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Potential of correlative light and electron microscopy for understanding Diabetes Type 1

Posted by Vera Lanskaya on Feb 19, 2018 11:59:04 AM

Diabetes Type 1, one of the two widely spread forms, is an autoimmune decease, which is caused by destruction of insulin-producing beta cells in pancreas. This type of Diabetes is called insulin-dependent: the body’s immune system attacks the beta cells located in the Islets of Langerhans in the pancreas, which normally maintain the blood sugar levels by producing the necessary amount of insulin. When the islets do not release the insulin, the amount of glucose in the blood builds up. This results in cells suffering and dying from the lack of glucose and high blood sugar levels, which makes multiple organs collapse and lead to coma and death.

This type of diabetes is considered to be one of the most heritable common diseases [1]. Another important role in the pathogenesis is played by environmental factors. It is estimated that 9% of the population is affected by this life-threatening decease [2]. Despite the intensive research efforts over the past years, the exact causes of the decease are still unknown.

A better understanding of this form of Diabetes could be obtained from a rigorous study of the islets of Langerhans. This can be done by imaging them with an electron microscope (EM), a technique commonly applied in life sciences. The main advantage of EM, with transmission electron microscopy (TEM) or more recently with scanning electron microscopy (SEM), is the high spatial resolution achievable, which allows the identification of subcellular features. The disadvantage of this technique, however, is its speed: it takes a long time to acquire the images with a good signal-to-noise ratio. Additionally, identifying the cells only by the structure and form can be extremely laborious. What helps is to have a technique that can identify cells over a large field of view. This is achieved by fluorescence microscopy (FM).

The combination of both techniques in one integrated system is called Simultaneous Correlative Light and Electron Microscopy (SCLEM). It simultaneously allows the identification of cells on the basis of their function and reveals the structural details at high resolution. The SECOM is therefore a powerful tool to study the complex relation between form and function in biology.

The Islets of Langerhans were imaged using the SECOM system integrated with an SEM. Healthy rat pancreas was used as a sample. A customized protocol developed for SCLEM imaging was followed, and a thin section of the sample was then imaged in the SECOM. The images were acquired using an automated overlay procedure.

Islets of langerhans on DELMIC SECOM

Figure 1: Simultaneously acquired correlative image of the islets of Langerhans imaged on the Delmic SECOM integrated with an FEI Verios 460 Scanning Electron Microscope. Sample courtesy: B.N.G. Giepmans & P. de Boer, UMCG.

As it can be seen from the image, the labelling of the insulin (beta cells) in orange with Alexa Fluor 594 is clearly visible and the ultrastructure can be examined in detail from the EM contrast. The image also shows the guanine quadruplexes and the nucleus. These results demonstrate the potential of CLEM for studying Diabetes Type 1.

If you are interested in learning more about this research, we invite you to download the application note: Type 1 diabetes: Imaging insights.


If you would like to know more about the possibilities of SECOM for studying biological processes, join us for the iCLEM workshop at MPI Bremen on 8th of March. You read more about it and register by clicking on the button below. 

Register for iCLEM workshop



[1] Wang, Z., Xie, Z., Lu, Q. et al. Clinic Rev Allerg Immunol (2017) 52: 273.

[2] G. Danaei et al., The Lancet 378, 9785, 31-40 (2011)

Topics: correlative microscopy, life sciences, SECOM, clem, correlative light electron microscope