Back to Search
Start Over
STEAP4 expression in human islets is associated with differences in body mass index, sex, HbA1c, and inflammation
- Source :
- Endocrine. 56:528-537
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- STEAP4 (six-transmembrane epithelial antigen of the prostate 4) is a metalloreductase that has been shown previously to protect cells from inflammatory damage. Genetic variants in STEAP4 have been associated with numerous metabolic disorders related to obesity, including putative defects in the acute insulin response to glucose in type 2 diabetes.We examined whether obesity and/or type 2 diabetes altered STEAP4 expression in human pancreatic islets.Human islets were isolated from deceased donors at two medical centers and processed for quantitative polymerase chain reaction. Organ donors were selected by status as non-diabetic or having type 2 diabetes. Site 1 (Edmonton): N = 13 type 2 diabetes donors (7M, 6F), N = 20 non-diabetic donors (7M, 13F). Site 2 (Virginia): N = 6 type 2 diabetes donors (6F), N = 6 non-diabetic donors (3M, 3F).STEAP4 showed reduced islet expression with increasing body mass index among all donors (P 0.10) and non-diabetic donors (P 0.05) from Site 1; STEAP4 showed reduced islet expression among type 2 diabetes donors with increasing hemoglobin A1c. Islet STEAP4 expression was also marginally higher in female donors (P 0.10). Among type 2 diabetes donors from Site 2, islet insulin expression was reduced, STEAP4 expression was increased, and white blood cell counts were increased compared to non-diabetic donors. Islets from non-diabetic donors that were exposed overnight to 5 ng/ml IL-1β displayed increased STEAP4 expression, consistent with STEAP4 upregulation by inflammatory signaling.These findings suggest that increased STEAP4 mRNA expression is associated with inflammatory stimuli, whereas lower STEAP4 expression is associated with obesity in human islets. Given its putative protective role, downregulation of STEAP4 by chronic obesity suggests a mechanism for reduced islet protection against cellular damage.
- Subjects :
- Adult
Male
0301 basic medicine
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Inflammation
Type 2 diabetes
Biology
Article
Body Mass Index
Islets of Langerhans
03 medical and health sciences
Sex Factors
Endocrinology
Antigen
Prostate
Internal medicine
Diabetes mellitus
medicine
Humans
Obesity
Aged
Glycated Hemoglobin
geography
geography.geographical_feature_category
Membrane Proteins
Middle Aged
medicine.disease
Islet
030104 developmental biology
medicine.anatomical_structure
Diabetes Mellitus, Type 2
Immunology
Female
medicine.symptom
Oxidoreductases
Body mass index
Subjects
Details
- ISSN :
- 15590100 and 1355008X
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Endocrine
- Accession number :
- edsair.doi.dedup.....d82cd3e38d6de38066841664c149dc4d