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
Identifieur interne : 000193 ( Main/Exploration ); précédent : 000192; suivant : 000194Loss 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
Auteurs : A. M. Rountree [États-Unis] ; B. J. Reed [États-Unis] ; B. P. Cummings [États-Unis] ; S.-R. Jung [États-Unis] ; K. L. Stanhope [États-Unis] ; J. L. Graham [États-Unis] ; S. C. Griffen [États-Unis] ; R. L. Hull [États-Unis] ; P. J. Havel [États-Unis] ; I. R. Sweet [États-Unis]Source :
- Diabetologia : (Berlin) [ 0012-186X ] ; 2013.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Calcium.
English descriptors
- KwdEn :
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.
Affiliations:
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term>
<term>Animal model</term>
<term>Calcium</term>
<term>Development</term>
<term>Hyperglycemia</term>
<term>Insulin</term>
<term>Oxygen consumption</term>
<term>Rat</term>
<term>Secretion</term>
<term>Type 2 diabetes</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Calcium</term>
<term>Insuline</term>
<term>Sécrétion</term>
<term>Développement</term>
<term>Animal</term>
<term>Hyperglycémie</term>
<term>Modèle animal</term>
<term>Diabète de type 2</term>
<term>Consommation oxygène</term>
<term>Rat</term>
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<front><div type="abstract" xml:lang="en">Aims/hypothesis Previous studies on isolated islets have demonstrated tight coupling between calcium (Ca<sup>2+</sup>
) 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 (Ca<sup>2+</sup>
/metabolic coupling process [CMCP]) by Ca<sup>2+</sup>
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 Ca<sup>2+</sup>
-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 Ca<sup>2+</sup>
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 Ca<sup>2+</sup>
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 Ca<sup>2+</sup>
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.</div>
</front>
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<name sortKey="Reed, B J" sort="Reed, B J" uniqKey="Reed B" first="B. J." last="Reed">B. J. Reed</name>
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<name sortKey="Sweet, I R" sort="Sweet, I R" uniqKey="Sweet I" first="I. R." last="Sweet">I. R. Sweet</name>
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