Extrapancreatic roles of glimepiride on osteoblasts from rat manibular bone in vitro: Regulation of cytodifferentiation through PI3-kinases/Akt signalling pathway.
Glimepiride, a third-generation sulfonylurea, has also been reported to have extrapancreatic functions including activation of PI3-kinase (PI3K) and Akt in rat adipocytes, skeletal muscle and endothelial cells. It is tempting to speculate that glimepiride would improve bone-implant contact in diabetic patients by mediating the activity of GLUT1 and 3 via the PI3K/Akt pathway. In this study, we investigated the effects of glimepiride on rat mandible osteoblasts cultured under two different levels of glucose. Cell proliferation was determined by the MTT assay. The supernatant was used to measure alkaline phosphatase (ALP) activity. Glucose uptake was determined by measuring the rate of 2-deoxy-d-glucose (2-DG) uptake. Western blotting was performed used to determine collagen I and PI3K/Akt expression. RT-PCR was performed used to determine osteocalcin (OCN) mRNA expression. We found that hyperglycemia down-regulated proliferation, ALP activity, OCN mRNA and GLUT3 protein expression in rat osteoblasts, and upregulated collagen I and GLUT1 protein expressions. Glimepiride enhanced the proliferation, ALP activity and OCN mRNA levels, and upregulated collagen I and GLUT1 and 3 protein expressions of rat osteoblasts at two different glucose concentrations. This study also provides the first evidence that glimepiride stimulates the phosphorylation of PI3K/Akt in osteoblasts and ameliorated the damage caused by high concentrations of glucose through the PI3K/Akt pathway.
Institute of Stomatology, Chinese General Hospital of the PLA, 28 Fuxing Road, Haidian District, Beijing 100853, PR China.
Pan
P
Ma
Wei
W
Xiong
Hongchen
H
Liu
Junli
J
Ma
Bin
B
Gu
Xia
X
Wu
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020536:Enzyme Activators / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage; D051272:Glucose Transporter Type 1 / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008334:Mandible / Q000166:cytology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015675:Osteocalcin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D024042:Collagen Type I; D020536:Enzyme Activators; D051272:Glucose Transporter Type 1; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D013453:Sulfonylurea Compounds; D015675:Osteocalcin; C057619:glimepiride; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000469:Alkaline Phosphatase; D005947:Glucose