Beta cell, loss

As indicated earlier, most cases of type 1 diabetes are caused by an autoimmune response that selectively attacks and destroys pancreatic beta cells in susceptible individuals. Therefore, drugs that suppress this autoimmune response may be helpful in limiting beta cell destruction, thereby decreasing the severity of this disease.4,41 Several immunosuppressants have been investigated as a way to potentially minimize beta cell loss from the autoimmune reactions underlying type 1 diabetes some immunosuppressants that have been considered for this situation include cyclosporine, azathioprine, cyclophosphamide, methotrexate, and glucocorticoids.11 The pharmacology of these immunosuppressants is discussed in more detail in Chapter 37. 

Silva, J. P., Kohler, M., Graff, C., Oldfors, A., Magnuson, M. A., Berggren, P. O., and Larsson, N. G., Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat. Genet. 26,336—340 (2000). 

Incretin mimetics are an exciting development, because when used alone they do not promote hypoglycemia, as their actions on insulin and glucagon are strictly glucose dependent. They are accompanied by weight loss, and they may preserve beta cell mass. 

Type 1 diabetes is due to autoimmune destruction of pancreatic islet beta cells causing loss of insulin. Type 2 diabetes is due to the combination of cellular resistance to insulin and beta cell failure. Tissue lesions are common to both types of diabetes, and chronic hyperglycemia (or a closely related metabolic abnormality) is responsible for diabetic complications including diabetic nephropathy. 

Corbett NJ, Gabbott PL, Klementiev B, Davies HA, Colyer FM, Novikova T et al (2013) Amyloid-Beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimetic peptide. PLoS One 8 e71479. doi 10.1371/journal. pone.0071479... 

Diabetes mellitus type 1 (T1D). Autoimmune form of diabetes mellitus caused by immune-mediated destruction of insulin-producing beta cells in the pancreas with irreversible loss of insulin production. Islet cell autoantibodies and autoantibodies directed against glutamic acid decarboxylase, insulin, and the IA2-antigen are diagnostic markers for T1D as well as risk markers for the development of this disease. 

In particular, loss of first-phase insulin secretion seems to be the first and most important defect of the beta cell. In the UKPDS, the decline in insulin secretion was strongly associated with disease progression [6]. In Pima Indians, development of diabetes mellitus was associated with only a modest deterioration in insulin sensitivity, but a major decrease in acute insulin response to glucose [7]. In addition, loss of first-phase insulin secretion has been shown to be a predictor of impaired glucose tolerance in the San Antonio Heart Study [8]. 

Proliferation of the eosinophilic adenoma leads to compression and atrophy of some of the other cellular components of the hypophysis, particularly the beta cells, with loss of gonadal function in men and amenorrhea in women. Sexual atrophy can be relieved by the administration of estrogens and androgens. In general, sex hormone administration relieves such subjective symptoms as headache, insomnia, irritability, lassitude, numbness, and stinging of the hands. It is not known whether the sex hormones compensate for the reduced gonadostimulin secretion or if they directly counteract the exaggerated somatotropin production. 

A crude extract of E. globulus leaves rich in phenolic glycoside(s) has been reported to have antihyperglycemic activity in rabbits a loss of this activity resulted upon purification of this material. Oral administration of an aqueous extract of eucalyptus to streptozoto-cin-treated mice resulted in a reduction of hyperglycemia and weight loss. The same extract enhanced in vitro insulin secretion from a pancreatic beta-cell line after 20 min incubation at a concentration of 0.25-0.5 mg/mL. ... 

The aorta from one of the juvenile diabetic monkeys age 4-1/2 years is shown in Fig. 5. Clinical history showed a marked loss in the ability to respond to an IV-GTT and less fasted IRI although fasted glucose, triglyceride, and prebetalipoprotein concentrations were normal. At necropsy the pancreas beta cells appeared normal but contained only about half the normal complement of beta granules. The glucose mismanagement and lack of lipid Increases were probably minimal and lasted for such a short period of time that no sudanophilia or lesions appeared in the aorta. Some medial... 

Fig. 7. Aorta from a monkey classed as normal but which had occasional hyperglycemia and some loss of beta cells in the isles of Langerhans...

This particular monkey had a normal IV-GTT and adequate IRI, but necropsy showed about a 30% loss of the beta cells of the isles of Langerhans. Aortas from the other two monkeys categorized as clinically normal had 10 to 30% sudanophilic blush, 5 to 25% of raised roughened areas and streaks, but only a few small discrete lesions. The pancreatic isles of Langerhans had some beta granule loss in one case and 40% loss of beta cells in the other. 

I. This condition results from complete loss of the pancreatic beta cells... 

Blood sugar (blood glucose) in human beings is controlled by the secretion of (—>) insulin by the beta (B- or (3-) cells of the islands of Langerhans in the pancreas. Loss of insulin synthesis leads to (—>) diabetes. Type 1 diabetes (insulin dependent diabetes mellitus, EDDM) begins in juveniles as an organ-specific autoimmune reaction, the destructive insulitis. 

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