Abstract
Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no change in circulating glucagon levels or gluconeogenesis. The effect was dose-dependent, took effect by two weeks, and was reversed within three weeks after removal. Glimepiride elicited the same effects in all strains evaluated: four wild-type strains, as well as the transgenic Grn−/− and diabetic db/db mice. Our findings suggest that the use of glimepiride as a hypoglycemic agent in mice should proceed with caution and may have broader implications about mouse models as a proxy to study the human pharmacopeia.
Document Type
Article
Publication Date
10-29-2018
Digital Object Identifier (DOI)
https://doi.org/10.1155/2018/1251345
Funding Information
Grant support came from NIH-NIA grants AG042419, AG057187, and AG050146.
Related Content
The data used to support the findings of this study are available from the corresponding author upon request.
Repository Citation
Niedowicz, Dana M.; Özcan, Sabire; and Nelson, Peter T., "Glimepiride Administered in Chow Reversibly Impairs Glucose Tolerance in Mice" (2018). Sanders-Brown Center on Aging Faculty Publications. 122.
https://uknowledge.uky.edu/sbcoa_facpub/122
Included in
Endocrine System Commons, Endocrinology, Diabetes, and Metabolism Commons, Geriatrics Commons, Neurosciences Commons, Pharmaceutical Preparations Commons
Notes/Citation Information
Published in Journal of Diabetes Research, v. 2018, article ID 1251345, p. 1-12.
© 2018 Dana M. Niedowicz et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.