GC-Globulin/Vitamin D–Binding Protein Is Required for Pancreatic α-Cell Adaptation to Metabolic Stress
Year: 2022
Type: article
Abstract: GC-globulin (GC), or vitamin D-binding protein, is a multifunctional protein involved in the transport of circulating vitamin 25(OH)D and fatty acids, as well as actin scavenging. In the pancreatic islets, the gene encoding GC, GC/Gc, is highly localized to glucagon-secreting α-cells. Despite this, the role of GC in α-cell function is poorly understood. We previously showed that GC is essential for α-cell morphology, electrical activity, and glucagon secretion. We now show that loss of GC exacerbates α-cell failure during metabolic stress. High-fat diet-fed GC-/- mice have basal hyperglucagonemia, which is associated with decreased α-cell size, impaired glucagon secretion and Ca2+ fluxes, and changes in glucose-dependent F-actin remodelling. Impairments in glucagon secretion can be rescued using exogenous GC to replenish α-cell GC levels, increase glucagon granule area, and restore the F-actin cytoskeleton. Lastly, GC levels decrease in α-cells of donors with type 2 diabetes, which is associated with changes in α-cell mass, morphology, and glucagon expression. Together, these data demonstrate an important role for GC in α-cell adaptation to metabolic stress.
Source: Diabetes
DOI: 10.2337/db22-0326
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Investigating the role of immature beta cells in insulin release from the intact islet, G4751757086, All-optical deconstruction of the islet wiring patterns underlying insulin secretion in health and disease, Linking GPCR organization states with functional heterogeneity in the pancreatic islet, Exploring beta cell reprogramming by glucocorticoids, Functional and computational analyses of the regulation of glucagon secretion in health and disease
OpenAlex ID: W4310591497