PMID- 28315336 OWN - NLM STAT- MEDLINE DCOM- 20170605 LR - 20171128 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 486 IP - 2 DP - 2017 Apr 29 TI - Streptozotocin produces oxidative stress, inflammation and decreases BDNF concentrations to induce apoptosis of RIN5F cells and type 2 diabetes mellitus in Wistar rats. PG - 406-413 LID - S0006-291X(17)30512-0 [pii] LID - 10.1016/j.bbrc.2017.03.054 [doi] AB - BACKGROUND: Neurodegenerative disorders, such as deficits in learning, memory and cognition and Alzheimer's disease are associated with diabetes mellitus. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor and is known to possess anti-obesity, anti-diabetic actions and is believed to have a role in memory and Alzheimer's disease. OBJECTIVE: To investigate whether STZ can reduce BDNF production by rat insulinoma (RIN5F) cells in vitro and decrease BDNF levels in the pancreas, liver and brain in vivo. METHODS: Streptozotocin (STZ)-induced cytotoxicity to RIN5F cells in vitro and type 2 DM in Wistar rats was employed in the present study. Cell viability, activities of various anti-oxidants and secretion of BDNF by RIN5F cells in vitro were measured using MTT assay, biochemical methods and ELISA respectively. In STZ-induced type 2 DM rats: plasma glucose, interleukin-6 and tumor necrosis factor-alpha levels and BDNF protein expression in the pancreas, liver and brain tissues were measured. In addition, neuronal count and morphology in the hippocampus and hypothalamus areas was assessed. RESULTS: STZ-induced suppression of RIN5F cell viability was abrogated by BDNF. STZ suppressed BDNF secretion by RIN5F cells in vitro. STZ-induced type 2 DM rats showed hyperglycemia, enhanced plasma IL-6 and TNF-alphalevels and reduced plasma and pancreas, liver and brain tissues (P < 0.001) and increased oxidative stress compared to untreated control. Hypothalamic and hippocampal neuron in STZ-treated animals showed a decrease in the number of neurons and morphological changes suggesting of STZ cytotoxicity. CONCLUSIONS: The results of the present study suggest that STZ is not only cytotoxic to pancreatic beta cells but also to hypothalamic and hippocampal neurons by inducing oxidative stress. STZ ability to suppress BDNF production by pancreas, liver and brain tissues suggests that impaired memory, learning, and cognitive dysfunction seen in diabetes mellitus could be due to BDNF deficiency. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Bathina, Siresha AU - Bathina S AD - BioScience Research Centre, Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India. Electronic address: siresha99@googlemail.com. FAU - Srinivas, Nanduri AU - Srinivas N AD - National Institute of Pharmaceutical Education and Research, Hyderabad, India. FAU - Das, Undurti N AU - Das UN AD - BioScience Research Centre, Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India; UND Life Sciences, 2221, NW 5th St, Battle Ground, WA 98604, USA. Electronic address: undurti@lipidworld.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170315 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Blood Glucose) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - 25X51I8RD4 (Niacinamide) RN - 5W494URQ81 (Streptozocin) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Blood Glucose/metabolism MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*genetics/metabolism MH - Cell Line MH - Cell Survival/drug effects MH - Diabetes Mellitus, Experimental/chemically induced/*genetics/metabolism/pathology MH - Gene Expression Regulation MH - Hippocampus/drug effects/metabolism/pathology MH - Hypothalamus/drug effects/metabolism/pathology MH - Inflammation MH - Insulin-Secreting Cells/*drug effects/metabolism/pathology MH - Interleukin-6/genetics/metabolism MH - Liver/drug effects/metabolism/pathology MH - Male MH - Neurons/drug effects/metabolism/pathology MH - Niacinamide/administration & dosage MH - Oxidative Stress/drug effects MH - Rats MH - Rats, Wistar MH - Streptozocin/*administration & dosage MH - Tumor Necrosis Factor-alpha/genetics/metabolism OTO - NOTNLM OT - BDNF OT - Diabetes mellitus OT - Hyperglycemia OT - Oxidative stress OT - Protein expression EDAT- 2017/03/21 06:00 MHDA- 2017/06/06 06:00 CRDT- 2017/03/19 06:00 PHST- 2017/03/12 00:00 [received] PHST- 2017/03/13 00:00 [accepted] PHST- 2017/03/21 06:00 [pubmed] PHST- 2017/06/06 06:00 [medline] PHST- 2017/03/19 06:00 [entrez] AID - S0006-291X(17)30512-0 [pii] AID - 10.1016/j.bbrc.2017.03.054 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2017 Apr 29;486(2):406-413. doi: 10.1016/j.bbrc.2017.03.054. Epub 2017 Mar 15.