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Insulin-secreting beta-cell dysfunction induced by human lipoproteins
Marc-Estienne Roehrich1, Vincent Mooser, Vincent Lenain
1Department of Internal Medicine and Institute of Cellular Biology and Morphology, University Hospital, Lausanne 1011, Switzerland.
The Journal of Biological Chemistry
|February 21, 2003
Summary
Lipoproteins like LDL and VLDL harm insulin-producing beta-cells, increasing apoptosis. However, high-density lipoprotein (HDL) protects these vital cells, suggesting a role in type 2 diabetes development.
Area of Science:
- Endocrinology
- Cell Biology
- Metabolic Diseases
Background:
- Diabetes mellitus is linked to altered plasma lipoprotein levels.
- Lipoproteins may influence the function and survival of pancreatic beta-cells, which secrete insulin.
Purpose of the Study:
- To investigate the impact of lipoproteins on beta-cell function and survival.
- To determine the mechanisms by which lipoproteins affect beta-cells.
Main Methods:
- Detection of lipoprotein receptors on beta-cells.
- Internalization studies using fluorescent low-density lipoprotein (LDL) and high-density lipoprotein (HDL).
- Assessment of insulin mRNA, beta-cell proliferation, and apoptosis in response to very low-density lipoprotein (VLDL) and LDL, including studies in LDL receptor-deficient mice.
Main Results:
- VLDL and LDL reduced insulin mRNA, beta-cell proliferation, and increased apoptosis in a dose-dependent manner.
- LDL receptor-deficient mice showed reduced LDL uptake and partial resistance to LDL-induced apoptosis.
- VLDL-induced apoptosis involved caspase-3 and reduced c-Jun N-terminal kinase-interacting protein-1; HDL antagonized these effects, partly via Akt/protein kinase B activation.
Conclusions:
- Human lipoproteins critically regulate beta-cell survival.
- Lipoprotein dysregulation may contribute to beta-cell dysfunction in type 2 diabetes.