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High-fat diet impacts more changes in beta-cell compared to alpha-cell transcriptome.

Rodolphe Dusaulcy1, Sandra Handgraaf1, Florian Visentin1

  • 1Molecular Diabetes Laboratory, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland.

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Pancreatic alpha cells show minimal transcriptome changes in diabetic mice, unlike beta cells. Three new genes involved in cellular stress and exocytosis were identified in diabetic alpha cells.

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Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Molecular Biology

Background:

  • Understanding endocrine cell dysfunction in diabetes is key to addressing metabolic abnormalities.
  • The role of glucagon necessitates a deeper understanding of alpha cell function in diabetes.
  • Diet-induced obesity is a relevant model for studying diabetes-related cellular changes.

Purpose of the Study:

  • To characterize molecular alterations in alpha cells of diabetic mice.
  • To compare the transcriptomic response of alpha and beta cells to a high-fat diet.
  • To identify novel genes affected in diabetic alpha cells.

Main Methods:

  • RNA sequencing of sorted alpha and beta cells from mice on low-fat and high-fat diets.
  • Utilized a transgenic mouse model for efficient cell sorting.
  • Analyzed transcriptomic data to identify differentially expressed genes.

Main Results:

  • Diabetic alpha cells exhibited minor transcriptome variations compared to controls.
  • Identified 11-39 differentially expressed genes, including potential contaminants.
  • Discovered three novel genes (Upk3a, Adcy1, Dpp6) altered in diabetic alpha cells, linked to cellular stress and exocytosis.
  • Beta cells showed significant transcriptomic alterations related to proliferation and secretion.

Conclusions:

  • Alpha cell transcriptomes are less affected by high-fat diets than beta cell transcriptomes.
  • Diabetic alpha cells adapt through mechanisms involving cellular stress and exocytosis.
  • Beta cells undergo more profound molecular changes in response to diet-induced diabetes.