Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice

Gregersen, Søren; Thomsen, Jan Lykke Scheel; Brock, Birgitte; Hermansen, Kjeld

doi:10.1007/bf00400650

Cited by 45 publications

(22 citation statements)

References 23 publications

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“…Tsp-1 is a natural inhibitor of angiogenesis expressed in islet endothelium, which we have recently observed is important for beta cell differentiation in TSP-1-deficient mice [22]. ET-1 is a potent vasoconstrictor derived from endothelial cells, which is known to stimulate insulin release [23]. HGF was recently shown by us to be expressed by islet endothelial cells and to stimulate beta cell proliferation [13].…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell signalling supports pancreatic beta cell function in the rat

et al. 2009

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Aims/hypothesis The proximity of endothelial cells and beta cells in islets by necessity means that they are exposed to each other's products. Whereas islet endothelial cells require signals from beta cells to function properly, endothelin-1, thrombospondin-1 and laminins, among others, have been identified as endothelial-derived molecules, although their full effects on beta cells have not been explored. We tested the hypothesis that islet endothelialderived products affect beta cell function. Methods Endothelial cells from rat islets were proliferated and purified. Endothelium-conditioned culture medium (ECCM) was obtained by maintaining the endothelial cells in culture medium. Islet function was evaluated following exposure of cultured islets to standard culture medium or ECCM. Changes in mRNA levels for key beta cell metabolic enzymes were also measured in islets after ECCM exposure.Results Glucose-stimulated insulin release and islet insulin content were markedly enhanced by exposure to ECCM. This was at least partly explained by improved mitochondrial function, as assessed by glucose oxidation and an upregulation of the mitochondrial gene for glycerol-3-phosphate dehydrogenase (mGpdh [also known as Gpd2]), combined with upregulation of the rate-limiting enzyme in the glycolysis, glucokinase, in the islets. The intracellular degradation of insulin was also decreased in the islets. Islet endothelial cells produced laminins, and the positive effects of islet endothelial cells were prevented by addition of a neutralising antibody to the β1-chain of laminin. Addition of exogenous laminin stimulated islet function. Conclusions/interpretation This study provides proof of principle that endothelial cells can affect the function of beta cells in their vicinity and that this is at least partially mediated by laminins.

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Section: Discussionmentioning

confidence: 99%

Endothelial cell signalling supports pancreatic beta cell function in the rat

et al. 2009

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“…In addition to its antiangiogenic properties, thrombospondin-1 activates latent transforming growth factor-b (a potent regulator of adult b-cell insulin gene transcription and islet function [18]). Endothelin-1, a vasoconstrictive protein, is produced by ECs and may directly stimulate insulin secretion in b-cells (19). Hepatocyte growth factor (HGF) is a proangiogenic factor expressed by intraislet ECs (20).…”

Section: Soluble Factorsmentioning

confidence: 99%

The β-Cell/EC Axis: How Do Islet Cells Talk to Each Other?

et al. 2013

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Within the pancreatic islet, the β-cell represents the ultimate biosensor. Its central function is to accurately sense glucose levels in the blood and consequently release appropriate amounts of insulin. As the only cell type capable of insulin production, the β-cell must balance this crucial workload with self-preservation and, when required, regeneration. Evidence suggests that the β-cell has an important ally in intraislet endothelial cells (ECs). As well as providing a conduit for delivery of the primary input stimulus (glucose) and dissemination of its most important effector (insulin), intraislet blood vessels deliver oxygen to these dense clusters of metabolically active cells. Furthermore, it appears that ECs directly impact insulin gene expression and secretion and β-cell survival. This review discusses the molecules and pathways involved in the crosstalk between β-cells and intraislet ECs. The evidence supporting the intraislet EC as an important partner for β-cell function is examined to highlight the relevance of this axis in the context of type 1 and type 2 diabetes. Recent work that has established the potential of ECs or their progenitors to enhance the re-establishment of glycemic control following pancreatic islet transplantation in animal models is discussed.

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“…Islet cPLA2 activation is increased in insulin-resistant mice [7]. Furthermore, TIP60 interacts with the ETA receptors in various tissues and we have previously demonstrated that ET-1 influences insulin secretion [8,9].…”

Section: Introductionmentioning

confidence: 93%

Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells

Nordentoft

Jeppesen²,

Nielsen³

et al. 2007

Rev Diabet Stud

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■ AbstractIn the present study we investigate the expression levels of cytosolic phospholipase A 2 α (cPLA 2 α) interacting histone acetyl transferase proteins TIP60α and TIP60β in nondiabetic C57BL wild-type mice and obese type 2 diabetic KKAy model mice. The aim was to test our hypothesis that TIP60 plays a regulatory role in glucose-stimulated insulin secretion from pancreatic β-cells. MATERIAL AND METHODS: Ten obese diabetic KKAy mice and ten nondiabetic C57BL mice were fed a standard chow diet. After nine weeks, islet RNA was purified and used to measure TIP60 expression. We investigated the effect of TIP60α and TIP60β on glucose-stimulated insulin secretion by transient and stable overexpression in the pancreatic mouse β-cell line MIN6 and the rat β-cell line INS-1E. RESULTS: We found that non-diabetic C57BL mice and diabetic KKAy mice have the same level of both the α and β splice forms of TIP60. Furthermore, we demonstrated that transient and stable expression of TIP60 in INS-1E cells affects neither glucose-stimulated insulin secretion, insulin output nor cell insulin content. Also susceptibility to developing glucotoxicity was unaffected. CONCLUSION: TIP60 overexpression does not affect glucose stimulated insulin secretion, insulin content or abnormal β-cell function during glucotoxicity.

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Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice

Cited by 45 publications

References 23 publications

Endothelial cell signalling supports pancreatic beta cell function in the rat

Endothelial cell signalling supports pancreatic beta cell function in the rat

The β-Cell/EC Axis: How Do Islet Cells Talk to Each Other?

Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells

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