Streptozotocin produces oxidative stress, inflammation and decreases BDNF concentrations to induce apoptosis of RIN5F cells and type 2 diabetes mellitus in Wistar rats.
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.



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.



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-α 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.



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-αlevels 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.



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.
BioScience Research Centre, Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India. Electronic address: siresha99@googlemail.com.
Siresha
S
Bathina
National Institute of Pharmaceutical Education and Research, Hyderabad, India.
Nanduri
N
Srinivas
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.
Undurti N
UN
Das
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D009536:Niacinamide; D013311:Streptozocin
BDNF; Diabetes mellitus; Hyperglycemia; Oxidative stress; Protein expression