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The structure of in...
The structure of insulin granule core determines secretory capacity being reduced in type-2 diabetes
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- Barghouth, Mohammad (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Jiang, Xiaoping (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Southwest University
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- Nagao, Mototsugu (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Chen, Ning (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Fudan University
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- Yang, Daowei (author)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,Other operations, LTH,Faculty of Engineering, LTH,Diabetes - Islet Patophysiology,Lund University Research Groups,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH
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Ye, Yingying (author)
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- Luan, Cheng (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Gomez, Maria F. (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Blom, Anna M. (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Department of Translational Medicine,Faculty of Medicine,Protein Chemistry, Malmö,Lund University Research Groups
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- Wollheim, Claes B (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Geneva University Hospital
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Medicinska fakulteten,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Faculty of Medicine,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Renström, Erik (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,Lunds Tekniska Högskola,Diabetes - Islet Patophysiology,Lund University Research Groups,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH
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- Zhang, Enming (author)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,Other operations, LTH,Faculty of Engineering, LTH,Diabetes - Islet Patophysiology,Lund University Research Groups,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH
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(creator_code:org_t)
- Cold Spring Harbor Laboratory, 2022
- English.
- Related links:
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http://dx.doi.org/10... (free)
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https://www.biorxiv....
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Exocytosis in excitable cells is essential for their physiological functions. Although the exocytotic machinery controlling cellular secretion has been well investigated, the function of the vesicular cargo, i.e. secretory granular content remains obscure. Here we combine dSTORM imaging and single-domain insulin antibody, to dissect the in situ structure of insulin granule cores (IGCs) at nano level. We demonstrate that the size and shape of the IGCs can be regulated by the juxta-granular molecules Nucleobindin-2 and Enolase-1, that further contribute to the stimulated insulin secretion. IGCs located at the plasma membrane are larger than those in the cytosol. The IGCs size is decreased by ∼20% after glucose stimulation due to the release of the peripheral part of IGCs through incomplete granule fusion. Importantly, the reduction of the IGCs size is also observed in non-stimulatory pancreatic β-cells from diabetic db/db mice, Akita (Ins2+/-) mice and human Type-2 diabetic donors, in accordance with impaired secretion. These findings overall highlight the structure of exocytotic insulin cores as a novel modality amenable to targeting in the stimulated exocytosis in β-cells with impaired insulin secretion.Competing Interest StatementThe authors have declared no competing interest.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- ovr (subject category)
- vet (subject category)
To the university's database
- By the author/editor
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Barghouth, Moham ...
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Jiang, Xiaoping
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Nagao, Mototsugu
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Chen, Ning
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Yang, Daowei
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Ye, Yingying
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show more...
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Luan, Cheng
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Gomez, Maria F.
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Blom, Anna M.
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Wollheim, Claes ...
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Eliasson, Lena
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Renström, Erik
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Zhang, Enming
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- By the university
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Lund University