The subunit structure of the insulin receptor and molecular interactions with major histocompatibility complex antigens

Insulin receptors were labeled with 125I-photoreactive insulin (specifically labeling alpha-subunits) and by insulin-stimulated autophosphorylation (specifically labeling beta-subunits). The results show that the insulin receptor exists under different free and disulfide-linked combinations of alpha and beta subunits. Moreover, the insulin receptor is closely associated to class I antigens of the major histocompatibility complex to form a high molecular weight multi-molecular membrane complex.     

Amiloride blocks cell-free protein synthesis at levels attained inside cultured rat hepatocytes

Amiloride, a passive Na⁺ influx inhibitor, lowers initial rates and plateau levels of [³⁵S]met uptake into proteins in cell-free rabbit reticulocyte lysates (ID₅₀∽0.4 mM). Isolated hepatocytes take up amiloride through a saturable (K_m∽0.02 mM; V_max∽1.43 nmol/ 10⁶ cells/min) Na⁺-dependent process. Similar temperature dependent uptake occurs in cultured hepatocyte monolayers. In chemically defined media, under growth reinitiation conditions, amiloride lowers overall rates of cellular protein and albumin synthesis (ID₅₀∽0.4 and ∽0.028 mM, respectively). Amiloride concentrations (0.02 mM) that half-maximally inhibit reinitiation of hepatocyte DNA synthesis reach, within 30 min, cellular levels (∽0.14 mM) that block reticulocyte lysate protein synthesis by 25%. These findings complicate interpretations, from studies in many eukaryotic systems, of cause and effect between mitogen-activated membrane Na⁺ influxes and the reinitiation of DNA synthesis.     

Insulin receptor internalization and recycling: mechanism and significance

Using a 125I-photoreactive insulin analogue that can be covalently coupled to its receptor we have shown that in rat hepatocytes the insulin receptor is concomitantly internalized with the labeled hormone and afterwards is progressively recycled back to the cell surface. In the course of the internalization process the insulin-receptor complex associates with clear vesicles and later on with lysosomes from which it is recycled through clear vesicles. On the basis of these observations it is suggested that modulation of the rates of internalization and of recycling of the insulin receptor can regulate the number of available surface insulin receptors. This hypothesis is supported by the results of experiments showing that monensin, an inhibitor of receptor recycling enhances insulin induced loss of its own surface receptors (down regulation) in U-937 monocytes.     

Insulin receptors in rat brain: insulin stimulates phosphorylation of its receptor beta-subunit

In rat brain cortex synaptosomes insulin stimulated the phosphorylation of its own receptor beta-subunit (94 kDa) as identified by immunoprecipitation with anti-insulin or anti-receptor antiserum. The receptor alpha-subunit (115 kDa) was characterized by specific labeling with 125I-labeled photoreactive insulin. These observations indicate that: (i) insulin receptors in brain are composed of alpha-subunits which bind insulin, and beta-subunits, the phosphorylation of which can be stimulated by insulin; (ii) the size of alpha-subunits in brain is significantly smaller than in other tissues (115 vs 130 kDa), whereas beta-subunits (94 kDa) are identical. We suggest that brain insulin receptors represent a subtype regarding their binding function, whereas their enzyme function is more conserved.     

Socioecology Explains Individual Variation in Urban Space Use in Response to Management in Cape Chacma Baboons (Papio ursinus)

International Journal of Primatology - The presence of wildlife adjacent to and within urban spaces is a growing phenomenon globally. When wildlife’s presence in urban spaces has negative...