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Mitochondrial metabolism reveals a functional architecture in intact islets of Langerhans from normal and diabetic Psammomys obesus

Mitochondrial metabolism reveals a functional architecture in intact islets of Langerhans from normal and diabetic Psammomys obesus
Mitochondrial metabolism reveals a functional architecture in intact islets of Langerhans from normal and diabetic Psammomys obesus
The cells within the intact islet of Langerhans function as a metabolic syncytium, secreting insulin in a coordinated and oscillatory manner in response to external fuel. With increased glucose, the oscillatory amplitude is enhanced, leading to the hypothesis that cells within the islet are secreting with greater synchronization. Consequently, non-insulin-dependent diabetes mellitus (NIDDM; type 2 diabetes)-induced irregularities in insulin secretion oscillations may be attributed to decreased intercellular coordination. The purpose of the present study was to determine whether the degree of metabolic coordination within the intact islet was enhanced by increased glucose and compromised by NIDDM. Experiments were performed with isolated islets from normal and diabetic Psammomys obesus.

Using confocal microscopy and the mitochondrial potentiometric dye rhodamine 123, we measured mitochondrial membrane potential oscillations in individual cells within intact islets. When mitochondrial membrane potential was averaged from all the cells in a single islet, the resultant waveform demonstrated clear sinusoidal oscillations. Cells within islets were heterogeneous in terms of cellular synchronicity (similarity in phase and period), sinusoidal regularity, and frequency of oscillation. Cells within normal islets oscillated with greater synchronicity compared with cells within diabetic islets. The range of oscillatory frequencies was unchanged by glucose or diabetes. Cells within diabetic (but not normal) islets increased oscillatory regularity in response to glucose. These data support the hypothesis that glucose enhances metabolic coupling in normal islets and that the dampening of oscillatory insulin secretion in NIDDM may result from disrupted metabolic coupling.

0193-1849
E1090-E1099
Katzman, S.M.
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Messerli, M.A.
0d35456b-47c1-4590-81cd-12b483a422ca
Grossman, A.
da38cc00-f1e2-4507-9f1c-41cadc5d9c06
Harel, T.
9c36eaf7-8803-4759-a0eb-b81a3c4fd147
Barry, D.T.
2625f520-e7ef-4bea-bf85-01051c98ae85
Smith, P.J.S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Chenault, V.M.
2befd28b-ddba-4a8a-9fd3-022a0464b4db
Shirihai, O.S.
48b41f0e-87ba-452c-97f8-326e21ed2bcc
Katzman, S.M.
713339c7-f848-4330-b8e7-29ed4eb0c42a
Messerli, M.A.
0d35456b-47c1-4590-81cd-12b483a422ca
Grossman, A.
da38cc00-f1e2-4507-9f1c-41cadc5d9c06
Harel, T.
9c36eaf7-8803-4759-a0eb-b81a3c4fd147
Barry, D.T.
2625f520-e7ef-4bea-bf85-01051c98ae85
Smith, P.J.S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Chenault, V.M.
2befd28b-ddba-4a8a-9fd3-022a0464b4db
Shirihai, O.S.
48b41f0e-87ba-452c-97f8-326e21ed2bcc

Katzman, S.M., Messerli, M.A., Grossman, A., Harel, T., Barry, D.T., Smith, P.J.S., Chenault, V.M. and Shirihai, O.S. (2004) Mitochondrial metabolism reveals a functional architecture in intact islets of Langerhans from normal and diabetic Psammomys obesus. American Journal of Physiology: Endocrinology and Metabolism, 287 (6), E1090-E1099. (doi:10.1152/?ajpendo.?00044.?2004). (PMID:15339741)

Record type: Article

Abstract

The cells within the intact islet of Langerhans function as a metabolic syncytium, secreting insulin in a coordinated and oscillatory manner in response to external fuel. With increased glucose, the oscillatory amplitude is enhanced, leading to the hypothesis that cells within the islet are secreting with greater synchronization. Consequently, non-insulin-dependent diabetes mellitus (NIDDM; type 2 diabetes)-induced irregularities in insulin secretion oscillations may be attributed to decreased intercellular coordination. The purpose of the present study was to determine whether the degree of metabolic coordination within the intact islet was enhanced by increased glucose and compromised by NIDDM. Experiments were performed with isolated islets from normal and diabetic Psammomys obesus.

Using confocal microscopy and the mitochondrial potentiometric dye rhodamine 123, we measured mitochondrial membrane potential oscillations in individual cells within intact islets. When mitochondrial membrane potential was averaged from all the cells in a single islet, the resultant waveform demonstrated clear sinusoidal oscillations. Cells within islets were heterogeneous in terms of cellular synchronicity (similarity in phase and period), sinusoidal regularity, and frequency of oscillation. Cells within normal islets oscillated with greater synchronicity compared with cells within diabetic islets. The range of oscillatory frequencies was unchanged by glucose or diabetes. Cells within diabetic (but not normal) islets increased oscillatory regularity in response to glucose. These data support the hypothesis that glucose enhances metabolic coupling in normal islets and that the dampening of oscillatory insulin secretion in NIDDM may result from disrupted metabolic coupling.

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Published date: December 2004

Identifiers

Local EPrints ID: 188825
URI: http://eprints.soton.ac.uk/id/eprint/188825
ISSN: 0193-1849
PURE UUID: 22319f5e-ce6a-4423-addc-24e6834edddd
ORCID for P.J.S. Smith: ORCID iD orcid.org/0000-0003-4400-6853

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Date deposited: 03 Jun 2011 12:59
Last modified: 21 Nov 2021 03:04

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Contributors

Author: S.M. Katzman
Author: M.A. Messerli
Author: A. Grossman
Author: T. Harel
Author: D.T. Barry
Author: P.J.S. Smith ORCID iD
Author: V.M. Chenault
Author: O.S. Shirihai

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