Prolonged exposure to insulin with insufficient glucose leads to impaired Glut4 translocation.
Insulin maintains glucose homeostasis by stimulating glucose uptake from extracellular environment to adipose and muscle tissue through glucose transporter (GLUT4). Insulin resistance plays a significant role in pathologies associated with type2 diabetes. It has been previously shown that hyperinsulinemia can lead to insulin resistance. In these studies very high levels of insulin was used to achieve insulin resistance. We hypothesized that one of the causes of type 2 diabetes could be insulin synthesis in the absence of glucose stimulation. We used CHO cell line, stably expressing Myc-GLUT4-GFP along with human insulin receptor to study the effect of hyperinsulinemia in the presence of low glucose (6.5 mM) or high glucose (20 mM). The insulin responsiveness of these cells was assessed by FRAP, FACS and subcellular fractionation. The results suggest that exposure of cells to insulin in low glucose conditions made these cells insulin resistant within 10 passages, while the same level of insulin in the presence of high glucose did not result in insulin resistance. These results clearly suggest that hyperinsulinemia combined with hypoglycaemia may lead to insulin resistance and may be one of the causes for the typ2 diabetes.
Biotechnology Department, Savitribai Phule Pune University, Pune 411007 India; National Centre for Cell Science, Pune 411007 India.
Abdul
A
Khalique
Biotechnology Department, Savitribai Phule Pune University, Pune 411007 India; National Centre for Cell Science, Pune 411007 India.
Rucha D
RD
Sarwade
Biotechnology Department, Savitribai Phule Pune University, Pune 411007 India; National Centre for Cell Science, Pune 411007 India.
Poonam R
PR
Pandey
National Centre for Cell Science, Pune 411007 India.
M V
MV
Vijayakumar
National Centre for Cell Science, Pune 411007 India.
Manoj K
MK
Bhat
National Centre for Cell Science, Pune 411007 India. Electronic address: seshadrv@yahoo.com.
Vasudevan
V
Seshadri
D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D005947:Glucose / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects*; D007333:Insulin Resistance; D021381:Protein Transport / Q000187:drug effects
D051275:Glucose Transporter Type 4; D007328:Insulin; C495692:SLC2A4 protein, human; D005947:Glucose
Diabetes; Glucose transporter (GLUT4); Insulin