Comparison of alterations in insulin signalling pathway in adipocytes from Type II diabetic pregnant women and women with gestational diabetes mellitus

• Published in: Diabetologia 2002-04, Vol.45 (4), p.502-508
• Main Authors: TOMAZIC, M, JANEZ, A, SKETELJ, A, KOCIJANCIC, A, ECKEL, J, SHARMA, P. M
• Format: Article
• Language: English
• Subjects: Adipocytes - physiology; Adult; Biological and medical sciences; Cesarean Section; Diabetes Mellitus, Type 2 - physiopathology; Diabetes, Gestational - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Insulin - physiology; Insulin Receptor Substrate Proteins; Medical sciences; Phosphoproteins - metabolism; Phosphorylation; Phosphotyrosine - metabolism; Pregnancy; Pregnancy in Diabetics - physiopathology; Receptor, Insulin - metabolism; Signal Transduction - physiology
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-002-0791-z

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. 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. 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. 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.