A distinctively different distribution of hsp 60 proteins has been observed in p cells of islets infiltrated by mononuclear cells. The preferential association of hsp 60 antibodies with secretory granules was lost in stressed p cells, with a concomitant marked increase of hsp 60 immunoreactivity in the cytosol (65,8). Electron microscopy revealed that the cytosolic hsp 60 immunoreactivity was associated with p cell microvesicles and a microtubule-like network (Fig. 3 and 4). Polyclonal and monoclonal hsp 60 antibodies (anti-Pi and MAb PI) used in these studies were raised against hsp 60 protein PI (40,41,61). Interestingly, the PI protein has initially been discovered as a microtubule-related protein in mutants of Chinese hamster ovary cells (CHO) resistant to the microtubule inhibitor (60,66). In CHO cells, it appeared in roughly equimolar amounts with tubulin.
The redistribution of hsp 60 in P cells of prediabetic NOD mice appeared to be consequence of insulitis. Progression of insulitis from nondestructive, peri-islet to destructive, intraislet insulitis was associated with a gradual reduction of hsp 60 antibody binding to secretory granules and increased binding to the cytosol (65).
The redistribution was accompanied by pathological changes in cell morphology. The changes which occurred in inflamed islets included an increased number of mitochondria, swelling of mitochondria and secretory granules, an increased number of microvesicles, fragmentation of the Golgi apparatus, and the collapse of the intermediate filament cytoskeleton. The latter was judged indirectly, being based on the alteration in secretory function of p cells and secretory granule biogenesis (65).
Based on these data, we have postulated that the hsp 60 redistribution is a part of the general p cell response to stress caused by islet inflammation. In this context, the reason for an appearance of hsp 60 immunoreactivity associated with microvesicles and p cell microtubules could be a practical one directed to restore cellular trafficking and the collapsed cytoskeleton. On the other hand, elevated cytoplasmic levels of hsp 60 might be used as an indicator of cellular stress.
In view of the strong immunogenicity of hsp 60 proteins, the emerging question was whether altered distribution of hsp 60 would change the antigenicity of p cells and evoke autoimmune responses in diabetes-prone mice.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...