Abstract

Modern omics techniques reveal molecular structures and cellular networks of tissues and cells in unprecedented detail. Recent advances in single cell analysis have further revolutionized all disciplines in cellular and molecular biology. These methods have also been employed in current investigations on the structure and function of insulin secreting beta cells under normal and pathological conditions that lead to an impaired glucose tolerance and type 2 diabetes. Proteomic and transcriptomic analyses have pointed to significant alterations in protein expression and function in beta cells exposed to diabetes like conditions (e.g., high glucose and/or saturated fatty acids levels). These nutritional overload stressful conditions are often defined as glucolipotoxic due to the progressive damage they cause to the cells. Our recent studies on the rat insulinoma-derived INS-1E beta cell line point to differential effects of such conditions in the phospholipid bilayers in beta cells. This review focuses on confocal microscopy-based detection of these profound alterations in the plasma membrane and membranes of insulin granules and lipid droplets in single beta cells under such nutritional load conditions.

Highlights

  • The composition of phospholipids in biological membranes determines their cell barrier and cellular communication functions as well as subcellular organelles structure and functions.These properties are determined by the nature of the various phospholipid species and the availability of free fatty acids (FFA) from cellular metabolism and the diet

  • This is of paramount consequence upon exposure of beta cells to high levels of SFA that ensues alone, or in combination with high glucose levels, an array oflipotoxic effects that often contribute to the decline in the mass and function of beta cells in islets of Langerhans [17,18,19,20]

  • This study aims at integrating these findings with standard lipidomics analyses to follow lipid turnover single beta cells and in their subcellular organelles and compartments

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Summary

Introduction

The composition of phospholipids in biological membranes determines their cell barrier and cellular communication functions as well as subcellular organelles structure and functions. In addition to the inherent composition of phospholipids and their turnover in subcellular organelles in beta cells, it is important to emphasize the critical role of increased availability of dietary (essential and non-essential) FFA and their incorporation into phospholipids This is of paramount consequence upon exposure of beta cells to high levels of SFA (e.g., palmitic acid) that ensues alone, or in combination with high glucose levels, an array of (gluco)lipotoxic effects that often contribute to the decline in the mass and function of beta cells in islets of Langerhans [17,18,19,20]. This study aims at integrating these findings with standard lipidomics analyses to follow lipid turnover single beta cells and in their subcellular organelles and compartments

Phospholipid Turnover in Cells
Lipidomic Analyses of Beta Cells
Impact of palmitic acid on fatty acid abundance in phospholipids
Confocal Imaging-Based Fluidity and Micropolarity Maps of Single Beta Cells
Generalized
Summary
Conclusions

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