Regeneration of pancreatic islets after partial pancreatectomy in mice does not involve the reactivation of neurogenin-3.
Understanding the factors and mechanisms involved in beta-cell regeneration will guide therapeutic efforts to augment beta-cell mass in patients with diabetes. Neurogenin-3 (Ngn3) is a bHLH transcription factor that responds to Notch signaling and whose expression marks endocrine progenitors. During fetal development, all endocrine cells are derived from Ngn3(+) precursors. Although expression of Ngn3 in the adult pancreas has not been reported, it has been suggested that islet regeneration in adult organisms recapitulates embryonic developmental pathways. Here, we investigated whether beta-cell regeneration in adult mice recapitulates the embryonic pathway involving Ngn3 activation. Despite full recovery of beta-cell mass after 50% partial pancreatectomy (Ppx) in BALB/c mice, no pancreatic Ngn3 immunoreactivity was detected, even when the beta-cell trophic glucagon-like peptide-1 receptor agonist exendin-4 was administered after the procedure. Even when we used the stable expression of enhanced green fluorescent protein (EGFP) in Ngn3(EGFP/+) mice to trace Ngn3 expression after Ppx, no pancreatic Ngn3 expression was detected. Although ectopic expression of Ngn3 can promote an endocrine transcriptional program in adult cells and may thus have therapeutic potential in the development of surrogate beta-cells, our studies indicate that a reactivation of endogenous Ngn3 expression is not required for adult beta-cell regeneration in vivo.
Lee
Catherine S
CS
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Clinical Research Building 611 B, Philadelphia, 19104, USA.
De León
Diva D
DD
Kaestner
Klaus H
KH
Stoffers
Doris A
DA
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D010180:Pancreatectomy; D012038:Regeneration / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C407737:Neurog3 protein, mouse