Conversion of pancreatic α cells into insulin-producing cells modulated by β-cell insufficiency and supplemental insulin administration

• Published in: Biochemical and biophysical research communications Vol. 521; no. 1; pp. 178 - 183
• Main Authors: Katahira, Takehiro, Miyatsuka, Takeshi, Miura, Masaki, Suzuki, Luka, Himuro, Miwa, Nishida, Yuya, Satoh, Hiroaki, Watada, Hirotaka
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020
• Subjects: Bihormonal cell; Diabetes; Glucagon; Insulin; α-To-β conversion; Bihormonal cell; Diabetes; Glucagon; α-To-β conversion; Insulin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.10.100

The emergence of bihormonal (BH) cells expressing insulin and glucagon has been reported under diabetic conditions in humans and mice. Whereas lineage tracing studies demonstrated that glucagon-producing α cells can be reprogrammed into BH cells, the underlying dynamics of the conversion process remain poorly understood. In the present study, we investigated the identities of pancreatic endocrine cells by genetic lineage tracing under diabetic conditions. When β-cell ablation was induced by alloxan (ALX), a time-dependent increase in BH cells was subsequently observed. Lineage tracing experiments demonstrated that BH cells originate from α cells, but not from β cells, in ALX-induced diabetic mice. Notably, supplemental insulin administration into diabetic mice resulted in a significant increase in α-cell-derived insulin-producing cells that did not express glucagon. Furthermore, lineage tracing in Ins2Akita diabetic mice demonstrated a significant induction of α-to-β conversion. Thus, adult α cells have plasticity, which enables them to be reprogrammed into insulin-producing cells under diabetic conditions, and this can be modulated by supplemental insulin administration. •Alloxan-induced β-cell ablation increased bihormonal cells expressing insulin and glucagon.•Bihormonal cells expressing insulin and glucagon originate from α cells, but not from β cell.•Supplemental insulin administration increases α-cell-derived insulin-producing cells with the loss of glucagon expression.