The β-cell is receptive to intricate hormonal, neuronal and nutrient signaling which is key for normal physiology but complicates the study of specific effects of individual factors on β-cell function. To preserve the microenvironment of the β-cell, most studies of β-cell physiology have been performed on in vitro cultured islets of Langerhans. However, whereas islets in the pancreas are highly vascularized and oxygenated, ischemic conditions cannot be avoided in the center of cultured isolated islets, leading to abnormal islet cell function and viability. Moreover, in the absence of blood flow, intercellular communication in islets is likely to change as well. Furthermore, contamination of islets with anatomically associated acinar cells is inevitable during isolation and may have a major influence on the specificity of experiments.