Analysis of Beta-cell metabolism - Metabolomics

To enhance understanding of metabolism and mitochondrial function in beta-cells, analysis of metabolism must be improved. Until now, metabolites have routinely been examined one-at-a-time, using established biochemical techniques. This does not take into account that changes in many metabolic pathways occur simultaneously. Some metabolic changes may escape detection if pathways were not deliberately examined.

To overcome these limitations of traditional biochemistry, we are employing an approach where we can examine metabolism either in an unbiased, global fashion or in a more targeted way. The former is sometimes referred to as metabolomics, while the latter is termed metabolite profiling. In metabolomics one makes use of advanced statistical measures to transform the large data sets so that they can be interpreted. In metabolite profiling, we strive to produce quantitative or semi-quantitative data on specific metabolites. In metabolomics analysis, patterns, clusters or signatures are given to illustrate the biological changes in a metabolic system.   

In these studies, metabolites in a sample must first be separated, followed by identification. For many years, we have employed gas chromatography to separate metabolites. The peaks of the resulting chromatogram are then identified by concomitant mass spectrometry. Levels of the metabolites can be semi-quantitatively determined by measuring the areas of identified peaks. Recently, we have established a new platform for metabolomics analyses. It takes advantage of liquid chromatography, and permits greatly enhanced sensitivity. Importantly, unknown metabolites can more readily be identified by the new instrument.

The approach is applied to clonal insulin-producing beta-cells, rodent and human islets as well as blood plasma. The cells are kept under different conditions. Metabolites are extracted from the cells and subjected to metabolomics analysis.  This way, we have developed a method to identify pathways which are activated or disturbed under different conditions, for instance stimulatory and unstimulatory glucose concentrations, or in diabetes.

Peter Spegel and Arslan Ali

Staff

The metabolomics platform is supervised by Associate Professor Dr Peter Spégel. He is an analytical chemist specialized in separation techniques and metabolomics approaches. He is aided by Lotta E. Andersson, who is biotechnologist, pursuing her Ph.D. under the supervision of Dr. Spégel, and Dr Arslan Ali, an Erasmus Fellow from Pakistan.

Read more

Spégel P, Sharoyko VV, Göhring I, Danielsson AP, Malmgren S, Nagorny CL, Andersson LE, Koeck T, SHarp GW, Straub SG, Wollheim CB, Mulder H. Time-resloved metabolomics analysis of beta-cells implicates the pentose phosphate pathway in the control of insulin release. Biochem J 450:595-605, 2013.

Spégel P, Ekholm E, Tuomi T, Groop L, Mulder H, Filipsson K. Metabolite profiling reveals normal metabolic control in carriers of mutations in the glucokinase gene (MODY2). Diabetes 62:653-61, 2013.

Last updated: February 28, 2014
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