Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudoislets.

Abstract:

:Misregulated hormone secretion from the islet of Langerhans is central to the pathophysiology of diabetes. Although insulin plays a key role in glucose regulation, the importance of glucagon is increasingly acknowledged. However, the mechanisms that regulate glucagon secretion from α-cells are still unclear. We used pseudoislets reconstituted from dispersed islet cells to study α-cells with and without various indirect effects from other islet cells. Dispersed islet cells secrete aberrant levels of glucagon and insulin at basal and elevated glucose levels. When cultured, murine islet cells reassociate to form pseudoislets, which recover normal glucose-regulated hormone secretion, and human islet cells follow a similar pattern. We created small (∼40-µm) pseudoislets using all of the islet cells or only some of the cell types, which allowed us to characterize novel aspects of regulated hormone secretion. The recovery of regulated glucagon secretion from α-cells in small pseudoislets depends upon the combined action of paracrine factors, such as insulin and somatostatin, and juxtacrine signals between EphA4/7 on α-cells and ephrins on β-cells. Although these signals modulate different pathways, both appear to be required for proper inhibition of glucagon secretion in response to glucose. This improved understanding of the modulation of glucagon secretion can provide novel therapeutic routes for the treatment of some individuals with diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Reissaus CA,Piston DW

doi

10.2337/db16-1291

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

960-969

issue

4

eissn

0012-1797

issn

1939-327X

pii

db16-1291

journal_volume

66

pub_type

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