clinic and a combined diabetic and antenatal clinic of a teaching hospital.Patients -143 Insulin dependent women attending a prepregnancy clinic and 96 insulin dependent women managed over the same period who had not received specific prepregnancy care.Main outcome measure-The incidence of major congenital malformation.Results-Compared with the women who were not given specific prepregnancy care the group who attended the prepregnancy clinic had a lower haemoglobin Al concentration in the first trimester (8.4% v 10-5%), a higher incidence of hypoglycaemia in early pregnancy (38/143 women v 8/96), and fewer infants with congenital abnormalities (2/143 v 10/96; relative risk among women not given specific prepregnancy care 7-4 (95% confidence interval 1-7 to 33.2)).Conclusion-Tight control of the maternal blood glucose concentration in the early weeks of pregnancy can be achieved by the prepregnancy clinic approach and is associated with a highly significant reduction in the risk of serious congenital abnormalities in the offspring. Hypoglycaemic episodes do not seem to lead to fetal malformation even when they occur during the period of organogenesis.

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“…The malformations usually occur before the 7th week of gestation and include central nervous system deformities and cardiac anomalies (Mills et al, 1979). The causes underlying the teratogenic process are not completely clear, although dysmorphogenesis in rodent embryo culture systems can be elicited by adding somatomedin inhibitors, and by raising or decreasing sucrose level in the bathing medium (Akazawa et al, 1987(Akazawa et al, , 1989Freinkel et al, 1986). A poor control of blood glucose levels during early pregnancy might increase the risk of malformations.…”

Section: Introductionmentioning

confidence: 99%

Progressive and selective changes in neurotrophic factor expression and substance p axonal transport induced by perinatal diabetes: Protective action of antioxidant treatment

Germani¹,

Lesma²,

Giulio³

et al. 1999

J. Neurosci. Res.

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Diabetes-induced embryo malformations and growth retardation are correlated with a variety of biochemical changes including oxidative stress. In this study, we show that the morphological alterations are correlated with progressive and selective changes of mRNA expression in specific neurotrophic factors. At embryological stage E-17, diabetes affected both embryo growth and NGF mRNA expression, which was reduced by as much as 90 and 56% in target tissues of sensory system such as tongue and intestine, respectively. The reduction in retina and heart was around 50%. Conversely, the mRNA expression of low-affinity neurotrophin receptor p75 was increased. At birth, BDNF mRNA expression was affected with a significant generalized reduction,while in vibrissae we observed a reduction of BDNF and p75 mRNAs and an increase of NGF. At postnatal day 14, pups from diabetic mothers showed reduced muscle levels of IGF-I, while we observed a partial impairment of substance P axonal transport at postnatal day 28. Treatment of diabetic mothers with silybin, a flavonoid with antioxidant properties, prevented most of the changes in neurotrophic factor expression and substance P axonal transport with no effects on hyperglycemia and embryo growth retardation. These results indicate that oxidative stress may influence neurotrophic factor synthesis in target territories during development. In addition, these data suggest that nervous system abnormalities observed in diabetic embryopathy may also derive by insufficient neurotrophic factor biosynthesis involving sequentially NGF in the embryo and BDNF and IGF-I in the early postnatal days. Insulin treatment of diabetic mothers normalized hyperglycemia and body growth, with consequent regular embryonic and postnatal development.

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Effects of Brief Exposure to Insulin-Induced Hypoglycemic Serum During Organogenesis in Rat Embryo Culture

Cited by 31 publications

References 0 publications

Immunolocalization and heart levels of GRP94 in the mouse during post-implantation development

Immunolocalization and heart levels of GRP94 in the mouse during post-implantation development

Can prepregnancy care of diabetic women reduce the risk of abnormal babies?

Progressive and selective changes in neurotrophic factor expression and substance p axonal transport induced by perinatal diabetes: Protective action of antioxidant treatment

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