Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance

H. Kindmark, M. Köhler, P. Arkhammar, S. Efendic, O. Larsson, S. Linder, T. Nilsson, P. O. Berggren

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Plasma insulin levels in healthy subjects oscillate and non-insulin-dependent diabetic patients display an irregular pattern of such oscillations. Since an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in the pancreatic beta cell is the major stimulus for insulin release, this study was undertaken to investigate the dynamics of electrical activity, [Ca2+]i-changes and insulin release, in stimulated islets from subjects of varying glucose tolerance. In four patients it was possible to investigate more than one of these three parameters. Stimulation of pancreatic islets with glucose and tolbutamide sometimes resulted in the appearance of oscillations in [Ca2+]i, lasting 2-3 min. Such oscillations were observed even in some islets from patients with impaired glucose tolerance. In one islet from a diabetic patient there was no response to glucose, whereas that islet displayed [Ca2+]i-oscillations in response to tolbutamide, suggesting that sulphonylurea treatment can mimic the complex pattern of glucose-induced [Ca2+]i-oscillations. We also, for the first time, made patch-clamp recordings of membrane currents in beta-cells in situ in the islet. Stimulation with glucose and tolbutamide resulted in depolarization and appearance of action potentials. The islet preparations responded to stimulation with a number of different secretagogues with release of insulin. The present study shows that human islets can respond to stimulation with glucose and sulphonylurea with oscillations in [Ca2+]i, which is the signal probably underlying the oscillations in plasma insulin levels observed in healthy subjects. Interestingly, even subjects with impaired glucose tolerance had islets that responded with oscillations in [Ca2+]i upon glucose stimulation, although it is not known to what extent the response of these islets was representative of most islets in these patients.

Original languageEnglish
Pages (from-to)1121-1131
Number of pages11
JournalDiabetologia
Volume37
Issue number11
DOIs
StatePublished - Nov 1 1994
Externally publishedYes

Fingerprint

Glucose Intolerance
Islets of Langerhans
Calcium
Glucose
Tolbutamide
Insulin
Healthy Volunteers
Insulin-Secreting Cells
Action Potentials
Membranes

Keywords

  • [Ca]-oscillations
  • glucose
  • insulin secretion
  • Islets of Langerhans
  • tolbutamide

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kindmark, H., Köhler, M., Arkhammar, P., Efendic, S., Larsson, O., Linder, S., ... Berggren, P. O. (1994). Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance. Diabetologia, 37(11), 1121-1131. https://doi.org/10.1007/BF00418376

Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance. / Kindmark, H.; Köhler, M.; Arkhammar, P.; Efendic, S.; Larsson, O.; Linder, S.; Nilsson, T.; Berggren, P. O.

In: Diabetologia, Vol. 37, No. 11, 01.11.1994, p. 1121-1131.

Research output: Contribution to journalArticle

Kindmark, H, Köhler, M, Arkhammar, P, Efendic, S, Larsson, O, Linder, S, Nilsson, T & Berggren, PO 1994, 'Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance', Diabetologia, vol. 37, no. 11, pp. 1121-1131. https://doi.org/10.1007/BF00418376
Kindmark, H. ; Köhler, M. ; Arkhammar, P. ; Efendic, S. ; Larsson, O. ; Linder, S. ; Nilsson, T. ; Berggren, P. O. / Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance. In: Diabetologia. 1994 ; Vol. 37, No. 11. pp. 1121-1131.
@article{087d78eecf3045bc8d0a91c253c8fd37,
title = "Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance",
abstract = "Plasma insulin levels in healthy subjects oscillate and non-insulin-dependent diabetic patients display an irregular pattern of such oscillations. Since an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in the pancreatic beta cell is the major stimulus for insulin release, this study was undertaken to investigate the dynamics of electrical activity, [Ca2+]i-changes and insulin release, in stimulated islets from subjects of varying glucose tolerance. In four patients it was possible to investigate more than one of these three parameters. Stimulation of pancreatic islets with glucose and tolbutamide sometimes resulted in the appearance of oscillations in [Ca2+]i, lasting 2-3 min. Such oscillations were observed even in some islets from patients with impaired glucose tolerance. In one islet from a diabetic patient there was no response to glucose, whereas that islet displayed [Ca2+]i-oscillations in response to tolbutamide, suggesting that sulphonylurea treatment can mimic the complex pattern of glucose-induced [Ca2+]i-oscillations. We also, for the first time, made patch-clamp recordings of membrane currents in beta-cells in situ in the islet. Stimulation with glucose and tolbutamide resulted in depolarization and appearance of action potentials. The islet preparations responded to stimulation with a number of different secretagogues with release of insulin. The present study shows that human islets can respond to stimulation with glucose and sulphonylurea with oscillations in [Ca2+]i, which is the signal probably underlying the oscillations in plasma insulin levels observed in healthy subjects. Interestingly, even subjects with impaired glucose tolerance had islets that responded with oscillations in [Ca2+]i upon glucose stimulation, although it is not known to what extent the response of these islets was representative of most islets in these patients.",
keywords = "[Ca]-oscillations, glucose, insulin secretion, Islets of Langerhans, tolbutamide",
author = "H. Kindmark and M. K{\"o}hler and P. Arkhammar and S. Efendic and O. Larsson and S. Linder and T. Nilsson and Berggren, {P. O.}",
year = "1994",
month = "11",
day = "1",
doi = "10.1007/BF00418376",
language = "English",
volume = "37",
pages = "1121--1131",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "11",

