Nesfatin-1 stimulates insulin secretion, inhibits glucagon secretion and is expressed in human and rodent beta cells

Voss, U., Riva, M., Dekker Nitert, M. N., Ling, C., Lindqvist, A. and Wierup, N. (2010). Nesfatin-1 stimulates insulin secretion, inhibits glucagon secretion and is expressed in human and rodent beta cells. In: 46th EASD Annual Meeting of the European Association for the Study of Diabetes: Abstracts. 46th Annual Meeting of the European Association for the Study of Diabetes (EASD), Stockholm, Sweden, (S222-S222). 20-24 September 2010. doi:10.1007/s00125-010-1872-z


Author Voss, U.
Riva, M.
Dekker Nitert, M. N.
Ling, C.
Lindqvist, A.
Wierup, N.
Title of paper Nesfatin-1 stimulates insulin secretion, inhibits glucagon secretion and is expressed in human and rodent beta cells
Conference name 46th Annual Meeting of the European Association for the Study of Diabetes (EASD)
Conference location Stockholm, Sweden
Conference dates 20-24 September 2010
Proceedings title 46th EASD Annual Meeting of the European Association for the Study of Diabetes: Abstracts   Check publisher's open access policy
Journal name Diabetologia   Check publisher's open access policy
Place of Publication Heidelberg, Germany
Publisher Springer
Publication Year 2010
Sub-type Published abstract
DOI 10.1007/s00125-010-1872-z
ISSN 0012-186X
1432-0428
Volume 53
Issue Supp. 1
Start page S222
End page S222
Total pages 1
Language eng
Formatted Abstract/Summary
Background and aims: Nesfatin-1 is a recently discovered regulatory peptide
with anorexigenic properties. The peptide is the N-terminal part of nucleobindin
2 (NUCB2) and is highly expressed in brain areas known to regulate
feeding behaviour. Outside the brain, nesfatin-1 expression has been reported
in gastric endocrine cells. We studied the possibility of nesfatin-1 expression
in human, rat, and mouse islets of Langerhans using immunocytochemistry
and in situ hybridization. Furthermore, we investigated potential influence of
nesfatin-1 on secretion of insulin and glucagon. Effects of nesfatin-1 on Ca2+
and cAMP levels was studied in INS-1 (832/32) cells, and nesfatin-1 gene
expression in human islets under glucolipotoxic conditions was examined
using affymetrix.
Materials and methods: Nesfatin-1 expression was examined using immunocytochemistry,
in situ hybridization. Insulin and glucagon secretion after
1h static incubations of isolated mouse islets was analyzed with RIA or ELISA.
Ca2+ fluorescence and cAMP was studied in INS-1 (832/13) cells.
Results: Nesfatin-1 was found to be highly expressed in human islets. Double
staining for nesfatin-1 and the main islet hormones revealed that nesfatin-1
was exclusively expressed in human beta cells. Nesfatin-1 was also highly expressed
in rat and mouse islets. The majority of all nesfatin-1 expressing cells
were beta cells in rat and mouse. In the rat a minor subpopulation of the alpha
cells harbored also nesfatin-1. Importantly, in situ hybridization and microarray
for NUCB2 mRNA confirmed the immunocytochemical data. Studies
in isolated mouse islets revealed that nesfatin-1 stimulates insulin secretion
at both low (2.8 mM and 5.5mM, p<0.001) and high glucose concentrations
(11.1. mM, p<0.001). Nesfatin-1 also augmented forskolin-enhanced glucose-
stimulated insulin secretion (GSIS) (p<0.01), but not GSIS potentiated
by carbachol or KCl. In addition, nesfatin-1 lowered secretion of glucagon at
low (2.8 and 5.5 mM) glucose (p<0.001), but not at high (11.1 mM) glucose.
Further, nesfatin-1 caused an increase in Ca2+ influx, but decreased cAMP
in INS-1 (832/13) cells. Moreover, affymetric analysis revealed that NUCB2
mRNA was moderately upregulated under glucolipotoxic conditions in human
islets.
Conclusion: Together our data suggest that nesfatin-1 is a novel glucose-lowering
peptide in human and rodent islets. In view of these data, stimulation
of the nesfatin-1 pathway could be a new treatment strategy for Type 2 diabetes.
Keyword Nesfatin-1
Glucose-lowering peptide
Type 2 diabetes
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Abstract number: 458.

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