Insulin producing cells

Welsh, N., 1996, Interleukin-l-induced ceramide and diacylglycerol generation may lead to activation of the c-Jun NH2-terminal kinase and the transcription factor ATF2 in the insulin-producing cell fine RINm5F. J. Biol. Chem. 271 8307-8312. 

HORMONES OF THERAPEUTIC INTEREST 321 Treating diabetics with insulin-producing cells... 

Eizirik, D. L., Cagliero, E., Bjorklund, A., and Welsh, N. (1992a). Interleukin-1)3 induces the expression of an isofortn of nitric oxide synthase in insulin-producing cells, which is similar to that observed in activated macrophages. FEBS Lett. 308, 249-252. 

There are ethical considerations in the use of stem cells for research and therapy. ESCs have been derived from the ICM of human embryos (hECSs) [18]. hESCs are derived from leftover frozen embryos, created for in vitro fertilization, destined to be discarded. Because it involves the destruction of embryos, there is a debate over the use of hESCs for research and therapy. On one hand, there are scientific reports and evidence that ESCs, including hESCs, differentiate into various cell types of the body, such as neuronal and insulin producing cells [19], backing the scientific claim of the potential of ESCs for therapy. On the other hand, opponents of the use of hESCs for research and therapy argue that it is morally unacceptable to destroy human life. The scientific and ethical debate over the use of hESCs for research and therapy considerably slows stem cell research. 

Soria B, Roche E, ReigJA, Martin F. Generation of insulin-producing cells from stem cells. Novartis Found Symp. 2005 265 158-167. 

Tiedge, M., Lortz, S., Drinkgern, J. and Lenzen, S. (1997). Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 46, 1733-1742. 

Bedoya, F.J., M. Flodstrom, and D.L. Eizirik (1995). Pyrrolidine dithiocarbamate prevents IL-1-induced nitric oxide synthase mRNA, but not superoxide dismutase mRNA, in insulin producing cells. Biochem. Biophys. Res. Comm. 210 816-821. 

In people diagnosed with type 1 diabetes, the cells of the pancreas that normally produce insulin are destroyed by the patient s own immune system. New studies indicate that it may be possible to direct the differentiation of cultured embryonic stem cells to form insulin-producing cells in the patient s own pancreas. 

Prior research has shown that both /3-cells and T-cells act to initiate type 1 diabetes. T-cells attack and destroy the insulin-producing /S-cells. /S-cells don t directly attack insulin-producing cells, but may trigger the T-cells to attack. Rituximab, a chimeric monoclonal antibody against CD20, found primarily on the surface of /S-cells, has shown potential in delaying the development of type 1 diabetes. 

The mechanism of action of GLP-l(7-37) and GLP-1 (7-36)-NH2 has been the subject of in vitro study. Both peptides increase c-AMP levels in insulin-producing cell lines in a dose-dependent manner [128, 141, 142] and functional receptors have been identified on insulin- and somatostatin-producing cell lines [142-144]. 

Similar to other tissues, insulin-producing cells possess an adenylate cyclase-cAMP system including stimulatory and inhibitory G-proteins and phosphodiesterases. 

As discussed above, protein phosphorylation caused by CaCaMk, PKA and PKC may induce a variety of functions in the machinery of stimulus-secretion coupling. This, however, implies that to keep the system functional for regulation, dephosphorylations must also take place. Dephosphorylations in general are the result of phosphatase activity. To date, little is known about the function of such phosphatases in insulin-producing cells, or whether they are regulated. 

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. 

Shiroi A, Yoshikawa M, Yokota H et al (2002) Identification of insulin-producing cells derived from embryonic stem cells by zincchelating dithizone. Stem Cells 20(4) 284-292... 

T2D is a serious disease which accounts for greater than 90% of all individuals with diabetes. Type 1 diabetes (T1D) is most frequently diagnosed in children as an autoimmune disease with nearly complete destruction of islet [3 cells - the insulin-producing cells of the pancreas. Without insulin, these children experience massive elevations in plasma glucose levels however, they are deprived of the use of glucose as a cellular fuel for normal metabolic functions, since insulin provides the biochemical... 

The pancreas is a large organ containing exocrine and endocrine tissue. The islets of Langerhans make up the endocrine part and contain cells that produce insulin, glucagon and somatostatin. Cells that produce glucagon (a-cells) and somatostatin (D-cells) are found peripherally in the islets while the predominant insulin producing cells (f)-cells) are found in the centre. 

Bigdeli, N., Niemann, A., Sandler, S., and Eizirik, D. L. (1994). Dissociation between interleukin-1 3-induced expression of mRNA for superoxide disrautase and nitric oxide synthase in insulin-producing cells. Biochem. Biophys. Res. Commun. 203, 1542-1547. 

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