Distinctions between islet neogenesis and β‐cell replication: Implications for reversal of Type 1 and 2 diabetes

Abstract

The terms “islet” and “β‐cell” are often used interchangeably, yet islets are highly complex multicellular organelles that contain the insulin‐producing β‐cells and four other cells types, all of which play a role in maintaining glucose homeostasis within a very narrow range. Although the formation of new islets in adults is rare, occurring primarily in response to pancreatic injury and major stress to the pancreas, β‐cell replication from existing cells occurs throughout adulthood. An understanding of the regulatory factors controlling pancreatic development has more clearly defined the differences between new islet formation from progenitor cells located throughout the adult pancreas and β‐cell replication occurring within existing islets. The present review sets forth to more clearly distinguish the differences between the postnatal pathways of islet neogenesis and β‐cell replication with a discussion of the potential implications for reversal of Type 1 and 2 diabetic patients using islet neogenesis agents that are now in development. For Type 1 diabetic patients, an immune tolerance agent in conjunction with an islet neogenesis agent may allow achievement of adequate islet mass, perhaps with subsequent potential to withdraw medications. For Type 2 diabetic patients, lifestyle changes and/or medications may sustain the production of new islets and limit the accelerated β‐cell apoptosis characteristic of the condition.

Effect of moderate and high intensity chronic exercise on the pancreatic islet morphometry in healthy rats: BDNF receptor participation

“…In humans is about 50-60% while in rodents reaches 80%, 4 therefore, alterations of b-cells directly affect the islet area. Mechanisms such as b-cell neogenesis (differentiation from precursor cells), b-cell proliferation and transdiferentiation, and b-cell hypertrophy are responsible for b-cell mass increase; 5,6,7,8,9 while, b-cell reduction is determined by apoptosis and b-cell atrophy. 5,7 Studies in obese or diabetic rodent models have shown that exercise counter-regulates the IRS2-PI3K-pAkt growth pathway attenuated in Langerhans islet resulting in a bigger b cell area, major b cell proliferation rate and lower apoptosis.…”

The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes

“…Current T1D management includes insulin therapy and pancreas or islet cell transplantation; however, none of these procedures will ensure the complete removal of diabetic complications. Therefore, studying the endogenous regeneration of pancreatic β-cells may suggest strategies for alternative and long-lasting approaches for T1D management [ 3 ].…”

“…Endogenous β-cell regeneration is thought to occur either by whole islet neogenesis (WIN) via the differentiation of progenitor cells within the adult pancreas, or by β-cell replication (BCR) and the regeneration of new β-cells from pre-existing β-cells [ 3 , 4 ]. Using non-obese diabetic (NOD) or streptozotocin-injected C57/BL6 mice as a model for T1D, several groups have shown a possible role for transcription factors, growth factors, and regeneration genes in stimulating β-cell regeneration.…”

“…This could result in whole islet neogenesis (WIN) and subsequent insulin production and diabetes reversal. Some of these candidate factors include pancreatic and duodenal homeobox 1 (PDX-1), glucagon-like peptide-1 (GLP-1), islet neogenesis-associated protein (INGAP) and Regenerating protein 1 and 2 (Reg1 and Reg2) [ 3 , 5 – 9 ]. Recently, platelet-derived growth factor (PDGF) has also been shown to stimulate β-cell regeneration via activating cyclin D1 and inducing a G1 to S transition of the β-cell cycle [ 10 ].…”

Restrain of beta-cell destruction and stimulation of beta-cell regeneration in type 1 diabetes

“…2015.14.3.52. [35][36][37][38][39][40] Próby hamowania destrukcji oraz stymulacji odnowy komórek beta trzustki w cukrzycy typu l beta może być efektem proliferacji prekursorów (preexisting) komórek beta. Collombat i wsp.…”