Granular detail of β cell structures for insulin secretion

Bogan, Jonathan

doi:10.1083/jcb.202012082

“…В аеробних клітинах потенціал фосфорилювання контролюється за допомогою механізмів, які характерні для мітохондріального метаболізму та викликають компенсаторні зміни в транспорті електронів. Зміни енергетичної функції мітохондрій можуть викликати пошкодження всього електронтранспортного ланцюга мітохондрій [1,14,25]. У хворих цукровим діабетом I та II типів виявлено зниження рівня АТФ та порушення структурно-функціональних властивостей в мембрано-рецепторному апараті клітин [26].…”

Section: обговоренняunclassified

Retinal energy state in rats with experimental diabetes and axial myopia

Михейцева,

Амаієд,

Коломійчук

2023

Oftalmol Zh

0

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Background: Elucidating the pathogenesis of diabetic retinopathy (DR) for further development of methods of treatment and prevention of the disease is an important medical and social task for ophthalmologists. The development of DR in the presence of myopia has some special features. In the presence of myopia, the diabetic complications in the retina are less severe than in emmetropia. The mechanisms of this paradoxical impact of eye myopization on the severity of these complications are, however, still unknown. Purpose: To examine the state of retinal energy metabolism based on evaluation of biochemical markers of mitochondrial function (lactate, pyruvate, adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels and succinate dehydrogenase activity) in rats with streptozotocin (STZ)-induced diabetes that developed in the presence of axial myopia, compared to rats with diabetes alone and those with myopia alone. Material and Methods: High axial myopia was produced in two-week animals by surgically fusing the eyelids of both eyes and maintaining these animals under conditions of reduced illumination for two weeks. A 15 mg/kg intraperitoneal streptozotocin injection for 5 days was used for inducing diabetes mellitus in rats with induced axial myopia and intact rats. Animals in the control group were maintained under conditions of natural illumination. In two months, all rats were euthanized under anesthesia, and their eyes were enucleated. ATP, ADP, lactate, and pyruvate levels were measured in blood and retinal specimens and ATP/ADP ratio and lactate/pyruvate ratio were determined. Succinate dehydrogenase activity was determined in isolated retinal mitochondria. For statistical analysis of biochemical results, Student’s t-test was conducted (Statistica software). Results: Rats with diabetes alone exhibited lower retinal and plasma energy metabolism characteristics (ATP, ADP, and succinate dehydrogenase activity), and developed retinal hypoxia, with retinal lactate and pyruvate levels being 1.838-fold and 1.455-fold higher, respectively, and their ratio, 26.5% higher, compared to controls. In animals with STZ-induced diabetes in the presence of axial hypoxia, retinal lactate and pyruvate levels were 20.2% and 15.5% lower, respectively, and their ratio was lower (36.5 versus 38.7), compared to rats with diabetes alone, indicating lower hypoxia in the setting of eye myopization. In addition, in rats with diabetes in the presence of axial hypoxia, plasma and retinal ATP levels were 21.8% and 21.2% higher, respectively, and retinal succinate dehydrogenase activity, 20.8% higher, compared to rats with diabetes alone. Conclusion: In experimental diabetes, an increase in the axial length of the eye (i.e., eye myopization) is accompanied by activation of energy processes and the development of hypoxia adaptation in retinal cells.

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“…Such multi-faceted involvement of MT transport in secretion regulation is made possible by a complex architecture of MT networks in beta cells. To this end, interior beta-cell MTs are twisted and interlocked (Varadi, Tsuboi, Johnson-Cadwell, Allan, & Rutter, 2003;Zhu et al, 2015), which makes them dramatically distinct from radially organized MT arrays well-studied in generic cultured cell models and explains the predominantly non-directional nature of IG transport (Bogan, 2021;Bracey, Gu, & Kaverina, 2022). Importantly, withdrawal of IGs and secretion restriction is achieved by a prominent array of MTs underlying cell membrane (Bracey et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in pancreatic beta cells

Bracey

¹

,

Noguchi

²

,

Edwards

³

et al. 2023

Preprint

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In pancreatic islet beta cells, molecular motors use cytoskeletal polymers microtubules as tracks for intracellular transport of insulin secretory granules. Beta-cell microtubule network has a complex architecture and is non-directional, which provide insulin granules at the cell periphery for rapid secretion response, yet to avoid over-secretion and subsequent hypoglycemia. We have previously characterized a peripheral sub-membrane microtubule array, which is critical for withdrawal of excessive insulin granules from the secretion sites. Microtubules in beta cells originate at the Golgi in the cell interior, and how the peripheral array is formed is unknown. Using real-time imaging and photo-kinetics approaches in clonal mouse pancreatic beta cells MIN6, we now demonstrate that kinesin KIF5B, a motor protein with a capacity to transport microtubules as cargos, slides existing microtubules to the cell periphery and aligns them to each other along the plasma membrane. Moreover, like many physiological beta-cell features, microtubule sliding is facilitated by a high glucose stimulus. These new data, together with our previous report that in high glucose sub-membrane MT array is destabilized to allow for robust secretion, indicate that MT sliding is another integral part of glucose-triggered microtubule remodeling, likely replacing destabilized peripheral microtubules to prevent their loss over time and beta-cell malfunction.

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Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in pancreatic beta cells

Bracey,

Noguchi,

Edwards

et al. 2023

Preprint

0

View full text Add to dashboard Cite

In pancreatic islet beta cells, molecular motors use cytoskeletal polymers microtubules as tracks for intracellular transport of insulin secretory granules. Beta-cell microtubule network has a complex architecture and is non-directional, which provide insulin granules at the cell periphery for rapid secretion response, yet to avoid over-secretion and subsequent hypoglycemia. We have previously characterized a peripheral sub-membrane microtubule array, which is critical for withdrawal of excessive insulin granules from the secretion sites. Microtubules in beta cells originate at the Golgi in the cell interior, and how the peripheral array is formed is unknown. Using real-time imaging and photo-kinetics approaches in clonal mouse pancreatic beta cells MIN6, we now demonstrate that kinesin KIF5B, a motor protein with a capacity to transport microtubules as cargos, slides existing microtubules to the cell periphery and aligns them to each other along the plasma membrane. Moreover, like many physiological beta-cell features, microtubule sliding is facilitated by a high glucose stimulus. These new data, together with our previous report that in high glucose sub-membrane MT array is destabilized to allow for robust secretion, indicate that MT sliding is another integral part of glucose-triggered microtubule remodeling, likely replacing destabilized peripheral microtubules to prevent their loss over time and beta-cell malfunction.

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Granular detail of β cell structures for insulin secretion

Cited by 4 publications

References 11 publications

Retinal energy state in rats with experimental diabetes and axial myopia

Retinal energy state in rats with experimental diabetes and axial myopia

Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in pancreatic beta cells

Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in pancreatic beta cells

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