Pancreatic islets, insulin produced

IDDM is caused by T cell-mediated autoimmune destruction of the insulin-producing P-pancreatic islet cells in genetically predisposed individuals. This is probably due to the expression of a super antigen on the surface of the jS cells in such individuals, although the molecular detail of what extent factors trigger onset of the jS cell destruction remain to be elucidated. IDDM may, however, be controlled by parenteral administration of exogenous insulin preparations, usually by regular s.c. injection. 

Initial experiments in the 1970s using inbred strains of rats illustrated the feasibility of this approach. Insulin-producing pancreatic islet cells donated by one set of rats were transplanted into other rats of the same strain, first made diabetic by injection with drugs such as streptozotocin, which destroy the pancreatic B cells. 

In their report the researchers describe a culturing technique that can turn mouse embryonic stem cells into cell clusters that resemble pancreatic islets. The clusters inner cells produced insulin, while outer cells produced glucagon and somatostatin, two other proteins typically synthesized by pancreatic cells. Most important, the embryonic stem cell-derived pancreas cells produce insulin in response to glucose, the fundamental role of beta cells that regulate insulin secretion. The major shortcoming of the system at this time is the low levels of insulin production. Refinements in culture technique or drug manipulation may be needed to achieve therapeutic levels. 

The insulin producing P cells of the pancreas are selectively destroyed by alloxan, which is reduced there to dialurate. Isolated pancreatic islets of mice were protected against the action of alloxan, by BESOD, by catalase, and by scavengers of OH radicals. A treatment of rat pancreatic islets with SOD, catalase or diethylenetriaminepenta-acetate attenuated the effect of alloxan, suggesting again a participation of OH radicals... 

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... 

The pancreatic islets consist of four primary cell types alpha (A) cells, which produce glucagon beta (B) cells, which produce insulin delta (D) cells, which produce somatostatin and (F) cells, which produce pancreatic polypeptide. As previously mentioned, this chapter focuses on the functions of insulin and glucagon. The exact physiologic roles of the other pancreatic hormones are not entirely clear. For example, the function of the pancreatic polypeptide released from pancreatic F cells remains to be determined. 

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. 

The similarity to glucagon and the location of secretion of these peptides suggested that they may be part of the enteroinsular axis, a hormonal system producing intestinal factors (incretins) in response to nutrients which influence the release of pancreatic hormones [124], While GLP-1 and GLP-2 have no or little activity on hormone release from the pancreas, the truncated peptides GLP-l(7-37) and GLP-1 (7-36)-NH2 have potent glu-eose-dependent insulinotropic effects in the rat perfused pancreas [125-127] and in insulin-producing islet cell lines [128, 129]. In addition, GLP-1 (7-37) stimulates proinsulin synthesis, an important additional effect since it may then allow the constant replenishing of insulin stores and make exhaustion... 

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