Connexin 36 mediates blood cell flow in mouse pancreatic islets

• Published in: American journal of physiology: endocrinology and metabolism 2014-02, Vol.306 (3), p.E324-E331
• Main Authors: Short, Kurt W, Head, W Steve, Piston, David W
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - metabolism; Blood pressure; Cell Tracking; Connexins - physiology; Diabetes; Erythrocytes - physiology; Fluorescence; Gap Junction delta-2 Protein; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - blood supply; Islets of Langerhans - metabolism; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Physiology; Proteins; Regional Blood Flow - genetics
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00523.2013

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.