Abstract:Serum insulin concentration per se does not affect islet blood flow, whereas the ambient blood glucose concentration is of major importance in this context.
“…For the wild-type mouse shown, the blood glucose is cycled two times from hyperglycemia to hypoglycemia. The average islet blood cell velocity follows these changes, being faster with hyperglycemic conditions and slower with hypoglycemic conditions, in agreement with previous reports (25,42). For the Cx36 ϩ/Ϫ and Cx36 Ϫ/Ϫ mice shown, blood glucose is cycled from hyperglycemia to hypoglycemia, and back to hyperglycemia.…”
Section: E326 Connexin 36 Mediates Blood Cell Flow In Isletssupporting
confidence: 79%
“…ities is that they are glucose-dependent: under hyperglycemic conditions (ϳ300 mg/dl glucose concentration) islet blood cells move faster, and under hypoglycemic conditions (ϳ50 mg/dl glucose concentration) they move more slowly (25,42). In contrast, blood cell velocities in the exocrine pancreas appear to be independent of glucose levels.…”
mentioning
confidence: 87%
“…In contrast, the velocity differences are robust and reproducible, and thus allow behavioral variations between genotypes and glycemic levels to be measured. Measurement of velocity differences in a single animal under various conditions is not possible in bead flow experiments (24,25) and is thus a major advantage of our live animal blood flow imaging approach.…”
Section: E326 Connexin 36 Mediates Blood Cell Flow In Isletsmentioning
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.
“…For the wild-type mouse shown, the blood glucose is cycled two times from hyperglycemia to hypoglycemia. The average islet blood cell velocity follows these changes, being faster with hyperglycemic conditions and slower with hypoglycemic conditions, in agreement with previous reports (25,42). For the Cx36 ϩ/Ϫ and Cx36 Ϫ/Ϫ mice shown, blood glucose is cycled from hyperglycemia to hypoglycemia, and back to hyperglycemia.…”
Section: E326 Connexin 36 Mediates Blood Cell Flow In Isletssupporting
confidence: 79%
“…ities is that they are glucose-dependent: under hyperglycemic conditions (ϳ300 mg/dl glucose concentration) islet blood cells move faster, and under hypoglycemic conditions (ϳ50 mg/dl glucose concentration) they move more slowly (25,42). In contrast, blood cell velocities in the exocrine pancreas appear to be independent of glucose levels.…”
mentioning
confidence: 87%
“…In contrast, the velocity differences are robust and reproducible, and thus allow behavioral variations between genotypes and glycemic levels to be measured. Measurement of velocity differences in a single animal under various conditions is not possible in bead flow experiments (24,25) and is thus a major advantage of our live animal blood flow imaging approach.…”
Section: E326 Connexin 36 Mediates Blood Cell Flow In Isletsmentioning
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.
“…It could, however, be speculated that increased endocrine cell release from the islets could directly affect the islet afferent islet arterioles to increase blood perfusion. We have previously noted that insulin in itself does not affect islet blood flow (26), whereas high doses of islet amyloid polypeptide (IAPP) (27), somatostatin (28) and pancreatic polypeptide (29) may do so. However, the present findings suggest that neither insulin, IAPP or any other product co-secreted with insulin, e.g.…”
Background: Repeated administration of glucose in vivo leads to a time-dependent potentiation of insulin release. Glucose is also known to stimulate pancreatic islet blood flow, but whether this is associated with a time-dependent potentiation is unknown. We therefore repeatedly administered glucose to anesthetized rats and evaluated effects on insulin release and islet blood flow. Methods: Male Wistar-Furth rats, anesthetized with thiobutabarbital, were injected intravenously with 1 ml of saline or glucose at times 0, 30 and 60 min. The combinations used were saline + saline + saline (SSS), glucose + saline + saline (GSS), saline + saline + glucose (SSG) and glucose + glucose + glucose (GGG). Regional organ blood flow values were measured 3 min after the final injection with a microsphere technique, and at this time also serum insulin concentrations were determined with ELISA.Results: Serum insulin concentrations as well as total pancreatic, pancreatic islet and duodenal blood flow were higher in SSG and GGG-treated rats when compared to those given SSS and GSS. However, only insulin concentrations, not blood flow values, were higher in GGG rats when compared to SSG animals. Conclusions: Glucose-induced time-dependent potentiation of insulin release occurs in vivo in thiobutabarbital-anesthetized rats, but is not associated with a further increase in islet blood flow.
“…The highly specialized intra-islet vasculature is lined by fenestrated endothelial cells. Blood flow changes during hyperglycemia and hypoglycemia conditions (3,4). Alpha islet cells are "downstream" from beta cells in terms of blood flow (5-11) and beta cell secretory products like zinc, gamma aminobutyric acid (GABA), and insulin likely impact alpha cell function (12)(13)(14)(15).…”
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