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Am J Physiol Endocrinol Metab. 2014 Feb;306(3):E324-31. doi: 10.1152/ajpendo.00523.2013. Epub 2013 Dec 10.

Connexin 36 mediates blood cell flow in mouse pancreatic islets.

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.

Abstract

The insulin-secreting β-cells are contained within islets of Langerhans, which are highly vascularized. Blood cell flow rates through islets are glucose-dependent, even though there are no changes in blood cell flow within in the surrounding exocrine pancreas. This suggests a specific mechanism of glucose-regulated blood flow in the islet. Pancreatic islets respond to elevated glucose with synchronous pulses of electrical activity and insulin secretion across all β-cells in the islet. Connexin 36 (Cx36) gap junctions between islet β-cells mediate this synchronization, which is lost in Cx36 knockout mice (Cx36(-/-)). This leads to glucose intolerance in these mice, despite normal plasma insulin levels and insulin sensitivity. Thus, we sought to investigate whether the glucose-dependent changes in intraislet blood cell flow are also dependent on coordinated pulsatile electrical activity. We visualized and quantified blood cell flow using high-speed in vivo fluorescence imaging of labeled red blood cells and plasma. With the use of a live animal glucose clamp, blood cell flow was measured during either hypoglycemia (∼50 mg/dl) or hyperglycemia (∼300 mg/dl). In contrast to the large glucose-dependent islet blood velocity changes observed in wild-type mice, only minimal differences are observed in both Cx36(+/-) and Cx36(-/-) mice. This observation supports a novel model where intraislet blood cell flow is regulated by the coordinated electrical activity in the islet β-cells. Because Cx36 expression and function is reduced in type 2 diabetes, the resulting defect in intraislet blood cell flow regulation may also play a significant role in diabetic pathology.

KEYWORDS:

gap junction channels; microcirculation; β-cells

PMID:
24326425
PMCID:
PMC3920012
DOI:
10.1152/ajpendo.00523.2013
[Indexed for MEDLINE]
Free PMC Article

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