Beta cell regeneration

Beta cells have traditionally been viewed as long lived cells having a low replication potential. With this, the potential for their regeneration following the autoimmune destruction in type 1 diabetes was considered to be unlikely. However, several recent lines of evidence indicate that the regenerative capability of the endocrine pancreas is potentially higher than previously thought. Indeed, age appears to be an influential factor (i.e., the younger the age, the greater the potential for replication; especially in those under the age of 10), while other factors (e.g., pregnancy, obesity, pancreatitis) also support the potential for beta cell replication.

Adult beta cells are long lived cells

Mitotic figures are exceedingly rare in the adult human pancreas, although replication is relatively high in early fetal life, it diminishes exponentially after birth and reaches near-zero values in young adults. The apparent absence of neoformation led to the concept that beta cells, like neurons, are long-living cells that last for many years and perhaps even a life-time; provided that they are not destroyed by an autoimmune process noted for type 1 diabetes. This concept is supported by recent estimates of beta cell life span, using a quantification of cytoplasmic lipofuscin inclusions that are known to increase linearly with age. Using this approach, it has been calculated that 97% of beta cells are established by the age of twenty [1]. This finding is in line with other approaches using 14C carbon dating and thymidine analogue incorporation [2].

Adult beta cells retain a potential for increased replication

Although beta cells are only rarely found to divide, especially in those above the age of 10[3], frequent mitotic figures have been reported in individual case studies of non-diabetic adult patients with, amongst others, acute liver disease. Moreover, high levels of beta cell replication, reaching levels normally only found in the early fetal pancreas, were observed in the pancreas of young-adult patients on extended life support (fig 1) and in the inflamed islets of an autoantibody-positive individual [4]. These findings support the idea that beta cells retain a substantial capacity for replication, but are only induced in doing so under specific clinical conditions that need to be analyzed in more detail.

Fig 1 Replicating islet cells (Ki67-brown) in the pancreas of a 19 year old male organ donor on prolonged life support. Endocrine cells are stained in red.
Fig 1 Replicating islet cells (Ki67-brown) in the pancreas of a 19 year old male organ donor on prolonged life support. Endocrine cells are stained in red.

References

  1. ^ Cnop M, Igoillo-Esteve M, Hughes SJ, Walker JN, Cnop I, Clark A. Longevity of human islet alpa and beta cells. Diabetes, Obesity and Metabolism 13 (suppl1):39-46, 2011.

  2. ^ In’t Veld P, De Munck N, Van Belle K, Buelens N, Ling Z, Weets I, Haentjens P, Pipeleers-Marichal M, Gorus F, Pipeleers D. Beta cell replication is increased in donor organs from young patients after prolonged life support. Diabetes 59: 1702-1708, 2010.

  3. ^ Gregg BE, Moore PC, Demozay D, Hall BA, Li M, Husain A, Wright AJ, Atkinson MA, Rhodes CJ.J Clin Endocrinol Metab. 2012 Jun 28. [Epub ahead of print]

  4. ^ Perl S, Kushner JA, Buchholz BA, Meeker AK, Stein GM, Hsieh M, Kirby M, Pechhold S, Liu EH, Harlan DM, Tisdale JF. J Clin Endocrinol Metab. 2010 Oct;95(10):E234-9. Epub 2010 Jul 21.

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