PMID- 25531651 OWN - NLM STAT- MEDLINE DCOM- 20150826 LR - 20240314 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 12 DP - 2014 TI - Chronic exercise increases plasma brain-derived neurotrophic factor levels, pancreatic islet size, and insulin tolerance in a TrkB-dependent manner. PG - e115177 LID - 10.1371/journal.pone.0115177 [doi] LID - e115177 AB - BACKGROUND: Physical exercise improves glucose metabolism and insulin sensitivity. Brain-derived neurotrophic factor (BDNF) enhances insulin activity in diabetic rodents. Because physical exercise modifies BDNF production, this study aimed to investigate the effects of chronic exercise on plasma BDNF levels and the possible effects on insulin tolerance modification in healthy rats. METHODS: Wistar rats were divided into five groups: control (sedentary, C); moderate- intensity training (MIT); MIT plus K252A TrkB blocker (MITK); high-intensity training (HIT); and HIT plus K252a (HITK). Training comprised 8 weeks of treadmill running. Plasma BDNF levels (ELISA assay), glucose tolerance, insulin tolerance, and immunohistochemistry for insulin and the pancreatic islet area were evaluated in all groups. In addition, Bdnf mRNA expression in the skeletal muscle was measured. PRINCIPAL FINDINGS: Chronic treadmill exercise significantly increased plasma BDNF levels and insulin tolerance, and both effects were attenuated by TrkB blocking. In the MIT and HIT groups, a significant TrkB-dependent pancreatic islet enlargement was observed. MIT rats exhibited increased liver glycogen levels following insulin administration in a TrkB-independent manner. CONCLUSIONS/SIGNIFICANCE: Chronic physical exercise exerted remarkable effects on insulin regulation by inducing significant increases in the pancreatic islet size and insulin sensitivity in a TrkB-dependent manner. A threshold for the induction of BNDF in response to physical exercise exists in certain muscle groups. To the best of our knowledge, these are the first results to reveal a role for TrkB in the chronic exercise-mediated insulin regulation in healthy rats. FAU - Jimenez-Maldonado, Alberto AU - Jimenez-Maldonado A AD - Centro Universitario de Investigaciones Biomedicas, Universidad de Colima, Colima, Mexico. FAU - de Alvarez-Buylla, Elena Roces AU - de Alvarez-Buylla ER AD - Centro Universitario de Investigaciones Biomedicas, Universidad de Colima, Colima, Mexico. FAU - Montero, Sergio AU - Montero S AD - Centro Universitario de Investigaciones Biomedicas, Universidad de Colima, Colima, Mexico. FAU - Melnikov, Valery AU - Melnikov V AD - Facultad de Medicina, Universidad de Colima, Colima, Mexico. FAU - Castro-Rodriguez, Elena AU - Castro-Rodriguez E AD - Centro Universitario de Investigaciones Biomedicas, Universidad de Colima, Colima, Mexico. FAU - Gamboa-Dominguez, Armando AU - Gamboa-Dominguez A AD - Depto de Patologia, Instituto Nacional de Nutricion y Ciencias Medicas "Salvador Zubiran," Mexico City, Mexico D.F. FAU - Rodriguez-Hernandez, Alejandrina AU - Rodriguez-Hernandez A AD - Facultad de Medicina, Universidad de Colima, Colima, Mexico. FAU - Lemus, Monica AU - Lemus M AD - Centro Universitario de Investigaciones Biomedicas, Universidad de Colima, Colima, Mexico. FAU - Murguia, Jesus Muniz AU - Murguia JM AD - Centro Universitario de Investigaciones Biomedicas, Universidad de Colima, Colima, Mexico. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141222 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Insulin) RN - 0 (RNA, Messenger) RN - 9005-79-2 (Glycogen) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM EIN - PLoS One. 2015;10(3):e0119047. PMID: 25756350 MH - Animals MH - Area Under Curve MH - Brain-Derived Neurotrophic Factor/*blood/genetics/metabolism MH - Glucose Tolerance Test MH - Glycogen/metabolism MH - Immunohistochemistry MH - Insulin/*metabolism/pharmacology MH - Insulin Resistance MH - Islets of Langerhans/anatomy & histology/*pathology MH - Liver/drug effects/metabolism MH - Male MH - Muscle, Skeletal/metabolism MH - Organ Size MH - Physical Conditioning, Animal MH - RNA, Messenger/metabolism MH - ROC Curve MH - Rats MH - Rats, Wistar MH - Receptor, trkB/antagonists & inhibitors/genetics/*metabolism PMC - PMC4274083 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/12/23 06:00 MHDA- 2015/08/27 06:00 PMCR- 2014/12/22 CRDT- 2014/12/23 06:00 PHST- 2014/02/19 00:00 [received] PHST- 2014/11/19 00:00 [accepted] PHST- 2014/12/23 06:00 [entrez] PHST- 2014/12/23 06:00 [pubmed] PHST- 2015/08/27 06:00 [medline] PHST- 2014/12/22 00:00 [pmc-release] AID - PONE-D-14-07919 [pii] AID - 10.1371/journal.pone.0115177 [doi] PST - epublish SO - PLoS One. 2014 Dec 22;9(12):e115177. doi: 10.1371/journal.pone.0115177. eCollection 2014.