engleski

ROLE OF AMYLIN IN PANCREATIC beta-CELL DEATH: A POTENTIAL KILLER OR JUST AN INNOCENT WITNESS?

Amylin is a 37-amino acid peptide, which is produced by pancreatic islet â-cells and co-secreted with insulin in response to nutrient stimuli. Studies have demonstrated that amylin is the key protein component of amyloid deposits found in the islets of Langerhans in almost all patients with non-insulin-dependent diabetes mellitus (NIDDM). A particular region of the peptide between positions 20 and 29, termed the amyloidogenic sequence, is thought to be responsible for amyloid fibril formation by the human peptide. The sequence of human amylin is identical in those with NIDDM and non-affected individuals, and the mechanism of amyloid deposition in diabetes remains unclear at present. Furthermore, islet amyloid formation is not found in diabetic rats, whose amylin molecule has a different amino acid sequence in this molecular region. Evidence suggests that amyloid formation may be related to hypersecretion of amylin associated with hyperglycemia acting in conjunction with other unknown factors which may enhance pancreatic fibril formation. Possible roles for amylin in the pathogenesis of diabetes have been suggested. Amylin has been implicated in insulin resistance and abnormal insulin secretion, both of which are characteristic of NIDDM. The inhibitory effects of amylin on glycogen synthesis in isolated skeletal muscles have also been reported. In addition, a number of studies have suggested that human amylin may be toxic to islet â-cells. New findings regarding the role of human amylin in â-cell death and the mechanism of its cytotoxicity will be discussed.

pancreatic beta-cells; diabetes mellitus; amylin; cell death

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