Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited.
The present review draws attention to the diversity of islet lesions seen in human type 1 and type 2 diabetes. This heterogeneity of islet changes is best demonstrated by immunocytochemistry. In type 1 diabetes the endocrine pancreas is characterized by selective loss of B cells, which most likely results from a slowly acting autoimmune process depending on the presence of both genetic and environmental factors. The process starts years before overt diabetes develops and manifests when the B-cell volume is reduced by about 80%. In type 2 diabetes B cells are always present, regardless of the duration and severity of the disease, but lack any signs of functional activity. This reflects a secretory defect of the B cells which obviously becomes evident under the conditions of obesity, hyperinsulinism and insulin resistance. Obese but non-diabetic subjects show, in parallel to their hyperinsulinism, an increased B cell volume, suggesting that under prediabetic conditions the B cells have still the capacity to respond to increased functional demands by enhanced proliferation. In manifest diabetes the B cells have lost their proliferative potential. Whether this is due to an inherent defect or the consequence of a functional disturbance, is not clear. The development of islet amyloidosis most likely represents an associated functional abnormality of the B cell.
D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology*
D007328:Insulin; D005934:Glucagon