}

TY - JOUR

T1 - Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance

AU - Kindmark, H.

AU - Köhler, M.

AU - Arkhammar, P.

AU - Efendic, S.

AU - Larsson, O.

AU - Linder, S.

AU - Nilsson, T.

AU - Berggren, P. O.

PY - 1994/11/1

Y1 - 1994/11/1

N2 - Plasma insulin levels in healthy subjects oscillate and non-insulin-dependent diabetic patients display an irregular pattern of such oscillations. Since an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in the pancreatic beta cell is the major stimulus for insulin release, this study was undertaken to investigate the dynamics of electrical activity, [Ca2+]i-changes and insulin release, in stimulated islets from subjects of varying glucose tolerance. In four patients it was possible to investigate more than one of these three parameters. Stimulation of pancreatic islets with glucose and tolbutamide sometimes resulted in the appearance of oscillations in [Ca2+]i, lasting 2-3 min. Such oscillations were observed even in some islets from patients with impaired glucose tolerance. In one islet from a diabetic patient there was no response to glucose, whereas that islet displayed [Ca2+]i-oscillations in response to tolbutamide, suggesting that sulphonylurea treatment can mimic the complex pattern of glucose-induced [Ca2+]i-oscillations. We also, for the first time, made patch-clamp recordings of membrane currents in beta-cells in situ in the islet. Stimulation with glucose and tolbutamide resulted in depolarization and appearance of action potentials. The islet preparations responded to stimulation with a number of different secretagogues with release of insulin. The present study shows that human islets can respond to stimulation with glucose and sulphonylurea with oscillations in [Ca2+]i, which is the signal probably underlying the oscillations in plasma insulin levels observed in healthy subjects. Interestingly, even subjects with impaired glucose tolerance had islets that responded with oscillations in [Ca2+]i upon glucose stimulation, although it is not known to what extent the response of these islets was representative of most islets in these patients.

AB - Plasma insulin levels in healthy subjects oscillate and non-insulin-dependent diabetic patients display an irregular pattern of such oscillations. Since an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in the pancreatic beta cell is the major stimulus for insulin release, this study was undertaken to investigate the dynamics of electrical activity, [Ca2+]i-changes and insulin release, in stimulated islets from subjects of varying glucose tolerance. In four patients it was possible to investigate more than one of these three parameters. Stimulation of pancreatic islets with glucose and tolbutamide sometimes resulted in the appearance of oscillations in [Ca2+]i, lasting 2-3 min. Such oscillations were observed even in some islets from patients with impaired glucose tolerance. In one islet from a diabetic patient there was no response to glucose, whereas that islet displayed [Ca2+]i-oscillations in response to tolbutamide, suggesting that sulphonylurea treatment can mimic the complex pattern of glucose-induced [Ca2+]i-oscillations. We also, for the first time, made patch-clamp recordings of membrane currents in beta-cells in situ in the islet. Stimulation with glucose and tolbutamide resulted in depolarization and appearance of action potentials. The islet preparations responded to stimulation with a number of different secretagogues with release of insulin. The present study shows that human islets can respond to stimulation with glucose and sulphonylurea with oscillations in [Ca2+]i, which is the signal probably underlying the oscillations in plasma insulin levels observed in healthy subjects. Interestingly, even subjects with impaired glucose tolerance had islets that responded with oscillations in [Ca2+]i upon glucose stimulation, although it is not known to what extent the response of these islets was representative of most islets in these patients.

KW - [Ca]-oscillations

KW - glucose

KW - insulin secretion

KW - Islets of Langerhans

KW - tolbutamide

UR - http://www.scopus.com/inward/record.url?scp=0028036509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028036509&partnerID=8YFLogxK

U2 - 10.1007/BF00418376

DO - 10.1007/BF00418376

M3 - Article

C2 - 7867884

AN - SCOPUS:0028036509

VL - 37

SP - 1121

EP - 1131

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 11

ER -