Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice. / Gustavsson, Natalia; Lao, Ye; Maximov, Anton; Chuang, Jen-Chieh; Kostromina, Elena; Repa, Joyce J; Li, Cai; Radda, George K; Südhof, Thomas C; Han, Weiping.

In: National Academy of Sciences. Proceedings, Vol. 105, No. 10, 11.03.2008, p. 3992-7.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Gustavsson, N, Lao, Y, Maximov, A, Chuang, J-C, Kostromina, E, Repa, JJ, Li, C, Radda, GK, Südhof, TC & Han, W 2008, 'Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice', National Academy of Sciences. Proceedings, vol. 105, no. 10, pp. 3992-7. https://doi.org/10.1073/pnas.0711700105

APA

Gustavsson, N., Lao, Y., Maximov, A., Chuang, J-C., Kostromina, E., Repa, J. J., Li, C., Radda, G. K., Südhof, T. C., & Han, W. (2008). Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice. National Academy of Sciences. Proceedings, 105(10), 3992-7. https://doi.org/10.1073/pnas.0711700105

Vancouver

Gustavsson N, Lao Y, Maximov A, Chuang J-C, Kostromina E, Repa JJ et al. Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice. National Academy of Sciences. Proceedings. 2008 Mar 11;105(10):3992-7. https://doi.org/10.1073/pnas.0711700105

Author

Gustavsson, Natalia ; Lao, Ye ; Maximov, Anton ; Chuang, Jen-Chieh ; Kostromina, Elena ; Repa, Joyce J ; Li, Cai ; Radda, George K ; Südhof, Thomas C ; Han, Weiping. / Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice. In: National Academy of Sciences. Proceedings. 2008 ; Vol. 105, No. 10. pp. 3992-7.

Bibtex

@article{ff0b8b6f71c341208298fea2254a4a28,
title = "Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice",
abstract = "Vertebrates express at least 15 different synaptotagmins with the same domain structure but diverse localizations and tissue distributions. Synaptotagmin-1,-2, and -9 act as calcium sensors for the fast phrase of neurotransmitter release, and synaptotagmin-12 acts as a calcium-independent modulator of release. The exact functions of the remaining 11 synaptotagmins, however, have not been established. By analogy to the role of synaptotagmin-1, -2, and -9 in neurotransmission, these other synaptotagmins may serve as Ca(2+) transducers regulating other Ca(2+)-dependent membrane processes, such as insulin secretion in pancreatic beta-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic beta-cells. To determine whether synaptotagmin-7 regulates Ca(2+)-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor controlling insulin secretion in pancreatic beta cells.",
keywords = "Adipose Tissue, Animals, Body Weight, Calcium Signaling, Female, Glucose, Glucose Intolerance, Insulin, Insulin-Secreting Cells, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, NADP, Synaptotagmins, Journal Article, Research Support, Non-U.S. Gov't",
author = "Natalia Gustavsson and Ye Lao and Anton Maximov and Jen-Chieh Chuang and Elena Kostromina and Repa, {Joyce J} and Cai Li and Radda, {George K} and S{\"u}dhof, {Thomas C} and Weiping Han",
year = "2008",
month = mar,
day = "11",
doi = "10.1073/pnas.0711700105",
language = "English",
volume = "105",
pages = "3992--7",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "10",

}

RIS

TY - JOUR

T1 - Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice

AU - Gustavsson, Natalia

AU - Lao, Ye

AU - Maximov, Anton

AU - Chuang, Jen-Chieh

AU - Kostromina, Elena

AU - Repa, Joyce J

AU - Li, Cai

AU - Radda, George K

AU - Südhof, Thomas C

AU - Han, Weiping

PY - 2008/3/11

Y1 - 2008/3/11

N2 - Vertebrates express at least 15 different synaptotagmins with the same domain structure but diverse localizations and tissue distributions. Synaptotagmin-1,-2, and -9 act as calcium sensors for the fast phrase of neurotransmitter release, and synaptotagmin-12 acts as a calcium-independent modulator of release. The exact functions of the remaining 11 synaptotagmins, however, have not been established. By analogy to the role of synaptotagmin-1, -2, and -9 in neurotransmission, these other synaptotagmins may serve as Ca(2+) transducers regulating other Ca(2+)-dependent membrane processes, such as insulin secretion in pancreatic beta-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic beta-cells. To determine whether synaptotagmin-7 regulates Ca(2+)-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor controlling insulin secretion in pancreatic beta cells.

AB - Vertebrates express at least 15 different synaptotagmins with the same domain structure but diverse localizations and tissue distributions. Synaptotagmin-1,-2, and -9 act as calcium sensors for the fast phrase of neurotransmitter release, and synaptotagmin-12 acts as a calcium-independent modulator of release. The exact functions of the remaining 11 synaptotagmins, however, have not been established. By analogy to the role of synaptotagmin-1, -2, and -9 in neurotransmission, these other synaptotagmins may serve as Ca(2+) transducers regulating other Ca(2+)-dependent membrane processes, such as insulin secretion in pancreatic beta-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic beta-cells. To determine whether synaptotagmin-7 regulates Ca(2+)-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor controlling insulin secretion in pancreatic beta cells.

KW - Adipose Tissue

KW - Animals

KW - Body Weight

KW - Calcium Signaling

KW - Female

KW - Glucose

KW - Glucose Intolerance

KW - Insulin

KW - Insulin-Secreting Cells

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Mutant Strains

KW - NADP

KW - Synaptotagmins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1073/pnas.0711700105

DO - 10.1073/pnas.0711700105

M3 - Journal article

C2 - 18308938

VL - 105

SP - 3992

EP - 3997

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 10

ER -

ID: 172513294