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Molecular Metabolism

Department of Clinical Sciences Malmö
Head: Hindrik Mulder

Overall aims
 

We are a dynamic research group aiming to understand why the pancreatic b-cells fail to produce adequate amounts of insulin to regulate whole body metabolism in type 2 diabetes (T2D).

The main focus of our research is to understand metabolic and endocrine control of islet hormone secretion. To this end, we have published a large body of work focusing on carbohydrate and lipid metabolism in islets, transcriptional and translational control of b-cell mitochondria, chronobiology in islets, islet autophagy and monoamine signaling in islets. Currently, we are actively pursuing the following research aims:

Investigate mitochondrial function and dysfunction in β-cells
Identify metabolomics signatures in metabolic health and disease
Unravel how monoaminergic signaling controls islet function in health and disease

Part of our ongoing projects have emanated from findings in genome wide association studies (GWAS), where genetic variants of, e.g., Transcription factor B1 mitochondrial (TFB1M) and the Melatonin receptor 1B (MTNR1B) have been robustly associated with T2D. This approach has enabled us to direct our efforts towards the (dys)function of genes that are causally linked to the development of the disease. 

To reach our goals, we use multiple cell systems and animal models to study islet function and whole body metabolism. Benchmarks in this work have been the development of an in-house metabolomics platform and cellular respiratory analyses. We are currently expanding our model systems to include human inducible pluripotent stem cells (hIPSC) derived from patients with distinct geno- and phenotypes. In these, we will use genome editing techniques to correct genetic variants associated with b-cell dysfunction.

Overall, our work holds promise to increase understanding of how T2D evolves. It is our hope that these efforts will benefit patients with T2D in the future.

Research highlights

Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes.Tuomi T, Nagorny CL, Singh P, Bennet H, Yu Q, Alenkvist I, Isomaa B, Östman B, Söderström J, Pesonen AK, Martikainen S, Räikkönen K, Forsén T, Hakaste L, Almgren P, Storm P, Asplund O, Shcherbina L, Fex M, Fadista J, Tengholm A, Wierup N, Groop L, Mulder H.

Cell Metab. 2016 Jun 14;23(6):1067-77. doi: 10.1016/j.cmet.2016.04.009.

PMID:27185156

Serotonin (5-HT) receptor 2b activation augments glucose-stimulated insulin secretion in human and mouse islets of Langerhans. Bennet H, Mollet IG, Balhuizen A, Medina A, Nagorny C, Bagge A, Fadista J, Ottosson-Laakso E, Vikman P, Dekker-Nitert M, Eliasson L, Wierup N, Artner I, Fex M. Diabetologia. 2016 Apr;59(4):744-54. doi: 10.1007/s00125-015-3847-6.

PMID:26733006

Characterization of stimulus-secretion coupling in the human pancreatic EndoC-βH1 beta cell line. Andersson LE, Valtat B, Bagge A, Sharoyko VV, Nicholls DG, Ravassard P, Scharfmann R, Spégel P, Mulder H.

PLoS One. 2015 Mar 24;10(3):e0120879. doi: 10.1371/journal.pone.0120879.

PMID:25803449

Inhibition of the malate-aspartate shuttle in mouse pancreatic islets abolishes glucagon secretion without affecting insulin secretion. Stamenkovic JA, Andersson LE, Adriaenssens AE, Bagge A, Sharoyko VV, Gribble F, Reimann F, Wollheim CB, Mulder H, Spégel P.

Biochem J. 2015 May 15;468(1):49-63. doi: 10.1042/BJ20140697.

PMID:25731850

Loss of TFB1M results in mitochondrial dysfunction that leads to impaired insulin secretion and diabetes. Sharoyko VV, Abels M, Sun J, Nicholas LM, Mollet IG, Stamenkovic JA, Göhring I, Malmgren S, Storm P, Fadista J, Spégel P, Metodiev MD, Larsson NG, Eliasson L, Wierup N, Mulder H. Hum Mol Genet. 2014 Nov 1;23(21):5733-49. doi: 10.1093/hmg/ddu288.

PMID:24916378

Interested in working with us?

Links to open positions:

Please contact: Hindrik Mulder (hindrik.mulder [at] med.lu.se) or Malin Fex (malin.fex [at] med.lu.se).

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00