Diabetes mellitus islet cells

Another condition involving ceruloplasmin is aceru-loplasminemia. in this genetic disorder, levels of ceruloplasmin are very low and consequently its ferroxidase activity is markedly deficient. This leads to failure of release of iron from cells, and iron accumulates in certain brain cells, hepatocytes, and pancreatic islet cells. Affected individuals show severe neurologic signs and have diabetes mellitus. Use of a chelating agent or administration of plasma or ceruloplasmin concentrate may be beneficial. 

CF-related diabetes shares characteristics of both type 1 and type 2 diabetes mellitus but is categorized separately. The primary cause of CFRD is insulin deficiency resulting from both reduced functional pancreatic islet cells and increased islet amyloid deposition. Insulin secretion is delayed in response to glucose challenge, and absolute insulin secretion over time is reduced. Some insulin resistance may also be present in CFRD however, sensitivity may be increased in CF patients without diabetes.8... 

The origins of diabetes mellitus are still being investigated. There is a familial trait—certain histocompatability phenotypes and perhaps other non-HLA genes are more frequently displayed by juvenile diabetics than others. Viral infections in childhood may precipitate immune responses which damage the P islet cells. Other types of diabetes, such as that shown by middle-aged or older patients, have different causes and can often be controlled by appropriate diet. 

Figure 3.20 A plot of the percentage of maximal activity of glucokinase and hexokinase against the glucose concentration. Hexokinase is present in most if not all cells. Glucokinase is only present in hepatocytes and p-cells of the Islets of Langerhans in the pancreas (known as the endocrine pancreas). The enzyme is physiologically very important in both tissues e.g. a low activity in the p-cells can be a cause of one type of diabetes mellitus.

The pathogenesis of type I diabetes is autoimmune destruction of the cells of the pancreas. The factor or factors that trigger this autoimmune response are unknown. Predisposing factors appear to include certain major histocompatibility complex haplotypes and autoantibodies to various islet cell antigens. The progression of the autoimmune response is characterized by lymphocytic infiltration and destruction of the pancreatic cells resulting in insulin deficiency. Type I diabetes mellitus constitutes about 10% of cases of diabetes mellitus. 

Over 5% of the population of western nations is afflicted with diabetes. TTie most prevalent form of diabetes, non-insulin-dependent diabetes mellitus (NIDDM, or type 11), is commonly associated with obesity and hypertension, and is believed to be the consequence of altered insulin action or insulin secretion (for review see Defronzo, 1988 Defronzo and Ferrannini, 1991). Insulin-dependent diabetes mellitus (IDDM, or type 1 diabetes) accounts for approximately 10% of all cases of diabetes. IDDM is characterized by specific destruction of insulin secreting /3-cells found in islets of Langerhans. Destruction of 80-90% of islet /3-cells causes insulin deficiency and the inability to regulate blood glucose levels. 

Since its isolation in 1921, insulin has been the object of an enormous amount of experimentation aimed at clarifying its mode of action. It is produced by the P cells of the pancreatic islets of Langerhans and released into the bloodstream in response to elevated glucose levels. Tire absence of insulin or of a normal response to insulin results in the condition of diabetes mellitus, which is the most prevalent human metabolic disorder (see Box 17-G).343... 

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). 

In patients with chronic hepatic B or C the respective prevalences of pancreatic autoantibodies increased from 2% and 3% at baseline to 5% and 7% after interferon (544). In all, 31 published cases of type 1 diabetes mellitus attributed to interferon alfa treatment were detailed, mostly in patients with hepatitis C. Irreversible diabetes required permanent insulin treatment in all but eight cases. At least one marker of pancreatic autoimmunity was positive in nine of 18 patients before treatment, and in 23 of 30 patients at the onset of diabetes. In accordance with these results and the likelihood of a genetic predisposition, the authors recommended screening for islet cell and glutamic acid decarboxylase autoantibodies before and during interferon alfa treatment. However, owing to the low number of reported cases and the paucity of studies that have examined the relation between pancreatic autoimmunity and the occurrence of diabetes, further research on the predictive potential of such a systematic investigation is warranted. 

