Maternal Protein Restriction Increases Autophagy in the Pancreas of Newborn Rats

Area of Science:

• Endocrinology
• Developmental Biology
• Cellular Biology

Background:

• Maternal low-protein diets are linked to offspring type 2 diabetes susceptibility.
• The underlying mechanisms of pancreatic injury in intrauterine growth restriction (IUGR) remain unclear.
• Autophagy and endoplasmic reticulum (ER) stress are implicated in pancreatic development and disease.

Purpose of the Study:

• To investigate alterations in pancreatic autophagy in IUGR rats.
• To evaluate the role of mammalian target of rapamycin complex 1 (mTORC1) signaling in IUGR-associated pancreatic changes.
• To assess the presence and extent of ER stress in the pancreas of IUGR offspring.

Main Methods:

• Established a maternal protein restriction rat model to induce IUGR.
• Quantified autophagy markers (LC3II, Beclin1) using transmission electron microscopy, immunofluorescence, qRT-PCR, and Western blotting.
• Assessed mTORC1 signaling activity and ER stress markers via Western blotting, immunohistochemistry, and qRT-PCR.

Main Results:

• IUGR offspring exhibited significantly increased levels of autophagy markers LC3II and Beclin1 compared to controls.
• mTORC1 signaling activity was decreased in the pancreas of IUGR rats.
• Evidence of ER stress was confirmed in pancreatic beta cells of IUGR offspring.

Conclusions:

• Maternal protein restriction enhances pancreatic autophagy in IUGR newborns.
• ER stress is induced in the beta cells of IUGR rat pancreases.
• These cellular changes may adversely affect pancreas development and contribute to metabolic dysfunction.