A Controversy Regarding the Identity of the Enzyme That Mediates Glucagon-Like Peptide 1 Synthesis in Human Alpha Cells.

Bibliographic Details
Title: A Controversy Regarding the Identity of the Enzyme That Mediates Glucagon-Like Peptide 1 Synthesis in Human Alpha Cells.
Authors: Teitelman G; Downstate Health Sciences University, Brooklyn, New York (GT).
Source: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society [J Histochem Cytochem] 2024 Aug-Sep; Vol. 72 (8-9), pp. 545-550. Date of Electronic Publication: 2024 Sep 09.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: SAGE Publications Country of Publication: United States NLM ID: 9815334 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1551-5044 (Electronic) Linking ISSN: 00221554 NLM ISO Abbreviation: J Histochem Cytochem Subsets: MEDLINE
Imprint Name(s): Publication: <2011->: Thousand Oaks, CA : SAGE Publications
Original Publication: Baltimore : Williams & Wilkins Co., c1953-
MeSH Terms: Glucagon-Like Peptide 1*/metabolism , Glucagon-Secreting Cells*/metabolism , Proprotein Convertase 1*/metabolism , Proprotein Convertase 1*/genetics , Proprotein Convertase 2*/metabolism , Proprotein Convertase 2*/genetics, Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 1/pathology ; Glucagon/metabolism ; Humans ; Adult ; Male ; Middle Aged ; Female
Abstract: Processing of proglucagon into glucagon-like peptide-1 (GLP-1) and GLP-2 in intestinal L cells is mediated by the prohormone convertase 1/3 (PC1/3) while PC2 is responsible for the synthesis of glucagon in pancreatic alpha cells. While GLP-1 is also produced by alpha cells, the identity of the convertase involved in its synthesis is still unsettled. It also remains to be determined whether all alpha cells produce the incretin. The aims of this study were first, to elucidate the identity of the proconvertase responsible for GLP-1 production in human alpha cells, and second, to ascertain whether the number of glucagon cells expressing GLP-1 increase during diabetes. To answer these questions, sections of pancreas from donors' non-diabetic controls, type 1 and type 2 diabetes were processed for double-labelled immunostaining of glucagon and GLP-1 and of each hormone and either PC1 or PC2. Stained sections were examined by confocal microscopy. It was found that all alpha cells of islets from those three groups expressed GLP-1 and PC2 but not PC1/3. This observation supports the view that PC2 is the convertase involved in GLP-1 synthesis in all human glucagon cells and suggests that the regulation of its activity may have important clinical application in diabetes.
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Contributed Indexing: Keywords: Diabetes Mellitus; Glucagon-Like peptide-1; Proprotein convertase-2
Substance Nomenclature: 89750-14-1 (Glucagon-Like Peptide 1)
EC 3.4.21.93 (Proprotein Convertase 1)
EC 3.4.21.94 (Proprotein Convertase 2)
9007-92-5 (Glucagon)
Entry Date(s): Date Created: 20240909 Date Completed: 20240923 Latest Revision: 20250910
Update Code: 20260130
PubMed Central ID: PMC11425746
DOI: 10.1369/00221554241274879
PMID: 39248433
Database: MEDLINE
Description
ISSN:1551-5044
DOI:10.1369/00221554241274879