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Published on: November 3, 2023
A role for SPARC in the moderation of human insulin secretion
Lorna W Harries1, Laura J McCulloch, Janet E Holley
1Institute of Biomedical and Clinical Sciences, Exeter Medical School, University of Exeter, Exeter, United Kingdom. L.W.Harries@exeter.ac.uk
Aims/Hypothesis:
We have previously shown the implication of the multifunctional protein SPARC (Secreted protein acidic and rich in cysteine)/osteonectin in insulin resistance but potential effects on beta-cell function have not been assessed. We therefore aimed to characterise the effect of SPARC on beta-cell function and features of diabetes.
Methods:
We measured SPARC expression by qRT-PCR in human primary pancreatic islets, adipose tissue, liver and muscle. We then examined the relation of SPARC with glucose stimulated insulin secretion (GSIS) in primary human islets and the effect of SPARC overexpression on GSIS in beta cell lines.
Results:
SPARC was expressed at measurable levels in human islets, adipose tissue, liver and skeletal muscle, and demonstrated reduced expression in primary islets from subjects with diabetes compared with controls (p< = 0.05). SPARC levels were positively correlated with GSIS in islets from control donors (p< = 0.01). Overexpression of SPARC in cultured beta-cells resulted in a 2.4-fold increase in insulin secretion in high glucose conditions (p< = 0.01).
Conclusions:
Our data suggest that levels of SPARC are reduced in islets from donors with diabetes and that it has a role in insulin secretion, an effect which appears independent of SPARC's modulation of obesity-induced insulin resistance in adipose tissue.
Insights
Secreted protein acidic and rich in cysteine (SPARC) levels are lower in diabetic islets and SPARC enhances glucose-stimulated insulin secretion, suggesting a role in diabetes regulation.
Area of Science:
- Endocrinology
- Metabolic Research
- Molecular Biology
Background:
- The multifunctional protein SPARC (Secreted protein acidic and rich in cysteine)/osteonectin is implicated in insulin resistance.
- The specific impact of SPARC on pancreatic beta-cell function remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of SPARC in pancreatic beta-cell function.
- To determine the effect of SPARC on diabetes-related features.
Main Methods:
- SPARC expression was quantified using qRT-PCR in human islets, adipose tissue, liver, and muscle.
- The correlation between SPARC levels and glucose-stimulated insulin secretion (GSIS) was assessed in human islets.
- The impact of SPARC overexpression on GSIS was evaluated in beta-cell lines.
Main Results:
- SPARC was expressed in human islets, adipose tissue, liver, and skeletal muscle.
- Reduced SPARC expression was observed in islets from individuals with diabetes compared to controls.
- SPARC levels positively correlated with GSIS in control islets.
- Overexpression of SPARC significantly increased insulin secretion under high glucose conditions in beta-cells.
Conclusions:
- SPARC expression is diminished in pancreatic islets of individuals with diabetes.
- SPARC plays a role in regulating insulin secretion.
- The observed effect of SPARC on insulin secretion appears independent of its influence on obesity-induced insulin resistance.
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