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Publication
Sex differences in insulin resistance, but not peripheral neuropathy, in a
diet-induced prediabetes mouse model.
Authors Elzinga SE, Savelieff MG, O'Brien PD, Mendelson FE, Hayes JM, Feldman EL
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Disease models & mechanisms
Year 2021
Date Published 4/1/2021
Volume : Pages 14 : Not Specified
PubMed Reference 33692086
Abstract Peripheral neuropathy (PN) is a common complication of prediabetes and diabetes
and is an increasing problem worldwide. Existing PN treatments rely solely on
glycemic control, which is effective in type 1 but not type 2 diabetes. Sex
differences in response to anti-diabetic drugs further complicate the
identification of effective PN therapies. Preclinical research has been
primarily carried out in males, highlighting the need for increased sex
consideration in PN models. We previously reported PN sex dimorphism in obese
leptin-deficient ob/ob mice. This genetic model is inherently limited, however,
owing to leptin's role in metabolism. Therefore, the current study goal was to
examine PN and insulin resistance in male and female C57BL6/J mice fed a
high-fat diet (HFD), an established murine model of human prediabetes lacking
genetic mutations. HFD mice of both sexes underwent longitudinal phenotyping and
exhibited expected metabolic and PN dysfunction compared to standard diet
(SD)-fed animals. Hindpaw thermal latencies to heat were shorter in HFD females
versus HFD males, as well as SD females versus males. Compared to HFD males,
female HFD mice exhibited delayed insulin resistance, yet still developed the
same trajectory of nerve conduction deficits and intraepidermal nerve fiber
density loss. Subtle differences in adipokine levels were also noted by sex and
obesity status. Collectively, our results indicate that although females retain
early insulin sensitivity upon HFD challenge, this does not protect them from
developing the same degree of PN as their male counterparts. This article has an
associated First Person interview with the first author of the paper.




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