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Diabetologia
Published in: Diabetologia 4/2013

01-04-2013 | Article

Loss of coupling between calcium influx, energy consumption and insulin secretion associated with development of hyperglycaemia in the UCD-T2DM rat model of type 2 diabetes

Authors: A. M. Rountree, B. J. Reed, B. P. Cummings, S.-R. Jung, K. L. Stanhope, J. L. Graham, S. C. Griffen, R. L. Hull, P. J. Havel, I. R. Sweet

Published in: Diabetologia | Issue 4/2013

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Abstract

Aims/hypothesis

Previous studies on isolated islets have demonstrated tight coupling between calcium (Ca2+) influx and oxygen consumption rate (OCR) that is correlated with insulin secretion rate (ISR). To explain these observations, we have proposed a mechanism whereby the activation of a highly energetic process (Ca2+/metabolic coupling process [CMCP]) by Ca2+ mediates the stimulation of ISR. The aim of the study was to test whether impairment of the CMCP could play a role in the development of type 2 diabetes.

Methods

Glucose- and Ca2+-mediated changes in OCR and ISR in isolated islets were compared with the time course of changes of plasma insulin concentrations observed during the progression to hyperglycaemia in a rat model of type-2 diabetes (the University of California at Davis type 2 diabetes mellitus [UCD-T2DM] rat). Islets were isolated from UCD-T2DM rats before, 1 week, and 3 weeks after the onset of hyperglycaemia.

Results

Glucose stimulation of cytosolic Ca2+ and OCR was similar for islets harvested before and 1 week after the onset of hyperglycaemia. In contrast, a loss of decrement in islet OCR and ISR in response to Ca2+ channel blockade coincided with decreased fasting plasma insulin concentrations observed in rats 3 weeks after the onset of hyperglycaemia.

Conclusions/interpretation

These results suggest that phenotypic impairment of diabetic islets in the UCD-T2DM rat is downstream of Ca2+ influx and involves unregulated stimulation of the CMCP. The continuously elevated levels of CMCP induced by chronic hyperglycaemia in these islets may mediate the loss of islet function.
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Metadata
Title
Loss of coupling between calcium influx, energy consumption and insulin secretion associated with development of hyperglycaemia in the UCD-T2DM rat model of type 2 diabetes
Authors
A. M. Rountree
B. J. Reed
B. P. Cummings
S.-R. Jung
K. L. Stanhope
J. L. Graham
S. C. Griffen
R. L. Hull
P. J. Havel
I. R. Sweet
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 4/2013
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2808-6

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