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Updated: Aug 7, 2026

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Pancreatic beta cells lack a low glucose and O2-inducible mitochondrial protein that augments cell survival
1Department of Biochemistry and Molecular Biology, University of Chicago, and The Howard Hughes Medical Institute, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Abstract:
beta cell failure is a common denominator of diabetes. Susceptibility to stress-induced apoptosis may underlie beta cell failure and/or hamper islet transplantation therapy. The causal basis is not well understood. In efforts to identify important differences in gene expression in alpha vs. beta cells, a gene termed HIMP1 (Hypoglycemia/hypoxia Inducible Mitochondrial Protein, or HIG1) has been cloned from an alpha cell cDNA library. It is a member of a well conserved eukaryote protein family. In mice, its two alternatively spliced products each form a transmembrane loop, having an N(outside)-C(outside) orientation and are expressed highly in the mitochondrial inner membrane in several tissues including heart and pancreatic alpha cells, but not in beta cells. Ectopic expression of HIMP1 in MIN6 beta cells protects the cells from apoptosis induced by several stimuli and prolongs their survival. These results suggest an important role for HIMP1 in stress protective programs in mitochondria.
Insights
Scientists identified a mitochondrial protein, HIMP1 (Hypoglycemia/hypoxia Inducible Mitochondrial Protein), that protects pancreatic beta cells from stress-induced apoptosis. This discovery offers potential new avenues for treating diabetes and improving islet transplantation outcomes.
Area of Science:
- Cell Biology
- Endocrinology
- Mitochondrial Biology
Background:
- Beta cell failure is a key factor in diabetes development.
- Understanding the molecular mechanisms of beta cell apoptosis is crucial for therapeutic strategies.
- Differences in gene expression between alpha and beta cells are not fully understood.
Purpose of the Study:
- To identify genes with differential expression between pancreatic alpha and beta cells.
- To investigate the role of the identified gene, HIMP1, in beta cell survival and stress response.
Main Methods:
- Cloning of HIMP1 (Hypoglycemia/hypoxia Inducible Mitochondrial Protein) from an alpha cell cDNA library.
- Analysis of HIMP1 expression and localization in mouse tissues and pancreatic cells.
- Ectopic expression of HIMP1 in MIN6 beta cells to assess its functional impact on apoptosis.
Main Results:
- HIMP1, a mitochondrial inner membrane protein, is highly expressed in pancreatic alpha cells but not in beta cells.
- Ectopic expression of HIMP1 in beta cells conferred protection against apoptosis induced by various stressors.
- HIMP1 expression prolonged the survival of beta cells under stress conditions.
Conclusions:
- HIMP1 plays a significant role in mitochondrial stress protective mechanisms.
- HIMP1 may be a potential therapeutic target for enhancing beta cell survival in diabetes and improving islet transplantation success.
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