title: Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet.
abstract: Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100mg/kg doses (i.p.): the first dose was administered at approximately 2weeks following the initiation of daily GE (20mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes.
authors.affiliation: Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382, USA. Electronic address: tlguo1@uga.edu.
authors.forename: Tai L
authors.initials: TL
authors.lastname: Guo
authors.affiliation: Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382, USA; Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China.
authors.forename: Yunbiao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xiong
authors.affiliation: Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ling
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001786:Blood Glucose / Q000032:analysis / Q000276:immunology*; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000276:immunology; D004032:Diet; D005260:Female; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000276:immunology; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D048789:Phytoestrogens / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018709:Statistics, Nonparametric; D013311:Streptozocin / Q000008:administration & dosage*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D001786:Blood Glucose; D048789:Phytoestrogens; D013311:Streptozocin; D019833:Genistein
keywords: Diabetes; Genistein; Immunomodulation; Male B6C3F1 mice; Streptozotocin