The 1921 discovery of insulin was a Big Bang from which a vast and expanding universe of research into insulin action and resistance has issued. In the intervening century, some discoveries have ma...

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Mechanisms of Insulin Action and Insulin Resistance

Cultured human lymphocytes and rat hepatoma cells were labeled with [32P]orthophosphate and the insulin receptor subunits identified by immunoprecipitation and sodium dodecyl sulfate-gel electrophoreses. In both cell types the 95,000-dalton (beta) subunit of the insulin receptor was selectively phosphorylated. Phosphorylation was specifically stimulated by insulin in a dose-dependent fashion after 1 and 15 minutes of hormone treatment, whereas human growth hormone was without effect. This phosphorylation may be a very early event in insulin action.

https://science.sciencemag.org/content/sci/215/4529/185.full.pdf

Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor

Chronic (5-16 hr) exposure of cultured human lymphocytes to 10-8 M insulin at 37° in vitro produced a decrease in insulin receptor concentrations unaccounted for by simple occupancy of sites; acute exposure (0-2 hr) was without effect. These results reproduced observations in vivo where chronic hyperinsulinemia (e.g., 10-8 M insulin in the circulation of obese insulinresistant hyperglycemic mice) is associated with a substantial reduction in the concentration of insulin receptors per cell, while acute hyperinsulinemia in vivo has no effect on receptor concentration. These data suggest a reciprocal relationship between insulin in the extracellular fluid and the concentration of insulin receptors per cell, which is mediated at the target cell itself by intracellular insulin-sensitive regulatory processes and directly affects target-cell sensitivity to hormone.

https://www.pnas.org/content/pnas/71/1/84.full.pdf

Insulin-Dependent Regulation of Insulin Receptor Concentrations: A Direct Demonstration in Cell Culture

Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin.

Publisher Summary This chapter reviews the physical, chemical, and biological properties of insulin in the light of the atomic arrangement found in insulin crystals. It also describes the relation of the three-dimensional arrangement of the atoms in the molecule of 2-zinc insulin crystal to the solution properties of insulin (particularly its states of aggregation), to the chemical reaction and chemical modification of the molecule, and to its primary biological activity. Normally the insulin crystals contain two zinc ions to every six molecules of insulin—a hexamer. The slow solution of the crystals provides a method of delaying the action of insulin that closely parallels the methods adopted in the pancreas itself for the storage and release of insulin. Within many β granules, grains can be seen that almost certainly contain zinc insulin hexamers packed in a crystalline array, and in experimental animals diabetes has been induced by chelating agents, such as EDTA, perhaps simply by interfering with normal insulin storage. It, therefore, seems plausible that ready crystallization of insulin in the presence of zinc is a reflection of the storage processes in the β cell.

Insulin: The Structure in the Crystal and its Reflection in Chemistry and Biology by

The relationship between the insulin-binding capacity of fat cells and the cellular response to insulin. Studies with intact and trypsin-treated fat cells.

Frances W. Barham

Papers

The relationship between the insulin-binding capacity of fat cells and the cellular response to insulin. Studies with intact and trypsin-treated fat cells.

Effects of Insulin on the Levels of Adenosine 3':5'-Monophosphate and Lipolysis in Isolated Rat Epididymal Fat Cells

Insulin-like effects of trypsin on fat cells. Localization of the metabolic steps and the cellular site affected by the enzyme.

A water fountain for decontamination of used vials and test tubes.