The pancreatic beta-cell recognition of insulin secretagogues. Effects of calcium and sodium on glucose metabolism and insulin release
Hellman, B ; Idahl, L A ; Lernmark, A LU
; Sehlin, J
and Täljedal, I B
(1974)
In The Biochemical journal
138(1).
p.33-45
- Abstract
The transport and oxidation of glucose, the content of fructose 1,6-diphosphate, and the release of insulin were studied in microdissected pancreatic islets of ob/ob mice incubated in Krebs-Ringer bicarbonate medium. Under control conditions glucose oxidation and insulin release showed a similar dependence on glucose concentration with the steepest slope in the range 5-12mm. The omission of Ca(2+), or the substitution of choline ions for Na(+), or the addition of diazoxide had little if any effect on glucose transport. However, Ca(2+) or Na(+) deficiency as well as diazoxide (7-chloro-3-methyl-1,2,4-benzothiadiazine 1,1-dioxide) or ouabain partially inhibited glucose oxidation. These alterations of medium composition also increased the... (More)
The transport and oxidation of glucose, the content of fructose 1,6-diphosphate, and the release of insulin were studied in microdissected pancreatic islets of ob/ob mice incubated in Krebs-Ringer bicarbonate medium. Under control conditions glucose oxidation and insulin release showed a similar dependence on glucose concentration with the steepest slope in the range 5-12mm. The omission of Ca(2+), or the substitution of choline ions for Na(+), or the addition of diazoxide had little if any effect on glucose transport. However, Ca(2+) or Na(+) deficiency as well as diazoxide (7-chloro-3-methyl-1,2,4-benzothiadiazine 1,1-dioxide) or ouabain partially inhibited glucose oxidation. These alterations of medium composition also increased the islet content of fructose 1,6-diphosphate, as did the addition of adrenaline. Phentolamine [2-N-(3-hydroxyphenyl)-p-toluidinomethyl-2-imidazoline] counteracted the effects of adrenaline and Ca(2+) deficiency on islet fructose 1,6-diphosphate. After equilibration in Na(+)-deficient medium, the islets exhibited an increase in basal insulin release whereas the secretory response to glucose was inhibited. The inhibitory effects of Na(+) deficiency on the secretory responses to different concentrations of glucose correlated with those on (14)CO(2) production. When islets were incubated with 17mm-glucose, the sudden replacement of Na(+) by choline ions resulted in a marked but transient stimulation of insulin release that was not accompanied by a demonstrable increase of glucose oxidation. Galactose and 3-O-methylglucose had no effect on glucose oxidation or on insulin release. The results are consistent with a metabolic model of the beta-cell recognition of glucose as insulin secretagogue and with the assumption that Ca(2+) or Na(+) deficiency, or the addition of adrenaline or diazoxide, inhibit insulin release at some step distal to stimulus recognition. In addition the results suggest that these conditions create a partial metabolic block of glycolysis in the beta-cells. Hence the interrelationship between the processes of stimulus recognition and insulin discharge may involve a positive feedback of secretion on glucose metabolism.
(Less)
- author
- Hellman, B
; Idahl, L A
; Lernmark, A
LU
; Sehlin, J
and Täljedal, I B
- publishing date
- 1974
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Biological Transport, Calcium/pharmacology, Carbon Radioisotopes, Choline/pharmacology, Diazoxide/pharmacology, Epinephrine/pharmacology, Fructosephosphates/metabolism, Galactose/pharmacology, Glucose/metabolism, Insulin/metabolism, Insulin Secretion, Iodine Radioisotopes, Islets of Langerhans/drug effects, Kinetics, Methanol, Mice, Ouabain/pharmacology, Phentolamine/pharmacology, Sodium/pharmacology, Time Factors, Tritium
- in
- The Biochemical journal
- volume
- 138
- issue
- 1
- pages
- 33 - 45
- publisher
- Portland Press
- external identifiers
-
- pmid:4601168
- scopus:0015975778
- ISSN
- 0264-6021
- DOI
- 10.1042/bj1380033
- language
- English
- LU publication?
- no
- id
- 67d6a9e3-adfc-4cd5-9cf4-8dffa6b69de3
- date added to LUP
- 2021-09-15 16:28:12
- date last changed
- 2024-03-13 08:01:34
@article{67d6a9e3-adfc-4cd5-9cf4-8dffa6b69de3,
abstract = {{<p>The transport and oxidation of glucose, the content of fructose 1,6-diphosphate, and the release of insulin were studied in microdissected pancreatic islets of ob/ob mice incubated in Krebs-Ringer bicarbonate medium. Under control conditions glucose oxidation and insulin release showed a similar dependence on glucose concentration with the steepest slope in the range 5-12mm. The omission of Ca(2+), or the substitution of choline ions for Na(+), or the addition of diazoxide had little if any effect on glucose transport. However, Ca(2+) or Na(+) deficiency as well as diazoxide (7-chloro-3-methyl-1,2,4-benzothiadiazine 1,1-dioxide) or ouabain partially inhibited glucose oxidation. These alterations of medium composition also increased the islet content of fructose 1,6-diphosphate, as did the addition of adrenaline. Phentolamine [2-N-(3-hydroxyphenyl)-p-toluidinomethyl-2-imidazoline] counteracted the effects of adrenaline and Ca(2+) deficiency on islet fructose 1,6-diphosphate. After equilibration in Na(+)-deficient medium, the islets exhibited an increase in basal insulin release whereas the secretory response to glucose was inhibited. The inhibitory effects of Na(+) deficiency on the secretory responses to different concentrations of glucose correlated with those on (14)CO(2) production. When islets were incubated with 17mm-glucose, the sudden replacement of Na(+) by choline ions resulted in a marked but transient stimulation of insulin release that was not accompanied by a demonstrable increase of glucose oxidation. Galactose and 3-O-methylglucose had no effect on glucose oxidation or on insulin release. The results are consistent with a metabolic model of the beta-cell recognition of glucose as insulin secretagogue and with the assumption that Ca(2+) or Na(+) deficiency, or the addition of adrenaline or diazoxide, inhibit insulin release at some step distal to stimulus recognition. In addition the results suggest that these conditions create a partial metabolic block of glycolysis in the beta-cells. Hence the interrelationship between the processes of stimulus recognition and insulin discharge may involve a positive feedback of secretion on glucose metabolism.</p>}},
author = {{Hellman, B and Idahl, L A and Lernmark, A and Sehlin, J and Täljedal, I B}},
issn = {{0264-6021}},
keywords = {{Animals; Biological Transport; Calcium/pharmacology; Carbon Radioisotopes; Choline/pharmacology; Diazoxide/pharmacology; Epinephrine/pharmacology; Fructosephosphates/metabolism; Galactose/pharmacology; Glucose/metabolism; Insulin/metabolism; Insulin Secretion; Iodine Radioisotopes; Islets of Langerhans/drug effects; Kinetics; Methanol; Mice; Ouabain/pharmacology; Phentolamine/pharmacology; Sodium/pharmacology; Time Factors; Tritium}},
language = {{eng}},
number = {{1}},
pages = {{33--45}},
publisher = {{Portland Press}},
series = {{The Biochemical journal}},
title = {{The pancreatic beta-cell recognition of insulin secretagogues. Effects of calcium and sodium on glucose metabolism and insulin release}},
url = {{http://dx.doi.org/10.1042/bj1380033}},
doi = {{10.1042/bj1380033}},
volume = {{138}},
year = {{1974}},
}