Novel regulatory roles of small G protein GDP dissociation stimulator (smgGDS) in insulin secretion from pancreatic β-cells. Mol Cell Endocrinol 2024 Jan 15;580:112104
Date
11/28/2023Pubmed ID
38013223Pubmed Central ID
PMC10842139DOI
10.1016/j.mce.2023.112104Scopus ID
2-s2.0-85175808786 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Emerging evidence implicates novel roles for small G protein GDP dissociation stimulator (smgGDS) in G protein activation and subsequent targeting to relevant subcellular compartments for effector regulation. Given the well-established roles of small G proteins in insulin secretion, we undertook this investigation to determine the putative roles of smgGDS in insulin secretion. Immunoblotting studies revealed that both splice variants of smgGDS are expressed in human islets, rat islets and INS-1 832/13 cells. A significant inhibition (-52%) of glucose-stimulated insulin secretion (GSIS) was observed in INS-1 832/13 cells following siRNA-mediated depletion of smgGDS. In addition, insulin secretion elicited by a membrane depolarizing concentration of KCl (via increased calcium influx), forskolin (via increased cAMP generation) or IBMX (via inhibition of phosphodiesterase) was inhibited by -49%, -27%, and -28%, respectively. Subcellular distribution studies revealed no significant alterations in the abundance of smgGDS in the cytosolic and membrane fractions during the 45-min exposure of INS-1 832/13 cells to an insulinotropic concentration of glucose. Together, we present the first evidence of expression of smgGDS in human islets, rodent islets, and clonal β-cells. We also demonstrate novel regulatory roles of these proteins in insulin secretion derived from glucose metabolic events, including calcium- and cAMP-dependent signaling steps.
Author List
Gleason N, Williams CL, Kowluru AAuthor
Carol L. Williams PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Cell Line
Glucose
Guanine Nucleotide Exchange Factors
Humans
Insulin
Insulin-Secreting Cells
Islets of Langerhans
Monomeric GTP-Binding Proteins
Rats
