Klari Noormets "The development of diabetes mellitus, fertility and energy metabolism disturbances in a Wfs1-deficient mouse model of Wolfram syndrome"

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View all other units

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Date:

22.10.2014 - 13:00 to 15:00

Supervisors:
Professor Vallo Tillmann, University of Tartu
Professor Sulev Kõks, University of Tartu

Thesis supervisors:
Professor Timothy Barrett, University of Birmingham, United Kingdom

Summary:
Wolfram syndrome (WS) is an autosomal recessive disorder usually diagnosed in childhood when non-autoimmune type I diabetes occurs with optic atrophy, cranial diabetes insipidus and sensorineural deafness. Also dilated renal outflow tracts, multiple neurological abnormalities and various neurological and psychiatric disorders can be present. The reason for WS is the mutation in the WFS1 gene. The exact mechanism of the development of the diabetes related to the WS is yet not known. Some data has shown that the onset of diabetes tends to occur earlier in boys than in girls. As yet there has been no data regarding the fertility of patients with WS. Previous studies have described anterior pituitary dysfunction and, in male patients, the presence of primary gonadal atrophy and hypergonadotropic hypogonadism. As far as we know, the role of the Wfs1 gene in fertility, as well as in thyroid function and in energy metabolism, has not been studied.

The aim of the study was to describe the development of the diabetes, fertility and energy metabolism disturbances in an animal model of WS - Wfs1-deficient mouse.

We showed that the fertility of male mutant mice is impaired and the reasons for that are the morphological changes in the testes and sperm. Sperm motility is not affected in Wfs1KO mice.

There are severe sex-related differences in the development of growth failure and diabetes. Growth failure in male Wfs1KO mice is already present from birth, whereas in females it develops during the first months of life. Severe glucose intolerance developed in both sexes, but overt diabetes with low plasma insulin levels occurs only in male Wfs1KO mice. One of the reasons for developing WS related diabetes is not the insulin deficiency itself, but the impairment in converting proinsulin to active insulin.

The energy metabolism did not differ significantly between Wfs1 KO and wt mice. Our data also suggest some degree of leptin resistance in female Wfs1KO mice, which needs to be confirmed in further studies.

Location:

Prof A. Linkberg Lecture Theatre (Puusepa 8)

URL:

hdl.handle.net/10062/43589

Event category:

Defence

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Klari Noormets "The development of diabetes mellitus, fertility and energy metabolism disturbances in a Wfs1-deficient mouse model of Wolfram syndrome"

September