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Insulin resistance is a hallmark of type 2 diabetes, and many insights into the functions of insulin have been gained through the study of mice lacking the IR. To gain a better understanding of the role of insulin action in the brain versus peripheral tissues, we created 2 mouse models with inducible IR inactivation, 1 in all tissues including brain ([IR.sup.[DELTA]wb]), and 1 restricted to peripheral tissues ([IR.sup.[DELTA]per]). While downregulation of IR expression resulted in severe hyperinsulinemia in both models, hyperglycemia was more pronounced in [IR.sup.[DELTA]wb] mice. Both strains displayed a dramatic upregulation of hepatic leptin receptor expression, while only [IR.sup.[DELTA]per] mice displayed increased hepatic Stat3 phosphorylation and Il6 expression. Despite a similar reduction in IR expression in white adipose tissue (WAT) mass in both models, [IR.sup.[DELTA]wb] mice had a more pronounced reduction in WAT mass and severe hypoleptinemia. Leptin replacement restored hepatic Stat3 phosphorylation and normalized glucose metabolism in these mice, indicating that alterations in glucose metabolism occur largely as a consequence of lipoathrophy upon body-wide IR deletion. Moreover, chronic intracerebroventricular insulin treatment of control mice increased fat mass, fat cell size, and adipose tissue lipoprotein lipase expression, indicating that CNS insulin action promotes lipogenesis. These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation., Introduction Resistance to the biological effects of the peptide hormone insulin represents one of the hallmarks during the development of type 2 diabetes (1), (2). Apart from the direct effect [...]

Surface IgA1-bearing B lymphocytes are purified from human blood for molecular and cellular examination through the application of high-gradient magnetic cell sorting. In normal physiological conditions, switch recombination deletion of DNA seems to have been channeled to IgA1. It is evident for both immunoglobulin heavy-chain gene loci.