can alpha be converted into beta
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Abstract
Beta-cell deficit is the major pathological feature in type 1 and type 2 diabetes patients, and plays a key role in disease progression. In principle, beta-cell regeneration can occur by replication of pre-existing beta-cells, or by beta-cell neogenesis from stem/progenitors. Unfortunately, beta-cell replication is limited by the almost complete absence of beta-cells in patients with type 1 diabetes, and the increasing recognition that the beta-cell replicative capacity declines severely with age. Therefore, beta-cell neogenesis has received increasing interest. Many different cell types within the pancreas have been suggested as potential beta-cell stem/progenitor cells, but the data have been conflicting. In some cases, this may be due to different regeneration models. On the other hand, different results have been obtained with similar regeneration models, leading to confusion about the nature and existence of beta-cell neogenesis in adult animals. Here, we review the major candidates for adult regeneration pathways, and focus on the recent discovery that alpha-cells can function as a novel beta-cell progenitor. Of note, this is a pathway that appears to be unique to beta-cell neogenesis in the adult, as the embryonic pathway of beta-cell neogenesis does not proceed through a glucagon-positive intermediate. We conclude that beta-cell neogenesis from alpha-cells is a new pathway of potential therapeutic significance, making it of high importance to elucidate the molecular events in alpha- to beta-cell conversion.
Keywords: stem cell, duct, pancreatic duct ligation, beta-cell, alpha-cell, conversion, insulin, glucagon, genetic lineage tracing, proliferation
Abbreviations: BrdU - bromodeoxyuridine or 5-bromo-2-deoxyuridine (analogue of thymidine; used in the detection of proliferating cells in living tissues); Cre recombinase - type I topoisomerase (catalyzes site-specific recombination of DNA between loxP sites); EGF - epidermal growth factor; IGF-1- insulin-like growth factor 1; IL - interleukin; MafA - v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (transcription factor necessary for beta-cell maturation); MafB - v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (transcription factor important for alpha- and beta-cell development and mature alpha-cell function); mRNA - messenger ribonucleic acid; NF-kappaB - nuclear factor kappa-light-chain-enhancer of activated B-cells; Nkx6.1 - homeobox protein required for β-cell development; Pax4 - paired box gene 4 (transcription factor involved in fetal and pancreas development); PDL - partial duct ligation; Pdx1 - pancreatic and duodenal homeobox 1 (transcription factor necessary for pancreas development); T1D - type 1 diabetes; T2D - type 2 diabetes; TGF-alpha - transforming growth factor alpha
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Abstract
Beta-cell deficit is the major pathological feature in type 1 and type 2 diabetes patients, and plays a key role in disease progression. In principle, beta-cell regeneration can occur by replication of pre-existing beta-cells, or by beta-cell neogenesis from stem/progenitors. Unfortunately, beta-cell replication is limited by the almost complete absence of beta-cells in patients with type 1 diabetes, and the increasing recognition that the beta-cell replicative capacity declines severely with age. Therefore, beta-cell neogenesis has received increasing interest. Many different cell types within the pancreas have been suggested as potential beta-cell stem/progenitor cells, but the data have been conflicting. In some cases, this may be due to different regeneration models. On the other hand, different results have been obtained with similar regeneration models, leading to confusion about the nature and existence of beta-cell neogenesis in adult animals. Here, we review the major candidates for adult regeneration pathways, and focus on the recent discovery that alpha-cells can function as a novel beta-cell progenitor. Of note, this is a pathway that appears to be unique to beta-cell neogenesis in the adult, as the embryonic pathway of beta-cell neogenesis does not proceed through a glucagon-positive intermediate. We conclude that beta-cell neogenesis from alpha-cells is a new pathway of potential therapeutic significance, making it of high importance to elucidate the molecular events in alpha- to beta-cell conversion.
Keywords: stem cell, duct, pancreatic duct ligation, beta-cell, alpha-cell, conversion, insulin, glucagon, genetic lineage tracing, proliferation
Abbreviations: BrdU - bromodeoxyuridine or 5-bromo-2-deoxyuridine (analogue of thymidine; used in the detection of proliferating cells in living tissues); Cre recombinase - type I topoisomerase (catalyzes site-specific recombination of DNA between loxP sites); EGF - epidermal growth factor; IGF-1- insulin-like growth factor 1; IL - interleukin; MafA - v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (transcription factor necessary for beta-cell maturation); MafB - v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (transcription factor important for alpha- and beta-cell development and mature alpha-cell function); mRNA - messenger ribonucleic acid; NF-kappaB - nuclear factor kappa-light-chain-enhancer of activated B-cells; Nkx6.1 - homeobox protein required for β-cell development; Pax4 - paired box gene 4 (transcription factor involved in fetal and pancreas development); PDL - partial duct ligation; Pdx1 - pancreatic and duodenal homeobox 1 (transcription factor necessary for pancreas development); T1D - type 1 diabetes; T2D - type 2 diabetes; TGF-alpha - transforming growth factor alpha
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