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Updated: May 30, 2026
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A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
Published on: July 16, 2016
Pleiotropic effects of GIP on islet function involve osteopontin
Valeriya Lyssenko1, Lena Eliasson, Olga Kotova
1Diabetes and Endocrinology, Department of Clinical Sciences, University Hospital Malmö, Lund University, Malmö, Sweden. valeriya.lyssenko@med.lu.se
Diabetes
|August 4, 2011
Summary
The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) and its receptor (GIPR) play protective roles in pancreatic beta-cells. GIP signaling, linked to osteopontin, enhances beta-cell survival and proliferation, potentially preventing type 2 diabetes.
Area of Science:
- Endocrinology
- Metabolic Research
- Genetics
Background:
- The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) is known to enhance pancreatic beta-cell function, including insulin secretion and proliferation.
- Genome-wide association studies have identified associations between the GIP receptor (GIPR) locus and postprandial insulin levels.
- Understanding the precise mechanisms behind GIP's protective effects on islet function is crucial for metabolic disease research.
Purpose of the Study:
- To investigate the mechanisms underlying the protective effects of GIP on pancreatic islet function.
- To explore the association of a specific GIPR genetic variant (rs10423928) with metabolic phenotypes and insulin secretion.
- To elucidate the role of GIP in beta-cell viability, proliferation, and its potential link with osteopontin (OPN).
Main Methods:
- Analysis of GIPR rs10423928 associations with metabolic and anthropometric data in large cohorts of non-diabetic and type 2 diabetic individuals.
- In vivo and in vitro assessment of insulin secretion in response to GIP.
- Measurement of GIPR, osteopontin (OPN) gene and protein expression, beta-cell viability, and proliferation in human islets.
Main Results:
- The GIPR rs10423928 A allele was linked to reduced insulin secretion, lower BMI, and decreased lean body mass, which largely offset the increased type 2 diabetes risk.
- GIPR mRNA expression was diminished in islets from A allele carriers and type 2 diabetic patients.
- GIP stimulated OPN expression, and both GIP and OPN demonstrated anti-apoptotic effects, with OPN promoting beta-cell proliferation.
Conclusions:
- GIP exhibits beta-cell proliferative and anti-apoptotic functions beyond its incretin role.
- The newly identified link between GIP and OPN offers novel insights into GIP's role in maintaining functional beta-cell mass in humans.
- These findings highlight potential therapeutic targets for preserving beta-cell function in metabolic diseases.
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