Diacylglycerol production and protein kinase C activity are increased in a mouse model of diabetic embryopathy

Yuji Hiramatsu, Naotaka Sekiguchi, Michio Hayashi, Keiji Isshiki, Tamotsu Yokota, George L. King, Mary R. Loeken

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade by excess glucose has been implicated in vascular complications of diabetes. Its involvement in diabetic embryopathy has not been established. We examined DAG production and PKC activities in embryos and decidua of streptozotocin (STZ)-diabetic or transiently hyperglycemic mice during neural tube formation. STZ diabetes significantly increased DAG and total PKC activity in decidua (1.5- and 1.4-fold, respectively) and embryos (1.7- and 1.3-fold, respectively) on day 9.5. Membrane-associated PKC α, βII, δ, and ζ were increased in decidua by 1.25- to 2.8-fold. Maternal hyperglycemia induced by glucose injection on day 7.5, the day before the onset of neural tube formation, also increased DAG, PKC activity, and PKC isoforms (1.1-, 1.6-, and 1.5-fold, respectively) in the embryo on day 9.5. Notably, membrane-associated PKC activity was increased 24-fold in embryos of diabetic mice with structural defects. These data indicate that hyperglycemia just before organogenesis activates the DAG-PKC cascade and is correlated with congenital defects.

Original languageEnglish
Pages (from-to)2804-2810
Number of pages7
JournalDiabetes
Volume51
Issue number9
DOIs
Publication statusPublished - Sep 2002

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Hiramatsu, Y., Sekiguchi, N., Hayashi, M., Isshiki, K., Yokota, T., King, G. L., & Loeken, M. R. (2002). Diacylglycerol production and protein kinase C activity are increased in a mouse model of diabetic embryopathy. Diabetes, 51(9), 2804-2810. https://doi.org/10.2337/diabetes.51.9.2804