| First Author | Short KW | Year | 2014 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 306 |
| Issue | 3 | Pages | E324-31 |
| PubMed ID | 24326425 | Mgi Jnum | J:210496 |
| Mgi Id | MGI:5571256 | Doi | 10.1152/ajpendo.00523.2013 |
| Citation | Short KW, et al. (2014) Connexin 36 mediates blood cell flow in mouse pancreatic islets. Am J Physiol Endocrinol Metab 306(3):E324-31 |
| abstractText | The insulin-secreting beta-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 beta-cells in the islet. Connexin 36 (Cx36) gap junctions between islet beta-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 ( approximately 50 mg/dl) or hyperglycemia ( approximately 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 beta-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. |
