Paradoxical stimulation of glucagon secretion by high glucose concentrations
Salehi, S Albert LU
; Vieira, Elaine
and Gylfe, Erik
(2006)
In Diabetes
55(8).
p.2318-2323
- Abstract
- Hypersecretion of glucagon contributes to the dysregulation of glucose homeostasis in diabetes. To clarify the underlying mechanism, glucose-regulated glucagon secretion was studied in mouse pancreatic islets and clonal hamster In-R1-G9 glucagon-releasing cells. Apart from the well-known inhibition of secretion with maximal effect around 7 mmol/l glucose, we discovered that mouse islets showed paradoxical stimulation of glucagon release at 25-30 mmol/l and In-R1-G9 cells at 12-20 mmol/l sugar. Whereas glucagon secretion in the absence of glucose was inhibited by hyperpolarization with diazoxide, this agent tended to further enhance secretion stimulated by high concentrations of the sugar. Because U-shaped dose-response relationships for... (More)
- Hypersecretion of glucagon contributes to the dysregulation of glucose homeostasis in diabetes. To clarify the underlying mechanism, glucose-regulated glucagon secretion was studied in mouse pancreatic islets and clonal hamster In-R1-G9 glucagon-releasing cells. Apart from the well-known inhibition of secretion with maximal effect around 7 mmol/l glucose, we discovered that mouse islets showed paradoxical stimulation of glucagon release at 25-30 mmol/l and In-R1-G9 cells at 12-20 mmol/l sugar. Whereas glucagon secretion in the absence of glucose was inhibited by hyperpolarization with diazoxide, this agent tended to further enhance secretion stimulated by high concentrations of the sugar. Because U-shaped dose-response relationships for glucose-regulated glucagon secretion were observed in normal islets and in clonal glucagon-releasing cells, both the inhibitory and stimulatory components probably reflect direct effects on the a-cells. Studies of isolated mouse a-cells indicated that glucose inhibited glucagon secretion by lowering the cytoplasmic Ca2+ concentration. However, stimulation of glucagon release by high glucose concentrations did not require elevation of Ca2+, indicating involvement of novel mechanisms in glucose regulation of glucagon secretion. A U-shaped dose-response relationship for glucose-regulated glucagon secretion may explain why diabetic patients with pronounced hyperglycemia display paradoxical hyperglucagonemia. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/686336
- author
- Salehi, S Albert
LU
; Vieira, Elaine
and Gylfe, Erik
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 55
- issue
- 8
- pages
- 2318 - 2323
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- wos:000239468300019
- pmid:16873696
- scopus:33749347851
- pmid:16873696
- ISSN
- 1939-327X
- DOI
- 10.2337/db06-0080
- language
- English
- LU publication?
- yes
- id
- e38e7b72-ed4a-4a9b-b972-ad4ba7daf261 (old id 686336)
- date added to LUP
- 2016-04-01 15:59:30
- date last changed
- 2022-03-30 04:44:02
@article{e38e7b72-ed4a-4a9b-b972-ad4ba7daf261,
abstract = {{Hypersecretion of glucagon contributes to the dysregulation of glucose homeostasis in diabetes. To clarify the underlying mechanism, glucose-regulated glucagon secretion was studied in mouse pancreatic islets and clonal hamster In-R1-G9 glucagon-releasing cells. Apart from the well-known inhibition of secretion with maximal effect around 7 mmol/l glucose, we discovered that mouse islets showed paradoxical stimulation of glucagon release at 25-30 mmol/l and In-R1-G9 cells at 12-20 mmol/l sugar. Whereas glucagon secretion in the absence of glucose was inhibited by hyperpolarization with diazoxide, this agent tended to further enhance secretion stimulated by high concentrations of the sugar. Because U-shaped dose-response relationships for glucose-regulated glucagon secretion were observed in normal islets and in clonal glucagon-releasing cells, both the inhibitory and stimulatory components probably reflect direct effects on the a-cells. Studies of isolated mouse a-cells indicated that glucose inhibited glucagon secretion by lowering the cytoplasmic Ca2+ concentration. However, stimulation of glucagon release by high glucose concentrations did not require elevation of Ca2+, indicating involvement of novel mechanisms in glucose regulation of glucagon secretion. A U-shaped dose-response relationship for glucose-regulated glucagon secretion may explain why diabetic patients with pronounced hyperglycemia display paradoxical hyperglucagonemia.}},
author = {{Salehi, S Albert and Vieira, Elaine and Gylfe, Erik}},
issn = {{1939-327X}},
language = {{eng}},
number = {{8}},
pages = {{2318--2323}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Paradoxical stimulation of glucagon secretion by high glucose concentrations}},
url = {{http://dx.doi.org/10.2337/db06-0080}},
doi = {{10.2337/db06-0080}},
volume = {{55}},
year = {{2006}},
}