Insulin therapy pancreas

Treatment of type 1 DM requires providing exogenous insulin to replace the endogenous loss of insulin from the non-functional pancreas. Ideal insulin therapy mimics normal insulin physiology. 

Type 1 diabetes is characterized by a near-absolute insulin deficiency at diagnosis or soon thereafter. The beta cells of the pancreas are no longer able to secrete insulin due to autoimmune destruction. Therefore, people with type 1 diabetes require exogenous administration of insulin for survival. People with type 2 diabetes may require insulin therapy when diet, exercise, and the oral agents are no longer enough to provide adequate glucose control. 

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

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). 

This approach was effective in that it expressed IL-4 pancreas specifically, without any side-effects from the systemic expression of IL-4. These results also indicated that autoim-mune diabetes in NOD mice is not a systemic disease, and it can be modulated from the islet compartment. Therefore, for somatic gene therapy, the rat insulin pro-moter was inserted upstream of the IL-4cDNA (Lee et al., 2001a). This plasmid, pRIP-mIL-4 was complexed with water soluble lipopolymer and transfected in vitro. The results indicated that pRIP-mIL-4 expressed IL-4 cell-type specifically. 

As mentioned in Chapter 1, perhaps the purest form of drug therapy is the replacement of inadequate amounts of an endogenous substance such as a hormone. Any gland that normally secretes a hormone is a potential target for hypofunctioning. Classical examples include Addison s disease (adrenal cortex), dwarfism (anterior pituitary), juvenile-onset insulin-dependent diabetes (pancreas), and hypothyroidism (thyroid). 

For the first time in history there was clear, unambiguous clinical evidence, in humans, that symptoms of diabetes mellitus could be controlled with the exogenous administration of the active factor of the pancreas—insulin. Thus, replacement therapy with the newly discovered hormone, insulin, had arrested what was clearly an otherwise fatal metabolic disorder. From that point forward, diabetes mellitus (type 1) became a manageable disease by pharmacological intervention. 

Insulin is isolated from beef and pork pancreas. However, human insulin is replacing the animal hormone for therapy. Human insulin is produced by a special strain of Escherichia coli that has been genetically altered to contain the gene for human insulin. Pork insulin is closest in structure to human insulin, differing by only one amino acid. 

Diabetes mellitus (DM) is an increasingly common disease of sugar metabolism. Juvenile-onset diabetes, also known as Type I or insulin-dependent diabetes (IDDM), is an autoimmune disease that results in decreased release of insulin by the pancreas. Late-onset diabetes, also known as Type II or non-insulin-dependent diabetes (NIDDM), results from reduced sensitivity of cells to the insulin signal. A convenient animal model for studying diabetes and testing alternative therapies is the streptozotocin-freated diabetic rat. Streptozotocin (STZ) attacks the pancreas and decreases insulin production and release, thus, mimicking many aspects of the human disease. Since insulin is not orally absorbed, the oral administration of vanadium compounds that are insuhn-mimetic or insulin-enhancing would be a very attractive therapy ... 

Insulin is secreted by the beta cells of the endocrine pancreas, and is responsible for the regulation of glucose utilization. Insulin deficiency is responsible for some forms of diabetes, where it is used in replacement therapy (Kahn and Shechter, 1990). 

In Type-I diabetes, which is due to the loss of insulin-producing cells as a consequence of autoimmune disorders, substitution of insulin is the most important measure. However, merely to inject one daily dose is not an adequate therapy. Here, the objective is to mimic the daily variations in plasma insulin which are closely related to food intake. One such attempt which has improved microvascular complications is intensified insulino-therapy through multiple daily injections of insulin. Another approach is to develop techniques of islet transplantation and using a bioartificial pancreas. In the case of islet transplantation, tissues will not only respond to changes in blood glucose levels but also to hormones of the entero-insular axis. 

Classification of diabetes mellitus Assessment of p-ceU activity Obtain insurance coverage for insulin pump Monitoring therapy Pancreatectomy Transplant (pancreas-islet cell)... 

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