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  • Title: Insulin receptors in normal and disease states.
    Author: Grunberger G, Taylor SI, Dons RF, Gorden P.
    Journal: Clin Endocrinol Metab; 1983 Mar; 12(1):191-219. PubMed ID: 6342876.
    Abstract:
    The binding of insulin to its receptor has been studied under various physiological and pathological conditions. Quantitative studies have involved human circulating cells such as monocytes and erythrocytes, adipocytes, placental cells, and cultured cells such as fibroblasts and transformed lymphocytes. In animals, other target tissues such as liver and muscle have been studied and correlated with the human studies. Various physiological conditions such as diurnal rhythm, diet, age, exercise and the menstrual cycle affect insulin binding; in addition, many drugs perturb the receptor interaction. Disease affecting the insulin receptor can be divided into five general categories: (1) Receptor regulation--this involves diseases characterized by hyper- or hypoinsulinaemia. Hyperinsulinaemia in the basal state usually leads to receptor 'down' regulation as seen in obesity, type II diabetes, acromegaly and islet cell tumours. Hypoinsulinaemia such as seen in anorexia nervosa or type I diabetes may lead to elevated binding. (2) Antireceptor antibodies--these immunoglobulins bind to the receptor and competitively inhibit insulin binding. They may act as agonists, antagonists or partial agonists. (3) Genetic diseases which produce fixed alterations in both freshly isolated and cultured cells. (4) Diseases of receptor specificity where insulin may bind with different affinity to its own receptor or related receptors such as receptors for insulin-like growth factors. (5) Disease of affinity modulation where physical factors such as pH, temperature, ions, etc. may modify binding. In this review, we have considered primarily abnormality in insulin receptor binding. There are numerous other functions of the receptor such as coupling and transmission of the biological signal. These mechanisms are frequently referred to as postreceptor events, but more properly should be referred to as postbinding events since the receptor subserves other functions in addition to recognition and binding of insulin. This article reviews the literature on insulin receptor binding under various physiologic and pathologic conditions. Quantitative studies have involved human circulating cells such as monocytes and erythrocytes, adipocytes, placental cells, and cultured cells such as fibroblasts and transformed lymphocytes. Insulin binding is affected by physiologic conditions such as diurnal rhythm, age, diet, exercise, and the menstrual cycle. In addition, many drugs disturb the receptor interaction. Oral contraceptives, for example, appear to abolish the normal variation in insulin binding during the menstrual cycle due to reduced receptor concentration. Diseases affecting the insulin receptor can be divided into 5 categories: 1) receptor regulation, including diseases characterized by hyper or hypoinsulinemia; 2) antireceptor antibodies that bind to the receptor and competitively inhibit binding; 3) genetic diseases that produce fixed alterations in both freshly isolated and cultured cells; 4) diseases of receptor specificity where insulin may bind with different affinity to its own receptor or related receptors; and 5) diseases of affinity modulation, where physical factors such as pH, temperature and ions modify binding.
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