Lohmann T, List C, Lamesch P, Kohlhaw K, Wenzke M, Schwarz C, Richter O, Hauss J, Seissler J. Diabetes mellitus and islet cell specific autoimmunity as adverse effects of immunsuppressive therapy by FK506/tacrolimus. Exp Clin Endocrinol Diabetes 2000 108(5) 347-52. 

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). 

A relatively new approach in treating diabetes mellitus is the transplantation of tissues containing pancreatic beta cells into patients with this disease.73,109 For example, islet tissues containing functioning beta cells can be harvested from adult, neonatal, or fetal pancreatic... 

The islet cells of the pancreas synthesize and secrete insulin and glucagon. These hormones are important in regulating glucose uptake and use, as well as in other aspects of energy metabolism. Problems in the production and effects of insulin are typical of a disease known as diabetes mellitus. Diabetes mellitus can be categorized into two primary forms type 1 diabetes, which is caused by an absolute deficiency of insulin, and type 2 diabetes, which is caused by a decrease in peripheral insulin effects, combined with abnormal insulin release. 

Replacement of deficient gene products or even of organs is also utilized in the treatment of genetic disorders for example, replacement of coagulation factor VIII in hemophilia A, of or-antitrypsin in persons deficient in this factor or of pancreatic islet cells in some forms of diabetes mellitus. 

Interleukin-1, pancreatic P cells, and insulin-dependent diabetes mellitus Insulin-dependent diabetes mellitus is an autoimmune disease that causes the gradual destruction of insulin-producing pancreatic P cells. It has been postulated that the infiltration of macrophages into the pancreatic islets plays a key role in the destruction of P cells and that cytokines, especially interleukin-1, which is released locally from macrophages, may be the toxic molecule causing this destruction. 

Loweth et al. [120] showed that fluoride induces apoptosis in clonal pancreatic fi cells and in the cells of normal rat islets of Langerhans. The process may reflect the formation of AlF41 since it was inhibited by the aluminum chelator desferrioxamine. Recent studies provide evidence that apoptosis of pancreatic fi cells is important in the early etiology of diabetes mellitus. Treating thymus lobe cells with aluminofluoride complexes also provoked apoptosis of a wider range of thymocyte subtypes [121] with an accumulation of inositol phosphates. The responses to aluminofluoride complexes were not prevented by inhibitors of tyrosine kinases, suggesting that unidentified G-proteins which couple to phospholipase C activation may also be capable of initiating apoptosis by a route independent of the T cell receptor. 

In this case, which was marked by three autoimmune complications (insulin-dependent diabetes mellitus, myositis, and myasthenia gravis) in a single patient, a retrospective analysis of the patient s serum before aldesleukin therapy showed the presence of antibodies against glutamic acid decarboxylase, insulin, islet cell antigen, and striated muscle, but was negative for acetylcholine receptor antibodies. Immune stimulation by aldesleukin was... 

Glucagon, which is produced in the alpha cells of the islets of Langerhans, is used in diabetes mellitus type 1 to stimulate glucose output from the liver during hypoglycemia (1 mg subcutaneously, repeated once or twice) when glucose cannot be given intravenously. In some countries... 

Srikanta, S., Ganda, O., Eisenbarth, G. S., and Soeldner, J. S. (1983). Islet-cell antibodies and beta-cell function in monozygotic triplets and twins initially discordant for type I diabetes mellitus. N. Engl.. Med. 308,322-325. 

Diabetes mellitus, which is due to a deficiency of insulin or the resistance of tissues to its action, results in hyperglycemia. Autoimmunity may play a role in the etiology of insulin-dependent diabetes mellitus. In this condition, the plasma contains antibodies to islet cells of the pancreas, including the p cells that produce insulin. 

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