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Horm Metab Res 2012; 44(06): 471-475
DOI: 10.1055/s-0032-1301920
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Evidence for a Role of Frataxin in Pancreatic Islets Isolated from Multi-Organ Donors with and Without Type 2 Diabetes Mellitus

S. Del Guerra
1   Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, Pisa University Hospital, Pisa, Italy
,
V. D’Aleo
1   Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, Pisa University Hospital, Pisa, Italy
,
G. Gualtierotti
1   Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, Pisa University Hospital, Pisa, Italy
,
R. Pandolfi
1   Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, Pisa University Hospital, Pisa, Italy
,
U. Boggi
2   Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy
,
F. Vistoli
2   Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy
,
S. Barnini
3   Department of Experimental Pathology, Medical Biotechnology, Infectious Diseases and Epidemiology, Pisa University Hospital, Pisa, Italy
,
F. Filipponi
4   Department of Liver Transplantation, Hepatology, and Infectious Diseases, Division of General Surgery and Liver Transplantation, Pisa University Hospital, Pisa, Italy
,
S. Del Prato
1   Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, Pisa University Hospital, Pisa, Italy
,
R. Lupi
5   Department of Medical Area, Section of Metabolic Diseases and Diabetes, Pisa University Hospital, Pisa, Italy
› Author Affiliations
Further Information

Publication History

received 23 May 2011

accepted after second revision 12 January 2012

Publication Date:
07 March 2012 (online)

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Abstract

Frataxin (FXN) is a mitochondrial protein involved in iron metabolism and in the modulation of reactive oxygen and/or nitrogen species production. No information is currently available as for the role of frataxin in isolated human pancreatic islets. We studied islets from pancreases of multi-organ donors with (T2DM) and without (Ctrl) Type 2 diabetes mellitus. In these islets, we determined FXN gene and protein expression by qualitative and quantitative Real-Time RT-PCR, nitrotyrosine concentration, and insulin release in response to glucose stimulation (SI). FXN gene and protein were expressed in human islets, though the level of expression was much lower in T2DM islets. The latter also had lower insulin release and higher concentration of nitrotyrosine. A positive correlation was apparent between SI and FXN gene expression, while a negative correlation was found between nitrotyrosine islet concentration and FXN expression. Transfection of Ctrl islets with siRNA FXN caused reduction of FXN expression, increase of nitrotyrosine concentration, and reduction of insulin release. In conclusion, in human pancreatic islets FXN contributes to regulation of oxidative stress and insulin release in response to glucose. In islets from T2DM patients FXN expression is reduced while oxidative stress is increased and insulin release in response to glucose impaired.

Key words

human pancreatic islet - β-cell - oxidative stress - frataxin - type 2 diabetes
 

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