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Diabetologia
Published in: Diabetologia 1/2011

01-01-2011 | Letter

The beta and alpha cell-specific Znt8-knockout mouse model: new mechanistic insights?

Authors: M. El Muayed, W. L. Lowe Jr

Published in: Diabetologia | Issue 1/2011

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Excerpt

To the Editor: One of the most intriguing aspects of the recent article by Wijesekara at al. [1] is their experiments designed to elucidate the mechanism underlying impairment of beta cell function in the setting of decreased activity of the zinc transporter 8 (ZnT8, transcription product of the Znt8 gene, also known as Slc30a8). The authors report increased proinsulin relative to insulin in the islets and serum of beta cell-specific Znt8-knockout mice. They attribute this observation to a decrease in abundance of components of the insulin-processing machinery, namely prohormone convertase 1 and 2, as well as carboxypeptidase E. …
Literature
1.
Wijesekara N, Dai FF, Hardy AB et al (2010) Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia 53:1656–1668CrossRefPubMed
2.
Kambe T, Narita H, Yamaguchi-Iwai Y et al (2002) Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic beta cells. J Biol Chem 277:19049–19055CrossRefPubMed
3.
Nicolson TJ, Bellomo EA, Wijesekara N et al (2009) Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes 58:2070–2083CrossRefPubMed
4.
El Muayed M, Billings LK, Raja MR et al (2010) Acute cytokine mediated downregulation of the zinc transporter ZnT8 alters pancreatic beta cell function. J Endocrinol 206:159–169CrossRefPubMed
5.
Huang XF, Arvan P (1995) Intracellular transport of proinsulin in pancreatic beta-cells. Structural maturation probed by disulfide accessibility. J Biol Chem 270:20417–20423CrossRefPubMed
6.
Lemaire K, Ravier MA, Schraenen A et al (2009) Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci USA 106:14872–14877CrossRefPubMed
7.
Rutter GA (2009) Think zinc: new roles for zinc in the control of insulin secretion. Islets 2:49–50CrossRef
8.
Murgia C, Devirgiliis C, Mancini E, Donadel G, Zalewski P, Perozzi G (2009) Diabetes-linked zinc transporter ZnT8 is a homodimeric protein expressed by distinct rodent endocrine cell types in the pancreas and other glands. Nutr Metab Cardiovasc Dis 19:431–439CrossRefPubMed
Metadata
Title
The beta and alpha cell-specific Znt8-knockout mouse model: new mechanistic insights?
Authors
M. El Muayed
W. L. Lowe Jr
Publication date
01-01-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 1/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-010-1934-2

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