PUBLICATION
SerpinB1 Promotes Pancreatic β Cell Proliferation
- Authors
- El Ouaamari, A., Dirice, E., Gedeon, N., Hu, J., Zhou, J.Y., Shirakawa, J., Hou, L., Goodman, J., Karampelias, C., Qiang, G., Boucher, J., Martinez, R., Gritsenko, M.A., De Jesus, D.F., Kahraman, S., Bhatt, S., Smith, R.D., Beer, H.D., Jungtrakoon, P., Gong, Y., Goldfine, A.B., Liew, C.W., Doria, A., Andersson, O., Qian, W.J., Remold-O'Donnell, E., Kulkarni, R.N.
- ID
- ZDB-PUB-151225-2
- Date
- 2016
- Source
- Cell Metabolism 23(1): 194-205 (Journal)
- Registered Authors
- Karampelias, Christos
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Proliferation*
- Cells, Cultured
- Humans
- Insulin Resistance
- Insulin-Secreting Cells/physiology*
- Liver/metabolism
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Receptor, Insulin/genetics
- Receptor, Insulin/metabolism
- Serpins/physiology*
- Signal Transduction
- Zebrafish
- PubMed
- 26701651 Full text @ Cell Metab.
Citation
El Ouaamari, A., Dirice, E., Gedeon, N., Hu, J., Zhou, J.Y., Shirakawa, J., Hou, L., Goodman, J., Karampelias, C., Qiang, G., Boucher, J., Martinez, R., Gritsenko, M.A., De Jesus, D.F., Kahraman, S., Bhatt, S., Smith, R.D., Beer, H.D., Jungtrakoon, P., Gong, Y., Goldfine, A.B., Liew, C.W., Doria, A., Andersson, O., Qian, W.J., Remold-O'Donnell, E., Kulkarni, R.N. (2016) SerpinB1 Promotes Pancreatic β Cell Proliferation. Cell Metabolism. 23(1):194-205.
Abstract
Although compensatory islet hyperplasia in response to insulin resistance is a recognized feature in diabetes, the factor(s) that promote β cell proliferation have been elusive. We previously reported that the liver is a source for such factors in the liver insulin receptor knockout (LIRKO) mouse, an insulin resistance model that manifests islet hyperplasia. Using proteomics we show that serpinB1, a protease inhibitor, which is abundant in the hepatocyte secretome and sera derived from LIRKO mice, is the liver-derived secretory protein that regulates β cell proliferation in humans, mice, and zebrafish. Small-molecule compounds, that partially mimic serpinB1 effects of inhibiting elastase activity, enhanced proliferation of β cells, and mice lacking serpinB1 exhibit attenuated β cell compensation in response to insulin resistance. Finally, SerpinB1 treatment of islets modulated proteins in growth/survival pathways. Together, these data implicate serpinB1 as an endogenous protein that can potentially be harnessed to enhance functional β cell mass in patients with diabetes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping