M Tomazic1, A Janez, A Sketelj, A Kocijancic, J Eckel, P M Sharma. 1. Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloska 7, 1525 Ljubljana, Slovenia. marjeta.tomazic@kclj.si
Abstract
AIMS/HYPOTHESIS: The cellular mechanisms for the insulin resistance in pregnancy and gestational diabetes mellitus are not known. The membrane protein plasma cell glycoprotein PC-1 has been identified as an inhibitor of insulin receptor tyrosine kinase activity and could have a role in insulin resistance. This study aimed to examine the effects of insulin on glucose transport and changes in insulin receptor tyrosine phosphorylation, IRS-1 and PC-1. METHODS: Adipocytes were obtained either during elective cesarean section from three groups of subjects (Type II diabetic pregnant women ( n=6) women with gestational diabetes mellitus ( n=10) and pregnant women with normal glucose tolerance ( n=6) as pregnant control subjects) or during elective gynaecological surgery from non-pregnant ( n=6) control subjects. RESULTS: Insulin stimulated glucose transport was reduced by 50% in women with gestational diabetes mellitus and 70% in pregnant women with Type II diabetes, compared to the non-pregnant control subjects. After maximal insulin stimulation of adipocytes, IRTK phosphorylation was reduced by 29.5% in women with gestational diabetes mellitus and 44.5% in women with Type II diabetes, compared to the non-pregnant control subjects. We also found that IRS-1 phosphorylation was reduced by 32% and 48%, respectively. On the other hand, PC-1 content in adipocytes in women with gestational diabetes mellitus increased by 320% and 668% in Type II diabetic women, compared to the non-pregnant control subjects. CONCLUSIONS/ INTERPRETATION: Our results indicate that women with gestational diabetes mellitus and Type II diabetes have increased PC-1 content and suggest that this could contribute to lower phosphorylation levels of IRTK and IRS-1. Furthermore, these postreceptor defects in insulin signalling pathway are greater in both groups compared to the women with normal pregnancy. However, results from women with Type II diabetes show that pre-existing insulin resistance lead to an even greater deterioration of the signalling pathway.
AIMS/HYPOTHESIS: The cellular mechanisms for the insulin resistance in pregnancy and gestational diabetes mellitus are not known. The membrane protein plasma cell glycoprotein PC-1 has been identified as an inhibitor of insulin receptortyrosine kinase activity and could have a role in insulin resistance. This study aimed to examine the effects of insulin on glucose transport and changes in insulin receptortyrosine phosphorylation, IRS-1 and PC-1. METHODS: Adipocytes were obtained either during elective cesarean section from three groups of subjects (Type II diabetic pregnant women ( n=6) women with gestational diabetes mellitus ( n=10) and pregnant women with normal glucose tolerance ( n=6) as pregnant control subjects) or during elective gynaecological surgery from non-pregnant ( n=6) control subjects. RESULTS:Insulin stimulated glucose transport was reduced by 50% in women with gestational diabetes mellitus and 70% in pregnant women with Type II diabetes, compared to the non-pregnant control subjects. After maximal insulin stimulation of adipocytes, IRTK phosphorylation was reduced by 29.5% in women with gestational diabetes mellitus and 44.5% in women with Type II diabetes, compared to the non-pregnant control subjects. We also found that IRS-1 phosphorylation was reduced by 32% and 48%, respectively. On the other hand, PC-1 content in adipocytes in women with gestational diabetes mellitus increased by 320% and 668% in Type II diabeticwomen, compared to the non-pregnant control subjects. CONCLUSIONS/ INTERPRETATION: Our results indicate that women with gestational diabetes mellitus and Type II diabetes have increased PC-1 content and suggest that this could contribute to lower phosphorylation levels of IRTK and IRS-1. Furthermore, these postreceptor defects in insulin signalling pathway are greater in both groups compared to the women with normal pregnancy. However, results from women with Type II diabetes show that pre-existing insulin resistance lead to an even greater deterioration of the signalling pathway.