Preproglucagon Products and Their Respective Roles Regulating Insulin Secretion

Historically, intracellular function and metabolic adaptation within the α-cell has been understudied, with most of the attention being placed on the insulin-producing β-cells due to their role in the pathophysiology of type 2 diabetes mellitus. However, there is a growing interest in understanding...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2021-10, Vol.162 (10), p.1
Main Authors: Bethea, Maigen, Bozadjieva-Kramer, Nadejda, Sandoval, Darleen A
Format: Article
Language:English
Subjects:
Animals
Beta cells
Blood Glucose - analysis
Cells
Dextrose
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - metabolism
Endocrinology
Glucagon
Glucagon - metabolism
Glucagon-like peptide 1
Glucagon-Like Peptide 1 - metabolism
Glucagon-Secreting Cells - metabolism
Glucose
Glucose - metabolism
Homeostasis
Humans
Insulin
Insulin - metabolism
Insulin Secretion
Insulin-Secreting Cells - metabolism
Liraglutide
Metabolism
Mice
Mini-Review
Pancreas - metabolism
Paracrine signalling
Proglucagon - metabolism
Secretion
Type 2 diabetes
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Summary:Historically, intracellular function and metabolic adaptation within the α-cell has been understudied, with most of the attention being placed on the insulin-producing β-cells due to their role in the pathophysiology of type 2 diabetes mellitus. However, there is a growing interest in understanding the function of other endocrine cell types within the islet and their paracrine role in regulating insulin secretion. For example, there is greater appreciation for α-cell products and their contributions to overall glucose homeostasis. Several recent studies have addressed a paracrine role for α-cell-derived glucagon-like peptide-1 (GLP-1) in regulating glucose homeostasis and responses to metabolic stress. Further, other studies have demonstrated the ability of glucagon to impact insulin secretion by acting through the GLP-1 receptor. These studies challenge the central dogma surrounding α-cell biology describing glucagon's primary role in glucose counterregulation to one where glucagon is critical in regulating both hyper- and hypoglycemic responses. Herein, this review will update the current understanding of the role of glucagon and α-cell-derived GLP-1, placing emphasis on their roles in regulating glucose homeostasis, insulin secretion, and β-cell mass.
ISSN:0013-7227
1945-7170
DOI:10.1210/endocr/bqab150