TY - JOUR
T1 - Human umbilical cord blood-derived mesenchymal stem cells improve glucose homeostasis in rats with liver cirrhosis
AU - Jung, Kyung Hee
AU - Uhm, Yun Kyung
AU - Lim, Yun Jeong
AU - Yim, Sung Vin
PY - 2011/7
Y1 - 2011/7
N2 - Disturbance of glucose metabolism is a common feature in liver cirrhosis which is associated with insulin resistance and is an established risk factor for disease progression and survival in patients with chronic liver diseases. We investigated whether umbilical cord blood-derived mesenchymal stem cells (HMSCs) have an effect on the expression of molecules responsible for glucose utilization and hepatic gluconeogenesis, focusing on the insulin signaling pathway in rats with liver cirrhosis. Rats received a dose of CCl4 (100 μl/100 g 4:1 in corn oil) thrice-weekly HMSCs were infused at 4 weeks after induction of liver cirrhosis by CCl4. Infusion of HMSCs improved insulin resistance which was associated with increased glucose levels and decreased insulin sensitivity in CCl4-induced cirrhotic rats. HMSCs increased activities in the proximal part of the insulin signaling cascade, as evidenced by increased expression of key enzymes such as phosphatidylinositol-3-kinase (PI 3-kinase), protein kinase B (PKB), protein kinase C-ζ (PKC-ω), and the decrease of glycogen synthase kinase 3 (GSK-3) compared to CCl4-induced liver cirrhotic rats. We also observed that glucose-6-phosphatase (G-6-P) and phosphoenolpyruvate kinase (PEPCK), two hepatic enzymes involved in gluconeogenesis were strongly decreased over 40-50% after infusion of HMSCs. Taken together, our results showed that HMSCs could improve insulin resistance in CCl4-induced liver cirrhosis, thereby contributing to glucose homeostasis.
AB - Disturbance of glucose metabolism is a common feature in liver cirrhosis which is associated with insulin resistance and is an established risk factor for disease progression and survival in patients with chronic liver diseases. We investigated whether umbilical cord blood-derived mesenchymal stem cells (HMSCs) have an effect on the expression of molecules responsible for glucose utilization and hepatic gluconeogenesis, focusing on the insulin signaling pathway in rats with liver cirrhosis. Rats received a dose of CCl4 (100 μl/100 g 4:1 in corn oil) thrice-weekly HMSCs were infused at 4 weeks after induction of liver cirrhosis by CCl4. Infusion of HMSCs improved insulin resistance which was associated with increased glucose levels and decreased insulin sensitivity in CCl4-induced cirrhotic rats. HMSCs increased activities in the proximal part of the insulin signaling cascade, as evidenced by increased expression of key enzymes such as phosphatidylinositol-3-kinase (PI 3-kinase), protein kinase B (PKB), protein kinase C-ζ (PKC-ω), and the decrease of glycogen synthase kinase 3 (GSK-3) compared to CCl4-induced liver cirrhotic rats. We also observed that glucose-6-phosphatase (G-6-P) and phosphoenolpyruvate kinase (PEPCK), two hepatic enzymes involved in gluconeogenesis were strongly decreased over 40-50% after infusion of HMSCs. Taken together, our results showed that HMSCs could improve insulin resistance in CCl4-induced liver cirrhosis, thereby contributing to glucose homeostasis.
KW - Glucose-6-phosphatase
KW - Glycogen synthase kinase 3
KW - Insulin resistance
KW - Mesenchymal stem cell
KW - Phosphatidylinositol-3-kinase
KW - Umbilical cord bloods
UR - http://www.scopus.com/inward/record.url?scp=79956018039&partnerID=8YFLogxK
U2 - 10.3892/ijo.2011.1016
DO - 10.3892/ijo.2011.1016
M3 - Article
C2 - 21537835
AN - SCOPUS:79956018039
SN - 1019-6439
VL - 39
SP - 137
EP - 143
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 1
ER -