Islet Regeneration Therapy

Targeting the Root Cause of Diabetes Diabetes is caused by deficiency of insulin—absolute,
in the case of T1 diabetes (T1DM) and relative, in people with T2 diabetes (T2DM). To cure both forms of diabetes requires restoration of normal insulin secretion, which for T1DM is the only requirement and for T2DM is required along with normalization of insulin sensitivity. Islet transplantation and other cell therapies are being pursued but, the most feasible approach may be to pharmacologically induce regeneration of insulin secreting tissue. Exsulin development is aimed at restoring insulin secretion in all insulin-requiring patients.

exsulin is the brand name for a synthetic 15 amino acid (108-114) portion of the patented naturally occurring 175-amino acid polypeptide, islet neogenesis associated protein (INGAP). INGAP is a member of the Reg family of proteins, which appear to be involved in gut organogenesis. INGAP has been implicated in various settings of endogenous pancreatic regeneration, and may also play an important role in maintaining beta cell function. Related Reg proteins are found across multiple mammalian species.

The Target—Islet Regeneration

It is now generally accepted that pancreatic islets, which contain the insulin-producing beta cells, are formed from progenitor cells within the pancreas normally and, at low levels, after being destroyed by autoimmune or metabolic injury. Evidence of islet regeneration has accumulated over the last 80 years, but controversy about the importance of islet progenitor cells in post-natal humans arose from some researchers’ reliance on results of studying rodents, which differ from humans in key ways. More recent studies of human islets have clearly demonstrated that in normal people, beta cell mass is maintained by ongoing regeneration from non-beta cells progenitors. Clear evidence of islet regeneration has been observed even in elderly normal people and T1 and T2 patients. The process of cellular differentiation for both embryologic development and post-natal maintenance of islets occurs in a sequence associated with multiple transcription factors and humeral agents. An understanding of this sequence of cellular differentiation affords potential strategies for pharmacologic induction of regeneration. Evidence suggests that the process of cellular differentiation for occurs in a sequence such as depicted at right.

///for health professionals

Islet Regeneration





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