# Therapeutic potential of magnesium sulfate in improving duodenal homeobox 1 and PPARG coactivator 1 alpha genes to reduce pancreatic insulin resistance in F1 offspring of diabetic rats

**Authors:** Mahtab Ghanbari Rad, Hossein Rezazadeh, Mohammadreza Sharifi, Nepton Soltani

PMC · DOI: 10.22038/ijbms.2025.84255.18232 · Iranian Journal of Basic Medical Sciences · 2025-01-01

## TL;DR

This study shows magnesium sulfate can reduce insulin resistance in diabetic rats and their offspring by improving key pancreatic genes.

## Contribution

The novel finding is that magnesium sulfate improves Pdx1 and Pgc1α gene expression to reduce pancreatic insulin resistance in offspring of diabetic rats.

## Key findings

- MgSO4 treatment reduced HOMA-IR, TyG index, and glucagon levels in diabetic rats and their offspring.
- MgSO4 increased glucose infusion rate and Pdx1 gene expression, indicating improved insulin sensitivity.
- Treatment improved pancreatic β cell survival and regeneration through gene expression changes.

## Abstract

The study aimed to investigate the role of magnesium sulfate (MgSO4) therapy in pancreatic insulin resistance (IR) in diabetic and non-diabetic rats and their F1 offspring following administration of a high-fat diet (HFD).

Diabetes was induced in the subjects through a combination of HFD and a low dose of streptozotocin (STZ). The male and female diabetic animals were divided into three groups: diabetic control (DC), insulin, and MgSO4 (Mg) treated groups. One group of both sexes was kept as non-diabetic control (NDC) and fed a regular diet. Their F1 offspring were fed a regular diet for four months. Euglycemic hyperinsulinemic clamp (HEC) tests were performed on the parents and their F1 offspring. Blood samples were taken every hour during the clamp to measure changes in glucagon levels. Pancreas tissue was isolated, and the expression of pancreatic and duodenal homeobox 1(Pdx1) and PPARG coactivator 1 alpha (Pgc1α) genes was measured in all groups.

Treatment with MgSO4 or insulin decreased HOMA-IR, TyG index, BGL, ITT, HbA1c, glucagon level, Pgc1α expression, and increased glucose infusion rate (GIR), body weight, Pdx1 gene expression, and insulin level in diabetic parents and their F1 offspring compared to the DC group. These changes suggest a decrease in IR. Additionally, alterations in IR have decreased. Also, changes in the expression of these genes indicate a positive impact on the survival and regeneration rate of pancreatic β cells.

MgSO4 showed beneficial effects in treating glucose metabolism and improving IR.

## Linked entities

- **Genes:** PDX1 (pancreatic and duodenal homeobox 1) [NCBI Gene 3651], PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891]
- **Chemicals:** magnesium sulfate (PubChem CID 24083), streptozotocin (PubChem CID 29327), glucagon (PubChem CID 16132283)
- **Diseases:** diabetes (MONDO:0005015)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Gcg (glucagon) [NCBI Gene 24952] {aka GLP-1, Glp1, Glp2}, Pdx1 (pancreatic and duodenal homeobox 1) [NCBI Gene 29535] {aka Idx1, Ipf1, Stf1}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}
- **Diseases:** Euglycemic hyperinsulinemic (MESH:D044903), IR (MESH:D007333), Diabetes (MESH:D003920)
- **Chemicals:** STZ (MESH:D013311), Mg (MESH:D008278), fat (MESH:D005223), glucose (MESH:D005947)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12340409/full.md

## References

62 references — full list in the complete paper: https://tomesphere.com/paper/PMC12340409/full.md

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Source: https://tomesphere.com/paper/PMC12340409