Beta cells, islet destruction

More direct interference with glucose metabolism cannot be excluded. Interferon alfa can reduce the sensitivity of peripheral tissues or liver to insulin and accelerate the destruction of stimulated pancreatic beta-cells (540,541) this could be a possible mechanism in patients not exhibiting islet cell antibodies. This is also in keeping with rare instances of induction or exacerbation of type II noninsulin dependent diabetes mellitus (SEDA-19, 335). 

Insulin-dependent diabetes mellitus (IDDM) is an example of a metabolic disease under active consideration for inducible gene therapy strategies. In this disorder, inflammatory cytokines have been shown to activate apoptosis in pancreatic beta cells. Experimental studies indicate that expression of insulinlike growth factor-1 (IGF-1) can prevent the cytokine-mediated destruction of beta cells of the pancreas (Giannoukakis et al., 2001). Regulated expression of IGF-1 in human pancreatic islets, to preserve beta cell function, may be a useful approach in the treatment of certain types of diabetes (Demeterco and Levine, 2001). 

Rabinovitch, A., Suarez-Pinzon, W., Strynadka, K., Ju, Q. D., Edelstein, D., Brownlee, M., Korbutt, G. S. and Rajotte, R. V. (1999). Transfection of human pancreatic islets with an anti-apoptotic gene (bcl-2) protects beta-cells from cytokine-induced destruction. Diabetes 48,... 

Smith, D. K., Korbutt, G. S., Suarez-Pinzon, W. L., Kao, D., Rajotte, R. V. and Elliott, J. F. (1997). Interleukin-4 or interleukin-10 expressed from adenovirus-transduced syngeneic islet grafts fails to prevent beta cell destruction in diabetic NOD mice. Transplantation 64, 1040-1049. 

Wogensen, L., Lee, M. S. and Sarvetnick, N. (1994). Production of interleukin 10 by islet cells accelerates immune-mediated destruction of beta cells in nonobese diabetic mice. J. Exp. Med. 179, 1379-1384. 

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. 

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. 

Much has been learned about insulin because of its relationship with diabetes. In classical, type I diabetes (or insulin-dependent diabetes), the individual does not make insulin, or at least not enough of it. This is usually caused by destruction of the beta cells of the islets of Langerhans in the pancreas from a type of autoimmune disease. The only remedy for type I diabetes is regular insulin injections, and insulin is produced for this purpose by recombinant DNA technology (Chapter 13). 

Rabinovitch A, Suarez-Pinzon WL. Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus. Biochem Pharmacol 1998 55(8) 1139-ll49. 

In the 1920 s when pure preparations of insulin were difficult to obtain, some preparations for intravenous administration were shown to contain a hyperglycemic factor that was later named glucagon. The factor was purified from insulin preparations and crystallized in 1953. Glucagon is a straight chain polypeptide hormone composed of 29 amino acids and devoid of disulfide bonds. It is elaborated in the alpha cells of the islet of the pancreas and is extractable from pancreas after beta cell destruction. 

Suarez Pinzon, WL, Strynadka, K and Rabinovitch, A (1996) Destruction of rat pancreatic islet beta-cells by cytokines involves the production of cytotoxic aldehydes. Endocrinology,... 

Streptozocin En+, G+, H+, M+, R++ Destroys pancreatic beta islet cells may produce acute diabetes mellitus. Niacinamide (see p 475) may be effective in preventing islet cell destruction. Renal toxicity in two-thirds of patients. 

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