# Multi-Omics Analysis of a Spontaneous Type 2 Diabetes Model in Myodes rufocanus and Its Underlying Mechanisms

## TL;DR

Researchers identified a new spontaneous type 2 diabetes model in voles and linked COX14 downregulation to mitochondrial dysfunction and β-cell failure.

## Contribution

The study introduces Myodes rufocanus as a novel spontaneous T2DM model and identifies COX14 downregulation as a potential contributor to β-cell dysfunction.

## Key findings

- Myodes rufocanus exhibits hallmark T2DM features including hyperglycemia and insulin resistance.
- COX14 downregulation correlates with mitochondrial dysfunction and impaired insulin secretion in β-cells.
- Suppressed Nrf2–HO-1 signaling and elevated apoptotic markers suggest increased β-cell injury.

## Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, progressive β-cell dysfunction, and insulin resistance. While numerous chemically induced and transgenic rodent models exist, spontaneous models recapitulating natural type 2 diabetes mellitus (T2DM) progression remain scarce. Here, we characterize Myodes rufocanus as a novel spontaneous T2DM model through comprehensive assessments of 18-week-old male F6 voles, demonstrating hallmark diabetic features including weight gain, hyperphagia, polydipsia, hyperglycemia, insulin resistance, and dyslipidemia. Pancreatic transcriptomic profiling revealed pronounced COX14 (cytochrome c oxidase assembly factor 14) downregulation, as validated by qPCR and Western blotting in pancreatic tissue and MIN6 β-cells. MIN6 cells under chronic high-glucose conditions (30 mM) exhibited diminished mitochondrial membrane potential, impaired ATP biosynthesis, elevated reactive oxygen species, and attenuated glucose-stimulated insulin secretion, with consistent COX14 downregulation suggesting potential association with mitochondrial dysfunction. Additionally, suppressed Nrf2–HO-1 antioxidant signaling appeared to compound cellular injury, with intrinsic apoptotic pathway activation indicated by elevated Bax/Bcl-2 ratios and caspase-3 activity. These findings establish M. rufocanus as a valuable spontaneous T2DM model and implicate COX14 downregulation as a potential correlate of mitochondrial impairment and β-cell failure in diabetes pathogenesis.