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Pancreatic beta cell lines and their applications in diabetes mellitus research
Masa Skelin1, Marjan Rupnik, Avrelija Cencic
1University of Maribor, Slovenia.
Abstract:
During the past 30 years great effort has been put into establishing an insulin-secreting beta cell line that retains normal regulation of insulin secretion, but only few of these attempts have been successful. To overcome the limited availability of primary beta cells and to include the principles of the 3Rs into the field of diabetes mellitus research, numerous investigators used X-rays or viruses to induce insulinomas, in vitro transformation, derivation of cells from transgenic mice or even non-islet cells to produce immortalised beta cell lines. The most widely used insulin-secreting cell lines are RIN, HIT, MIN, INS-1 and TC cells. These cells produce insulin and small amounts of glucagon and somatostatin. Some of them are only poorly responsive to glucose, others respond to glucose well, but their concentration-dependence curve is markedly shifted to higher sensitivity. Despite problems associated with beta cell cultures, these cell lines have provided some valuable information about physiological processes. However, an urgent need to establish a "normal" beta cell line of human or pig origin remains.
Insights
Developing functional insulin-secreting beta cell lines is challenging. Current cell lines, while useful, have limitations in glucose regulation, highlighting the need for improved human or pig beta cell models for diabetes research.
Area of Science:
- Endocrinology
- Cell Biology
- Diabetes Mellitus Research
Background:
- Significant efforts over 30 years to create insulin-secreting beta cell lines with normal regulation have yielded limited success.
- Existing immortalized beta cell lines (e.g., RIN, HIT, MIN, INS-1, TC) face challenges with glucose responsiveness and sensitivity.
- The 3Rs principles (Replacement, Reduction, Refinement) and limited primary beta cell availability drive the search for alternative models.
Purpose of the Study:
- To review the development and limitations of existing immortalized insulin-secreting cell lines.
- To highlight the ongoing need for a "normal" beta cell line of human or pig origin.
- To discuss methods used in creating beta cell lines, including X-rays, viruses, and transgenic approaches.
Main Methods:
- Review of literature on immortalized beta cell line development.
- Analysis of characteristics of commonly used cell lines (RIN, HIT, MIN, INS-1, TC).
- Examination of induction methods: X-rays, viruses, in vitro transformation, transgenic mice, and non-islet cells.
Main Results:
- Established cell lines produce insulin, glucagon, and somatostatin but exhibit variable and often abnormal glucose regulation.
- Some cell lines show poor glucose responsiveness, while others are overly sensitive.
- Despite limitations, these cell lines have contributed valuable insights into beta cell physiology.
Conclusions:
- Current immortalized beta cell lines have significant drawbacks in mimicking physiological glucose-regulated insulin secretion.
- There is an unmet need for developing "normal" beta cell lines from human or pig sources.
- Advancements in beta cell line development are crucial for future diabetes mellitus research.
