Obesity-Associated Gestational Diabetes Promotes Cellular Heterogeneity and Dysfunction in Neonatal Offspring-Islets.

Area of Science:

• Endocrinology
• Metabolic Health
• Developmental Biology

Background:

• Maternal overnutrition during pregnancy impacts offspring metabolic health.
• The specific effects of a Western diet (WD) on neonatal islet development are unclear.

Purpose of the Study:

• To investigate the influence of maternal WD exposure on neonatal islet cell development and heterogeneity.
• To understand the molecular mechanisms linking maternal diet to offspring metabolic dysfunction.

Main Methods:

• Established a WD-induced gestational diabetes mellitus (GDM) rat model.
• Assessed glucose homeostasis (blood glucose, serum insulin) and islet function (insulin secretion).
• Utilized single-cell RNA sequencing (scRNA-seq) to analyze islet cell heterogeneity and gene expression.

Main Results:

• Maternal WD induced GDM, leading to offspring hypoglycemia, hyperinsulinemia, and impaired glucose homeostasis.
• scRNA-seq revealed imbalanced alpha/beta cell subsets in offspring islets, with expanded mature subsets.
• Offspring beta cells exhibited metabolic hyperactivity, mitochondrial dysfunction, and endoplasmic reticulum stress.

Conclusions:

• Metabolic dysregulation from maternal WD-induced GDM transmits to offspring, disrupting islet cell balance and accelerating maturation.
• Accelerated islet development in offspring is linked to beta cell organelle damage.
• Findings suggest early nutritional interventions may mitigate intergenerational diabetes transmission.