PUBLICATION
SerpinB1 Promotes Pancreatic ? 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
-
- Cell Proliferation*
- Humans
- Serpins/physiology*
- Liver/metabolism
- Animals
- PubMed
- 26701651 Full text @ Cell Metab.
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