title: Human umbilical cord blood-derived mesenchymal stem cells improve glucose homeostasis in rats with liver cirrhosis.
abstract: 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-ζ), 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Jung
authors.forename: Yun-Kyung
authors.initials: YK
authors.lastname: Uhm
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Lim
authors.forename: Sung-Vin
authors.initials: SV
authors.lastname: Yim
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002725:Chloroform / Q000009:adverse effects; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology*; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D002725:Chloroform; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose