PMID- 28413172 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20180326 IS - 1348-4540 (Electronic) IS - 0918-8959 (Linking) VI - 64 IP - 5 DP - 2017 May 30 TI - The effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats. PG - 543-552 LID - 10.1507/endocrj.EJ16-0391 [doi] AB - To understand metformin's effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was detected to explain the possible mechanisms. T2DM was induced by feeding rats with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ, 30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow; diabetic rats (DM) were fed on high-fat diet supplemented with or without metformin (METF) for 12 weeks (500 mg.kg(-1).d(-1)). Biochemical parameters were detected at the end of 24th weeks. FGFR1 expression and protein kinase B (Akt) phosphorylation in the pancreas and visceral adipose tissues were detected using either Western blot (WB) or immunohistochemistry (IHC). Serum FGF19 and FGF21 were measured using enzyme-linked immune sorbent assay (ELISA). Metformin treated DM rats showed improved glucose, lipid and bile acid metabolism. Besides, significantly decreased FGF19 and increased FGF21 were observed in DM+METF rats. DM rats showed significantly increased FGFR1 both in the pancreas and visceral adipose tissues. While in DM+METF rats, FGFR1 was almost remained at a normal level in the pancreas and increased in the visceral adipose tissue compared to that in DM rats. Besides, metformin treatment restores Akt phosphorylation in both tissues. The altered glucose and lipid profiles by metformin treatment may be associated with the increased circulating FGF21 and tissue-specific expressions of FGFR1. FAU - Wang, Yan AU - Wang Y AD - School of Medicine, Shandong University, Jinan 250013, Shandong Province, China. AD - Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong Province, China. FAU - Dang, Ningning AU - Dang N AD - Department of Dermatology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong Province, China. FAU - Sun, Pei AU - Sun P AD - Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong Province, China. FAU - Xia, Jin AU - Xia J AD - Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong Province, China. AD - Department of Medicine, Taishan Medical University, Taian 271000, Shandong Province, China. FAU - Zhang, Chunxue AU - Zhang C AD - Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong Province, China. AD - Department of Medicine, Taishan Medical University, Taian 271000, Shandong Province, China. FAU - Pang, Shuguang AU - Pang S AD - School of Medicine, Shandong University, Jinan 250013, Shandong Province, China. AD - Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong Province, China. AD - Department of Medicine, Taishan Medical University, Taian 271000, Shandong Province, China. LA - eng PT - Journal Article DEP - 20170411 PL - Japan TA - Endocr J JT - Endocrine journal JID - 9313485 RN - 0 (Hypoglycemic Agents) RN - 0 (fibroblast growth factor 21) RN - 62031-54-3 (Fibroblast Growth Factors) RN - 9100L32L2N (Metformin) RN - EC 2.7.10.1 (Fgfr1 protein, rat) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Diabetes Mellitus, Experimental/blood/*drug therapy MH - Diet, High-Fat MH - Fibroblast Growth Factors/*blood MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Intra-Abdominal Fat/drug effects/metabolism MH - Male MH - Metformin/pharmacology/*therapeutic use MH - Pancreas/drug effects/metabolism MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, Fibroblast Growth Factor, Type 1/*metabolism MH - Signal Transduction/drug effects OTO - NOTNLM OT - Diabetes OT - FGF21 OT - FGFR1 OT - Visceral adipose OT - beta cell EDAT- 2017/04/18 06:00 MHDA- 2018/03/27 06:00 CRDT- 2017/04/18 06:00 PHST- 2017/04/18 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2017/04/18 06:00 [entrez] AID - 10.1507/endocrj.EJ16-0391 [doi] PST - ppublish SO - Endocr J. 2017 May 30;64(5):543-552. doi: 10.1507/endocrj.EJ16-0391. Epub 2017 Apr 11.