Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy

Female mice have been found to be resistant to streptozotocin (STZ)-induced diabetes, and pre-clinical research related to diabetic complications commonly omits females. The purpose of this study was to develop a method to induce diabetes in female mice, and to determine if retinas of diabetic femal...

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Bibliographic Details
Published in:PloS one 2020-09, Vol.15 (9), p.e0238727
Main Authors: Saadane, Aicha, Lessieur, Emma M, Du, Yunpeng, Liu, Haitao, Kern, Timothy S
Format: Article
Language:English
Subjects:
Abnormalities
Analysis
Animal research models
Animals
Antibodies
Biology and Life Sciences
Capillaries
Capillaries - drug effects
Capillaries - metabolism
Complications
Complications and side effects
Degeneration
Development and progression
Diabetes
Diabetes mellitus
Diabetes Mellitus, Experimental - chemically induced
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - pathology
Diabetes Mellitus, Experimental - physiopathology
Diabetic retinopathy
Diabetic Retinopathy - pathology
Diabetic Retinopathy - physiopathology
Disease Models, Animal
Disease sex factors
Female
Females
Gender differences
Gene Expression Regulation - drug effects
Glucose
Hyperglycemia
Inflammation
Infrared imaging systems
Injection
Insulin
Intercellular adhesion molecule 1
Laboratory animals
Leukocytes - drug effects
Male
Males
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Nitric Oxide Synthase Type II - metabolism
Nitric-oxide synthase
Oxidative stress
Oxidative Stress - drug effects
Penicillin
Physical Sciences
Physiological aspects
Research and Analysis Methods
Retina
Retina - drug effects
Retina - pathology
Retinopathy
Risk factors
Sex Characteristics
Streptozocin
Streptozocin - pharmacology
Superoxide
Variance analysis
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Summary:Female mice have been found to be resistant to streptozotocin (STZ)-induced diabetes, and pre-clinical research related to diabetic complications commonly omits females. The purpose of this study was to develop a method to induce diabetes in female mice, and to determine if retinas of diabetic female mice develop molecular changes and histopathological abnormalities comparable to those which develop in male diabetic mice. To induce diabetes, animals of both sexes received daily intraperitoneal (i.p.) injection of STZ for 5 consecutive days at 55 mg/kg BW (a dose that is known to induce diabetes in male mice) or for females, 75 mg/kg BW of STZ. Retinal abnormalities that have been implicated in the development of the retinopathy (superoxide generation and expression of inflammatory proteins, iNOS and ICAM-1) were evaluated at 2 months of diabetes, and retinal capillary degeneration was evaluated at 8 months of diabetes. Daily i.p. injection of STZ for 5 consecutive days at a concentration of 55 mg/kg BW was sufficient to induce diabetes in 100% of male mice, but only 33% of female mice. However, females did become hyperglycemic when the dose of STZ administered was increased to 75 mg/kg BW. The resulting STZ-induced hyperglycemia in female and male mice was sustained for at least 8 months. After induction of the diabetes, both sexes responded similarly with respect to the oxidative stress, expression of iNOS, and degeneration of retinal capillaries, but differed in the limited population evaluated with respect to expression of ICAM-1. The resistance of female mice to STZ-induced diabetes can be overcome by increasing the dose of STZ used. Female mice can, and should, be included in pre-clinical studies of diabetes and its complications.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0238727