The downregulation of type 1 diabetes susceptibility gene PGM1 induces metabolic imbalance and stress in pancreatic b cells
Year: 2026
Type: other
Abstract: Phosphoglucomutase1 (PGM1) is a type 1 diabetes susceptibility gene that potentially plays a key role in regulating central carbon metabolism in b cells. Previous work suggested that b cell PGM1 transcription is lowered after Coxsackievirus B4 infection. Thus, we hypothesized that decreased PGM1 levels disrupt β cell metabolic homeostasis and result in β cell fragility and type 1 diabetes. First, we showed that the synthetic dsRNA Polyinosinic:polycytidylic acid, or Poly(I:C) attenuated PGM1 transcription both in human islets and EndoC-bH1 cell line. At 5.5 mM glucose, PGM1 deficiency enhanced the rate of glycolysis, tricarboxylic acid (TCA) cycle, hexosamine, and pentose phosphate pathway. However, at 20 mM glucose, PGM1 deficient cells showed impaired mitochondrial respiration. Moreover, truncated N-glycans were enriched in PGM1 deficient cells, suggesting aberrant protein glycosylation. Autophagic flux, which was dependent on the lysosomal glycosylated protein function, was impaired in PGM1 deficient cells. Increased ER stress was evident in PGM1 deficient cells. Our results suggest that PGM1 is a metabolic regulator of pancreatic b cells. Its deficiency leads to metabolic imbalance and cellular stress, potentially augmenting type 1 diabetes development.
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7147504768
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