Cholesterol metabolism and pancreatic β-cell function

Fryirs, Michelle; Barter, Philip J.; Rye, Kerry‐Anne

doi:10.1097/mol.0b013e32832ac180

Cited by 85 publications

(63 citation statements)

References 26 publications

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“…GSIS from pancreatic ␤-cells represents an example of regulated secretion, which shares some common regulatory mechanisms with other secretory systems. Recent studies indicate that excess cholesterol impairs ␤-cell function and GSIS (10,11,57,58). The data presented here suggest that membrane cholesterol abundance regulates glucose-stimulated actin reorganization, membrane depolarization, and insulin secretion by controlling PIP 2 metabolism in ␤-cells.…”

Section: Discussionmentioning

confidence: 68%

Cholesterol Regulates Glucose-stimulated Insulin Secretion through Phosphatidylinositol 4,5-Bisphosphate

Hao

Bogan

2009

Journal of Biological Chemistry

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Membrane cholesterol modulates the ability of glucose to stimulate insulin secretion from pancreatic ␤-cells. The molecular mechanism by which this occurs is not understood. Here, we show that in cultured ␤-cells, cholesterol acts through phosphatidylinositol 4,5-bisphosphate (PIP 2 ) to regulate actin dynamics, plasma membrane potential, and glucose-stimulated insulin secretion. Cholesterol-overloaded ␤-cells exhibited decreased PIP 2 hydrolysis, with diminished glucose-induced actin reorganization, membrane depolarization, and insulin secretion. The converse findings were observed in cholesteroldepleted cells. These results support a model in which cholesterol depletion is coupled through PIP 2 to enhance both plasma membrane Ca 2؉ influx from the extracellular space, as well as inositol 1,4,5-triphosphate-stimulated Ca 2؉ efflux from intracellular stores. The inability to increase cytosolic Ca 2؉ may be the main underlying factor to account for impaired glucosestimulated insulin secretion in cholesterol-overloaded ␤-cells.

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Section: Discussionmentioning

confidence: 68%

Cholesterol Regulates Glucose-stimulated Insulin Secretion through Phosphatidylinositol 4,5-Bisphosphate

Hao

Bogan

2009

Journal of Biological Chemistry

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“…We cannot examine why increased BMI was a stronger predictor of pancreas failure in T2DM patients compared with T1DM patients. However, we can hypothesize that in T2DM recipients increased BMI may be a marker of plurimetabolic syndrome, with insulin resistance, hyperinsulinemia, dyslipidemia, vascular disease, and increased prothrombotic activity that may contribute to pancreas loss (22)(23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Simultaneous Pancreas-Kidney Transplantation in Type 2 Diabetic Recipients

Sampaio

Kuo

Bunnapradist

2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Type 2 diabetic patients with end-stage renal disease may receive a simultaneous pancreas-kidney (SPK) transplant. However, outcomes are not well described. Risks for death and graft failure were examined in SPK type 2 diabetic recipients.Design, setting, participants, & measurements Using the United Network for Organ Sharing database, outcomes of SPK transplants were compared between type 2 and type 1 diabetic recipients. All primary SPK adult recipients transplanted between 2000 and 2007 (n ϭ 6756) were stratified according to end-stage pancreas disease diagnosis (type 1: nϭ6141, type 2: nϭ582). Posttransplant complications and risks for death and kidney/pancreas graft failure were compared. ResultsOf the 6756 SPK transplants, 8.6% were performed in recipients with a type 2 diabetes diagnosis. Rates of delayed kidney graft function and primary kidney nonfunction were higher in the type 2 diabetics. Five-year overall and death-censored kidney graft survival were inferior in type 2 diabetics. After adjustment for other risk factors, including recipient (age, race, body weight, dialysis time, and cardiovascular comorbidities), donor, and transplant immune characteristics, type 2 diabetes was not associated with increased risk for death or kidney or pancreas failure when compared with type 1 diabetic recipients. ConclusionsAfter adjustment for other risk factors, SPK recipients with type 2 diabetes diagnosis were not at increased risk for death, kidney failure, or pancreas failure when compared with recipients with type 1 diabetes.

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“…The LXR target genes ABCA1 and ABCG1 play critical roles in maintaining beta cell function by regulating cellular cholesterol homeostasis. Indeed, cellular cholesterol accumulation is an emerging mechanism leading to beta cell dysfunction in T2D (44). Deficiency of either ABCA1 or ABCG1 in beta cells leads to alterations in cellular cholesterol distribution and impaired insulin secretion (45).…”

Section: Discussionmentioning

confidence: 99%

Group X Secretory Phospholipase A2 Regulates Insulin Secretion through a Cyclooxygenase-2-dependent Mechanism

Shridas

Zahoor

Forrest

et al. 2014

Journal of Biological Chemistry

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Background: Arachidonic acid and its metabolites regulate pancreatic glucose-stimulated insulin secretion (GSIS) through multiple mechanisms. Results: Group X secretory phospholipase A 2 (GX sPLA 2 ) suppresses GSIS; suppression was abolished when COX-2 activity or PGE2-EP3 receptor signaling were inhibited. Conclusion: GX sPLA 2 inhibits GSIS by augmenting PGE2 production. Significance: GX sPLA 2 may be targeted for ameliorating beta cell dysfunction in type 2 diabetes.

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Cholesterol metabolism and pancreatic β-cell function

Cited by 85 publications

References 26 publications

Cholesterol Regulates Glucose-stimulated Insulin Secretion through Phosphatidylinositol 4,5-Bisphosphate

Cholesterol Regulates Glucose-stimulated Insulin Secretion through Phosphatidylinositol 4,5-Bisphosphate

Outcomes of Simultaneous Pancreas-Kidney Transplantation in Type 2 Diabetic Recipients

Group X Secretory Phospholipase A2 Regulates Insulin Secretion through a Cyclooxygenase-2-dependent Mechanism

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