Summary
The relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor (InsR) and insulin resistance (IR) in patients with gestational diabetes mellitus (GDM) was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal non-pregnant women (normal non-pregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG (5.61±0.78 mmol/L), FINS (15.42±5.13 mU/L) and Homeostasis model assessment-IR (HOMA-IR) (1.21±0.52) in GDM group were significantly higher than those in normal pregnancy group (4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively) (P<0.01). The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal non-pregnant group (7.56±2.31 mU/L and 0.47±0.26 respectively) (P<0.01). There was no significant difference in the InsR expression level among the three groups (P>0.05). TP of InsR with insulin stimulation was significantly decreased in GDM group (0.20±0.05) as compared with normal pregnancy group (0.26±0.06) (P<0.01). TP of InsR with insulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group (0.31±0.06) (P<0.01). TP of InsR with insulin stimulation was negatively related with HOMA-IR in GDM group (r=−0.525, P<0.01). There was no correlation between the protein expression of InsR and HOMA-IR in GDM group (r=−0.236, P>0.05). It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.
Similar content being viewed by others
References
Agardh CD, Aberg A, Norden NE. Glucose levels and insulin secretion during a 75 g glucose challenge test in normal pregnancy. J Intern Med, 1996, 240(5):303–309
Stanley K, Fraser R, Bruce C. Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulin aemic euglycaemic clamp technique. Br J Obstet Gynecol, 1998, 105(7):756–757
Lee YH, White MF. Insulin receptor substrate proteins and diabetes. Arch Pharm Res, 2004, 27(4):361–370
Maegawa H. Impairments of insulin receptor function in insulin resistant states. Nippon Rinsho, 2000, 58(2): 304–309
Le J. Obstetrics & Gynecology. 7th eds. Beijing: People’s Medical Publishing House, 2007:150–154
Friedman JE, Ishizuka T, Shao J, et al. Impaired glucose transport and insulin receptor tyrosine phosphorylation in skeletal muscle from obese women with gestational diabetes. Diabetes, 1999, 48(9):1807–1814
Catalano PM, Drago NM, Amini SB. Longitudinal changes in pancreatic beta7 cell function and metabolic clearance rate of insulin in pregnant women with normal and abnormal glucose tolerance. Diabetes Care, 1998, 21(3):403–408
Catalano PM, Huston L, Amini SB, et al. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol, 1999, 180(4):903–916
Zimmer DM, Golichowsk AM, Karn CA, et al. Glucose and amino acid turnover in untreated gestational diabetes. Diabetes Care, 1996, 19(6):591–596
Akbay E, Tiras MB, Yetkin I, et al. Insulin secretion and insulin sensitivity in normal pregnancy and gestational diabetes mellitus. Gynecol Endocrinol, 2003, 17(2): 137–142
Sivan E, Homko CJ, Whittaker PG, et al. Free fatty acids and insulin resistance during pregnancy. J Clin Endocrinol Metab, 1998, 83(7):2338–2342
Saad MJ, Maeda L, Brenelli SL, et al. Defects in insulin signal transduction in liver and muscle of pregnant rats. Diabetologia, 1997, 40(2):179–186
Shao J, Catalano PM, Yamashita H, et al. Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoproteirrl overexpression in skeletal muscle from obese women with gestational diabetes mellitus (GDM): evidence for increased serine/threonine phosphorylation in pregnancy and GDM. Diabetes, 2000, 49(4): 603–610
Yamashita H, Shao J, Friedman JE. Physiologic and molecular alterations in carbohydrate metabolism during pregnancy and gestational diabetes mellitus. Clin Obstet Gynecol, 2000, 43(1):87–98
Kido Y, Burks DJ, Withers D, et al. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J Clin Invest, 2000, 105(2):199–205
Michael MD, Kulkarni RN, Postic C, et al. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell, 2000, 6(1):87–97
Elchebly M, Payette P, Michaliszyn E, et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science, 1999, 283(5407):l544–1548
Maddux BA, Goldfine ID. Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit. Diabetes, 2000, 49(1):13–19
May Y, Toth B, Keeton AB, et al. Mechanisms of hemorrhage-induced hepatic insulin resistance: role of tumor necrosis factor-α. Endocrinology, 2004, 145(11): 5168–5176.
Author information
Authors and Affiliations
Corresponding author
Additional information
The authors contributed equally to this work.
This project was supported by the Doctoral Fund of Shandong Province in China (No. 2006BS03053).
Rights and permissions
About this article
Cite this article
Chu, Yl., Gong, Yd., Su, Zh. et al. Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 393–397 (2014). https://doi.org/10.1007/s11596-014-1289-x
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-014-1289-x