Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet

PLoS One. 2021 Mar 17;16(3):e0248065. doi: 10.1371/journal.pone.0248065. eCollection 2021.

Abstract

Excessive sodium salt (NaCl) or fat intake is associated with a variety of increased health risks. However, whether excessive NaCl intake accompanied by a high-fat diet (HFD) affects glucose metabolism has not been elucidated. In this study, C57BL/6J male mice were fed a normal chow diet (NCD), a NCD plus high-NaCl diet (NCD plus NaCl), a HFD, or a HFD plus high-NaCl diet (HFD plus NaCl) for 30 weeks. No significant differences in body weight gain, insulin sensitivity, and glucose tolerance were observed between NCD-fed and NCD plus NaCl-fed mice. In contrast, body and liver weights were decreased, but the weight of epididymal white adipose tissue was increased in HFD plus NaCl-fed compared to HFD-fed mice. HFD plus NaCl-fed mice had lower plasma glucose levels in an insulin tolerance test, and showed higher plasma glucose and lower plasma insulin levels in an intraperitoneal glucose tolerance test compared to HFD-fed mice. The β-cell area and number of islets were decreased in HFD plus NaCl-fed compared to HFD-fed mice. Increased Ki67-positive β-cells, and increased expression levels of Ki67, CyclinB1, and CyclinD1 mRNA in islets were observed in HFD-fed but not HFD plus NaCl-fed mice when compared to NCD-fed mice. Our data suggest that excessive NaCl intake accompanied by a HFD exacerbates glucose intolerance, with impairment in insulin secretion caused by the attenuation of expansion of β-cell mass in the pancreas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Diet, High-Fat*
  • Energy Metabolism / physiology
  • Glucose Intolerance / metabolism*
  • Glucose Tolerance Test
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Insulin Secretion / physiology*
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Mice
  • Sodium Chloride, Dietary*

Substances

  • Blood Glucose
  • Insulin
  • Sodium Chloride, Dietary

Grants and funding

This study was supported by JSPS KAKENHI Grant Numbers JP17K17803 and 19K20180 to HT; and Chukyo Longevity Foundation in 2019 to HT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.