ABSTRACT
Type 2 diabetes mellitus (DM2) is characterized metabolically by defects in both insulin secretion and insulin action, resulting in hyperglycemia. Histopathologically, DM2 is characterized by depositions of protein in the pancreatic islets. This 'islet amyloid' is present in >90% of patients with DM2, as well as in monkeys and cats with DM2. The pathogenesis of DM2 is heterogeneous and multifactorial, although insulin resistance seems to be the predominant initiating factor for development of the disease. In the longer term, an insulin secretion defect is also revealed (referred to as 'beta-cell failure'), resulting in clinically manifest diabetes. Recent data, particularly from transgenic mouse studies, indicate that islet amyloidosis is a diabetogenic factor, which is both consequence (of insulin resistance) and cause (of beta-cell failure) of DM2. Available transgenic mouse models with islet amyloid formation in vivo will provide the opportunity to assess the effectiveness of novel anti-amyloidogenic therapies, for which promising results are emerging.
Subject(s)
Amyloid/metabolism , Diabetes Mellitus, Type 2/metabolism , Islets of Langerhans/metabolism , Amino Acid Sequence , Amyloid/chemistry , Amyloid/genetics , Animals , Diabetes Mellitus, Type 2/etiology , Humans , Islet Amyloid Polypeptide , Mice , Mice, Transgenic , Molecular Sequence Data , Protein Structure, Secondary , Sequence AlignmentABSTRACT
Biochemical markers improve the classification and staging of breast cancer and may refine management decisions if it can be shown that they correlate with accepted prognostic factors or patient outcome. Using phosphorus-31 magnetic resonance spectroscopy ((31)P MRS), we determined the phospholipid content of 43 malignant breast tumors, correlating the profiles with specific histopathologic and clinical features and hormone receptor status. Among the 14 phospholipids identified, the mean mole percentage of sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, and alkylacylphosphatidylcholine predicted cellular infiltration, infiltration type, elastosis, lymphatic invasion, perineural invasion, necrosis, and estrogen receptor positivity. (31)P MRS phospholipid profile data provide statistical correlations among histologic features and molecules known to play important roles in cellular communication, regulation, and processes unique to malignant tissues.
