Saturated fatty acids contribute to beta-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca2+ depletion followed by notable store-operated Ca2+ entry. Subsequent elevation of cytosolic Ca2+ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca2+ uniporter (MCU) is the major route for Ca2+ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca2+ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal beta-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca2+ concentration ([Ca2+],) and reduced depolarization-triggered Ca2+ influx likely due to the inactivation of voltage-gated Ca2+ channels (VGCCs). Targeted reduction of MCU expression using RNA interference abolished mitochondrial superoxide production but exacerbated palmitate-induced [Ca2+], overload. Consequently, MCU knockdown aggravated blockage of autophagic degradation. In contrast, co-treatment with verapamil, a VGCC inhibitor, prevented palmitate-induced basal [Ca2+], elevation and defective [Ca2+], transients. Extracellular Ca2+ chelation as well as VGCC inhibitors effectively rescued autophagy defects and cytotoxicity. These observations suggest enhanced mitochondrial Ca2+ uptake via MCU upregulation is a mechanism by which pancreatic beta-cells are able to alleviate cytosolic Ca2+ overload and its detrimental consequences.

Over the past decades, gut microbiota has emerged as a critical modulator of human health and disease. Pregnancy involves substantial microbiota remodelling that influences offspring development, yet mechanisms linking maternal microbiota changes to gestational diabetes mellitus (GDM) remain unclear. The current literature lacks a comprehensive synthesis of pregnancy microbiota dynamics across healthy gestation to GDM, comparative human–murine analysis, and pregnancy-specific mechanistic frameworks distinct from type 2 diabetes models. This narrative review comprehensively synthesised evidence on gut microbiota composition in healthy pregnancy and GDM (2005–2025, NCBI PubMed) to identify convergent signatures and articulate pregnancy-specific mechanisms. Early pregnancy microbiota resembles non-pregnant individuals, whereas late pregnancy exhibits increased lactic acid-producing bacteria and reduced Firmicutes-to-Bacteroidetes (F/B) ratios. GDM exhibits pathological dysbiosis with elevated F/B ratios and reduced Bifidobacterium. Critically, GDM butyrate-producer patterns diverge from type 2 diabetes, suggesting pregnancy-specific mechanisms beyond glucose homeostasis. Despite these insights, methodological heterogeneity and cross-sectional designs constrain definitive conclusions. Longitudinal studies with standardised sequencing are essential to confirm consistent signatures and enable rational design of microbiota-modulating interventions (prebiotics, probiotics, synbiotics, postbiotics, diet) to optimise maternal health, prevent GDM, and support offspring development.

Beyond being one of the most widely prescribed medications for type 2 diabetes, metformin has been increasingly used during pregnancy for gestational diabetes and polyendocrine metabolic ovarian syndrome. While it is considered safe for pregnancy and lactation, metformin is known to induce gut microbial changes in non-pregnant individuals with type 2 diabetes, and maternal and offspring microbial alterations are known to influence offspring development. Therefore, understanding whether metformin drives microbiota changes beyond the confounding effects of maternal hyperglycaemia holds significant implications for maternal–foetal health. In this study, non-diabetic C57BL/6 mouse dams received either control or metformin treatment (5 mg/mL) in drinking water during pregnancy and lactation. Microbial profiling from faecal samples of dams at gestational day 15 and offspring at 6 weeks of age was analysed using 16S rRNA sequencing and an R-based pipeline. Metformin positively restructured dominant taxa associated with healthy pregnancy in dams, while inducing broad taxonomic changes in males and Bacteroidetes-dominant shifts in female offspring. Overall, maternal metformin treatment promoted short-chain fatty acid-producing taxa while suppressing potentially opportunistic bacteria, without compromising community richness. Further studies are required to elucidate the functional mechanisms underlying these shifts and their long-term implications for maternal–foetal health.