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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/E1090    most recent 00044.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Katzman, S. M. Articles by Shirihai, O. S. Search for Related Content PubMed PubMed Citation Articles by Katzman, S. M. Articles by Shirihai, O. S.

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

¹Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston 02111; ²BioCurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts 02543; ³National Aeronautics and Space Administration, Washington, District of Columbia 20546; ⁴Impulse Dynamics, Tirat Hacarmel, 39120 Israel; and ⁵Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118

Submitted 29 January 2004 ; accepted in final form 6 August 2004

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.

diabetes; metabolic oscillations; mitochondrial membrane potential; rhodamine 123