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Journal article
GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
Scientific reports, v 11(1), pp 11129-11129
27 May 2021
PMID: 34045505
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Diabetes is a metabolic syndrome rooted in impaired insulin and/or glucagon secretory responses within the pancreatic islets of Langerhans (islets). Insulin secretion is primarily regulated by two key factors: glucose-mediated ATP production and G-protein coupled receptors (GPCRs) signaling. GPCR kinase 2 (GRK2), a key regulator of GPCRs, is reported to be downregulated in the pancreas of spontaneously obesogenic and diabetogenic mice (ob/ob). Moreover, recent studies have shown that GRK2 non-canonically localizes to the cardiac mitochondrion, where it can contribute to glucose metabolism. Thus, islet GRK2 may impact insulin secretion through either mechanism. Utilizing Min6 cells, a pancreatic ss -cell model, we knocked down GRK2 and measured glucose-mediated intracellular calcium responses and insulin secretion. Silencing of GRK2 attenuated calcium responses, which were rescued by pertussis toxin pre-treatment, suggesting a G alpha i/o-dependent mechanism. Pancreatic deletion of GRK2 in mice resulted in glucose intolerance with diminished insulin secretion. These differences were due to diminished insulin release rather than decreased insulin content or gross differences in islet architecture. Furthermore, a high fat diet feeding regimen exacerbated the metabolic phenotype in this model. These results suggest a new role for pancreatic islet GRK2 in glucose-mediated insulin responses that is relevant to type 2 diabetes disease progression.
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Details
- Title
- GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
- Creators
- Jonathan Snyder - Drexel UniversityAtreju Lackey - Drexel UniversityG. Schuyler Brown - Drexel UniversityMelisa Diaz - Drexel UniversityTian Yuzhen - Drexel UniversityPriscila Y. Sato - Drexel University
- Publication Details
- Scientific reports, v 11(1), pp 11129-11129
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 12
- Grant note
- 17SDG33660407 / American Heart Association Scientist Developmental Grant (PYS); American Heart Association P30 DK019525 / National Institutes of Health (NIH) Diabetes Research Center
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000658389400044
- Scopus ID
- 2-s2.0-85106934519
- Other Identifier
- 991019168281304721
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- Web of Science research areas
- Biochemistry & Molecular Biology