Young adult male LEW.1WR1 rats have reduced beta cell area and develop glucose intolerance

Quiana C Wilkerson-Vidal; Madushika Wimalarathne; Genoah Collins; James Gerard Wolfsberger; Amelia Clopp; Luis Mercado; Evann Fowler; Helen Gibson; Victoria McConnell; Sidney Martin; Emily C Hunt; Bernhard Vogler; Sharifa T Love-Rutledge

doi:10.1016/j.mce.2022.111837

Young adult male LEW.1WR1 rats have reduced beta cell area and develop glucose intolerance

Mol Cell Endocrinol. 2023 Feb 15:562:111837. doi: 10.1016/j.mce.2022.111837. Epub 2022 Dec 20.

Affiliations

¹ The University of Alabama Huntsville, Department of Chemistry, Materials Science Building 201, John Wright Drive, Huntsville, AL, 35899, USA; The University of Alabama in Huntsville, Department of Biology, Shelby Center for Science and Technology, 301 Sparkman Drive, Huntsville, AL, 35899, USA. Electronic address: qcv0001@uah.edu.
² The University of Alabama Huntsville, Department of Chemistry, Materials Science Building 201, John Wright Drive, Huntsville, AL, 35899, USA; The University of Alabama in Huntsville, Department of Biology, Shelby Center for Science and Technology, 301 Sparkman Drive, Huntsville, AL, 35899, USA. Electronic address: mmw0026@uah.edu.
³ The University of Alabama Huntsville, Department of Chemistry, Materials Science Building 201, John Wright Drive, Huntsville, AL, 35899, USA. Electronic address: gcollins102@gmail.com.
⁴ The University of Alabama Huntsville, Department of Chemistry, Materials Science Building 201, John Wright Drive, Huntsville, AL, 35899, USA. Electronic address: jw0011@uah.edu.
⁵ The University of Alabama in Huntsville, Department of Biology, Shelby Center for Science and Technology, 301 Sparkman Drive, Huntsville, AL, 35899, USA. Electronic address: amelia.clopp@gmail.com.
⁶ The University of Alabama in Huntsville, Department of Biology, Shelby Center for Science and Technology, 301 Sparkman Drive, Huntsville, AL, 35899, USA. Electronic address: ldm0020@uah.edu.
⁷ The University of Alabama in Huntsville, Department of Biology, Shelby Center for Science and Technology, 301 Sparkman Drive, Huntsville, AL, 35899, USA. Electronic address: etf0004@uah.edu.
⁸ The University of Alabama in Huntsville, Department of Biology, Shelby Center for Science and Technology, 301 Sparkman Drive, Huntsville, AL, 35899, USA. Electronic address: hg0016@uah.edu.
⁹ The University of Alabama in Huntsville, Department of Biology, Shelby Center for Science and Technology, 301 Sparkman Drive, Huntsville, AL, 35899, USA. Electronic address: vjm0001@uah.edu.
¹⁰ The University of Alabama Huntsville, Department of Chemistry, Materials Science Building 201, John Wright Drive, Huntsville, AL, 35899, USA; The University of Alabama in Huntsville, Department of Biology, Shelby Center for Science and Technology, 301 Sparkman Drive, Huntsville, AL, 35899, USA. Electronic address: sm0188@uah.edu.
¹¹ The University of Alabama Huntsville, Department of Chemistry, Materials Science Building 201, John Wright Drive, Huntsville, AL, 35899, USA. Electronic address: ech0012@uah.edu.
¹² The University of Alabama Huntsville, Department of Chemistry, Materials Science Building 201, John Wright Drive, Huntsville, AL, 35899, USA. Electronic address: voglerb@uah.edu.
¹³ The University of Alabama Huntsville, Department of Chemistry, Materials Science Building 201, John Wright Drive, Huntsville, AL, 35899, USA. Electronic address: sharifa.love-rutledge@uah.edu.

PMID: 36549462
DOI: 10.1016/j.mce.2022.111837

Abstract

Prediabetes affects 1 in 3 American adults and is characterized by insulin resistance, insulin hypersecretion, and impaired glucose tolerance. Weanling LEW.1WR1 (1WR1) rats have increased blood insulin concentrations, so we hypothesized that young adult 1WR1 rats would develop impaired glucose tolerance due to the poor regulation of insulin. We monitored glucose tolerance, insulin tolerance, and weight gain for 10 weeks to assess if there was a decline in glucose processing over time. 1WR1 rats were significantly more glucose intolerant after 8 weeks. 1WR1 rats had increased body mass, yet abdominal fat mass was not significantly increased. Although the 1WR1 rats had increased circulating insulin and glucagon protein levels, 1WR1 rat beta cell area was significantly reduced. There may be underlying insulin resistance as evidenced by dysfunctional insulin regulation during fasting. Understanding the metabolic phenotype of this rat model can provide insight into the human pathophysiological changes that increase susceptibility to glucose intolerance and prediabetes.

Keywords: Glucose intolerance; Hyperinsulinemia; Insulin resistance; Islets; Metabolomics.

MeSH terms

Animals
Blood Glucose / metabolism
Glucose / metabolism
Glucose Intolerance*
Humans
Hyperinsulinism*
Insulin / metabolism
Insulin Resistance*
Male
Prediabetic State*
Rats
Rats, Inbred Lew

Substances

Blood Glucose
Glucose
Insulin