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Palmitate-Induced Insulin Hypersecretion and Later Secretory Decline Associated with Changes in Protein Expression
Karlfried Groebe1, Jing Cen2, Domitille Schvartz3
1Pivot Biomed Science GmbH , 54296 Trier , Germany.
Journal of Proteome Research
|September 6, 2018
Summary
High palmitate levels in obese children initially increase insulin secretion but later impair islet cell function. This study reveals biological events linked to these changes, potentially informing new treatments for obesity-related type 2 diabetes.
Area of Science:
- Metabolic research
- Endocrinology
- Cell biology
Background:
- Obese children with high free fatty acid palmitate show varied insulin responses, from hypersecretion to insufficiency.
- Palmitate exposure in human islets initially causes hypersecretion, followed by reduced insulin secretion.
Purpose of the Study:
- To identify islet-related biological events behind altered insulin secretion in obese children exposed to palmitate.
- To understand the mechanisms of insulin hypersecretion and subsequent decline using an islet model.
Main Methods:
- Analyzed protein expression in human islets exposed to elevated palmitate for 2 and 7 days.
- Utilized liquid chromatography-tandem mass spectrometry for protein profiling and identified differentially expressed proteins (DEPs).
- Applied improved statistical analysis for DEPs.
Main Results:
- Identified 115 differentially expressed proteins (DEPs) in islets after palmitate exposure.
- Found DEPs, including sorcin, linked to increased glucose-stimulated insulin secretion after 2 days.
- Observed impaired islet function after 7 days, associated with altered protein degradation, autophagy, redox balance, and insulin processing.
Conclusions:
- Specific biological events in islets correlate with palmitate-induced changes in insulin secretion.
- Findings may lead to novel therapeutic strategies for normalizing insulin levels in obese children.
- Potential to reduce or prevent obesity-related type 2 diabetes mellitus.
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