Metabolic rate and insulin-independent glucose uptake increase in a TDP-43^Q331K mouse model of amyotrophic lateral sclerosis.

ABSTRACT: Impaired glucose regulation is increasingly recognised in amyotrophic lateral sclerosis (ALS), yet the precise mechanisms remain unclear. Here, we investigated energy balance and glucose control in TAR DNA-binding protein 43 (TDP-43)^Q331K mice, a model of ALS, at both the early and late symptomatic stages of disease. Mutant TDP-43^Q331K mice and non-transgenic controls underwent indirect calorimetry, as well as intraperitoneal glucose, insulin, and glucagon tolerance testing. We also examined plasma hormone levels and quantified α- and β-cell areas in pancreatic islets. Throughout disease progression, TDP-43^Q331K mice exhibited elevated metabolic rates, with a transient increase in food intake at the early stages. At the later stages of disease, heightened g

SUBMITTER: McDonald TS 

PROVIDER: S-EPMC11849610 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature