title: Connexin 36 mediates blood cell flow in mouse pancreatic islets.
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.
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
authors: Kurt W
authors: KW
authors: Short
authors: W Steve
authors: WS
authors: Head
authors: David W
authors: DW
authors: Piston
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D058948:Cell Tracking; D017630:Connexins / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012039:Regional Blood Flow / Q000235:genetics*; D000097004:Gap Junction delta-2 Protein
chemical_list: D001786:Blood Glucose; D017630:Connexins; D007328:Insulin; D000097004:Gap Junction delta-2 Protein
keywords: gap junction channels; microcirculation; β-cells