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Type 2 diabetes and lipotoxicity

Principal investigator; Holm, Cecilia, Professor,

Clinical speciality:

Phone: ++46462228581

Co-workers, Lund University: Axling Ulrika, Berger Karin, Jones Helena

Research area/areas: Cell and Molecular Biology, Endocrinology and Diabetes, Nutrition and Dietetics

Free fatty acids, derived mainly from the large triglyceride stores in adipose tissue, are the quantitatively most important fuel in mammals. Fatty acids also constitute signaling molecules in a variety of cell types, e.g. a lipid-derived signal appears to be necessary for stimulus-secretion coupling in pancreatic beta-cells and fatty acid derivatives are ligands for a group of nuclear receptors, i.e. the peroxisome-proliferator activated receptors (PPARs). In agreement with this dual role of fatty acids, most cell types contain small triglyceride stores, from which fatty acids can be mobilized through the action hormone-sensitive lipase (HSL) and possibly other lipases. Lipid abnormalities may be the primary pathogenetic factor in the development of insulin resistance and insulin secretion defects, the two hallmarks of type 2 diabetes, with excessive storage of triglycerides in non-adipose cells as the common precipitating event.

The project can be divided into four major parts. The first part involves studies into the role of HSL in adipogenesis and adipose expansion. In the second part mechanisms underlying islet dysfunction are elucidated. The third part focuses on adiponutrin, a variant of which has been shown to be strongly associated to liver steatosis. Structural, functional and regulatory aspects of adiponutrin are investigated. The fourth part involves exploiting functional foods with beneficial effects in relation to insulin resistance and type 2 diabetes.

The project increases the understanding of the mechanisms underlying development of lipid metabolism disorders, in particular diabetes and obesity, and may provide new concepts for prevention/intervention in these diseases.

Link to project homepage: http://www.cmb.lu.se/lu_molsign/MEG

5 recent original publications

Mulder, H., Sörhede Winzell, M., Contreras, J.A., Fex, M., Ström, K., Ploug, T., Galbo, H., Arner, P., Lundberg, C., Sundler, F., Ahrén, B. and Holm, C.
Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.
J. Biol. Chem.. 2003; 278: 36380-36388

Sörhede Winzell, M., Svensson, H., Enerbäck, S., Ravnskjaer, K., Mandrup, S., Esser, V., Arner, P., Alves-Guerra, MC., Miroux, B., Sundler, F., Ahrén, B. and Holm, C.
Pancreatic beta-cell liptoxicity induced by overexpression of hormone-sensitive lipase.
Diabetes. 2003; 52: 2057-2065

Mulder, H., Sörhede Winzell, M., Contreras, J.A., Fex, M., Ström, K., Ploug, T., Galbo, H., Arner, P., Lundberg, C., Sundler, F., Ahrén, B. and Holm, C.
Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.
J. Biol. Chem.. 2003; 278: 36380-36388

Ström Kristoffer, Gundersen Thomas E, Hansson Ola, Lucas Stephanie, Fernandez Celine, Blomhoff Rune, Holm Cecilia
Hormone-sensitive lipase (HSL) is also a retinyl ester hydrolase: evidence from mice lacking HSL.
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2009; 23: 2307 - 2316

Andersson Ulrika, Berger Karin, Högberg A, Landin-Olsson Mona, Holm Cecilia
Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind, cross-over investigation in obese persons.
European journal of clinical nutrition. 2011; Dec 14: -

Further publications here (new window)

Financing/year