Research Highlights

Here are a few SRP Diabetes research highlights presented.

Lifestyle factors and epigenetics

New important insights by which lifestyle factors may affect metabolism through epigenetically altering how DNA is read has been reported by Zierath et al. This may help explain the effects of exercise and obesity on insulin sensitivity in type 2 diabetes.

Barres, R., Kirchner, H., Rasmussen, M., Yan, J., Kantor, Francisc R., Krook, A., Näslund, E., Zierath, Juleen R. Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation. Cell Reports 2013 3, 1020-1027.

Barrès R, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, Caidahl K, Krook A, O'Gorman DJ, Zierath JR. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 2012 Mar 7;15(3):405-11.


Novel protein makes muscles bigger and stronger

In a study in mice, SRP Diabetes scientist and American scientists have identified a previously unknown protein that spurs muscle growth and increased power following resistance exercise – such as bodybuilding or weightlifting. The findings are presented in the journal Cell, and the scientists speculate that artificially raising the novel protein's levels might someday help prevent muscle mass loss caused by, for example, cancer, prolonged inactivity in hospital patients, and aging.

Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC, Greene NP, Wu J, Estall JL, Irving BA, Lanza IR, Rasbach KA, Okutsu M, Nair KS, Yan Z, Leinwand LA, Spiegelman BM. A PGC-1α Isoform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy. Cell. 2012. 151: 1319-1331.


Fat turnover in humans

Detailed information on fat turnover in humans was achieved by groups of Arner and Spalding, indicating that not only calorie intake, but metabolic alterations of fat cells markedly contribute to obesity.

Arner P, Bernard S, Salehpour M, Possnert G, Leibl J, Steier P, Buchholz BA, Eriksson M, Arner E, Hauner H, Skurk T, Ryden M, Frayn KN, Spalding KL Dynamics of human adipose lipid turnover in health and metabolic disease Nature. 2011 478 (7367), 110-113


Gene behind unhealthy adipose tissue identified

SRP Diabets researchers have for the first time identified a gene driving the development of pernicious adipose tissue in humans. The findings imply, which are published in the scientific journal Cell Metabolism, that the gene may constitute a risk factor promoting the development of insulin resistance and type 2 diabetes.

Gao H, Mejhert N, Fretz JA, Arner E, Lorente-Cebrián S, Ehrlund A, Dahlman-Wright K, Gong X, Strömblad S, Douagi I, Laurencikiene J, Dahlman I, DaubCO, Rydén M, Horowitz MC, Arner P. Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue. Cell Metab. 2014 Jun 3;19(6):981-92.


An adipokine that improves beta cell function

SRP Diabetes researchers have together with colleagues at Harvard discovered that adipsin, a cell signaling protein made by fat cells, plays a critical, previously unsuspected role in stimulating insulin secretion to control blood sugar.  This might be the long-sought molecule linking fat tissue metabolism to pancreatic beta cell function.

Lo JC, Ljubicic S, Leibiger B, Kern M, Leibiger IB, Moede T, Kelly ME, Chatterjee Bhowmick D, Murano I, Cohen P, Banks AS, Khandekar MJ, Dietrich A, Flier JS, Cinti S, Blüher M, Danial NN, Berggren PO, Spiegelman BM. Adipsin Is an Adipokine that Improves β Cell Function in Diabetes. Cell. 2014 Jul 3;158(1):41-53


Studying islets in vivo in the eye

The development of the unique methodology for studying Langerhans islets in vivo by the group of Berggren has yielded important insights into the biology and pathology of both rodent and human islets. The insights are relevant to both type 1 and type 2 diabetes. This unique methodology has also opened up new possibilities for islet transplantation in patients.

E Ilegems, A Dicker, S Speier, A Sharma, A Bahow, P Karlsson Edlund, IB Leibiger & P-O Berggren. Reporter islets in the eye reveal the plasticity of the endocrine pancreas. PNAS. 2013; Online 18-22 November

Rodriguez-Diaz R, R Dando, MC Jacques-Silva, A Fachado, J Molina, M Abdulreda, C Ricordi, SD Roper, P-O Berggren & A Caicedo. Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming human beta cell function. Nature Medicine, 2011:17, 888-892

Perez VL, A Caicedo, DM Berman, E Arrieta, MH Abdulreda, R Rodriguez-Diaz, A Pileggi, E Hernandez, SR Dubovy, JM Parel, C Ricordi, NM Kenyon, NS Kenyon & P-O Berggren. The anterior chamber of the eye as a clinical transplantation site for the treatment of diabetes. Diabetologia. 2011: 54, 1121-1126


Type 2 diabetes associated gene Ide

Novel functional data on the type 2 diabetes associated gene Ide has revealed an unexpected role for this gene in insulin secretion and beta cell survival, as reported by the group of Edlund.

Steneberg, P., Bernardo, L., Edfalk, S., Backlund, F., Lundberg, L., Östenson, C.G., and Edlund, H. The type 2 diabetes associated gene Ide is required for insulin secretion and suppression of α-synuclein levels in β-cells. Diabetes. 2013; 62: 2004-2014


Human genetics studies on vascular complications in diabetes

Contributions to large-scale human genetics studies by the Hamsten group have provided a better understanding of vascular complications in diabetes patients. These results support the clinical practice of treating diabetic dyslipidemia by targeting triglyceride levels rather than cholesterol.

Global Lipids Genetics Consortium, Willer CJ, et al (including Hamsten A). Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013 Nov;45(11):1274-83.

Do R, Willer CJ, Schmidt EM, et al (includingh Hamsten A) Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet. 2013 Nov;45(11):1345-52.