Differentiation, reduction, and proliferation of pancreatic β-cells and their regulatory factors.

IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM
Diabetology International Pub Date : 2024-11-28 eCollection Date: 2025-01-01 DOI:10.1007/s13340-024-00774-x
Akari Inada
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Abstract

The prevalence of diabetes has increased rapidly in recent years, and many types of therapeutic agents have been developed. However, the main purpose of these drugs is to lower blood glucose levels, and they are not fundamental solutions. In contrast, our research has been aimed at stimulating and inducing β-cell proliferation in vivo and replenishing β-cells. We demonstrated that pancreatic ductal cells are a source of β-cells both after birth and during regeneration after partial duct ligation: cell lineage tracing showed that 39% of growing islets and 50% of adult islets during tissue regeneration contained β-cells differentiated from duct cells. We also examined the factors contributing to β-cell depletion. Insulin and cyclin A genes are tightly regulated by transcriptional activators and repressors, and we found that imbalanced and excessive levels of repressors result in a drastic reduction of insulin and β-cell numbers, leading to severe diabetes. Thus, we searched for factors that induce β-cell proliferation in vivo. In our transgenic (Tg) mice, there was a sex difference in the progression of diabetes and sex steroid hormones were shown to contribute to this. Surprisingly, in diabetic male Tg mice, modulation of sex steroid hormones under certain conditions resulted in a marked increase of β-cells. We identified Greb1 as a factor inducing β-cell proliferation in response to a rapid elevation of E2 levels. This series of studies has demonstrated that islet cells exhibit plasticity and indicates that changes of islet cell mass and function are dynamic and recoverable.

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来源期刊
Diabetology International
Diabetology International ENDOCRINOLOGY & METABOLISM-
CiteScore
3.90
自引率
4.50%
发文量
42
期刊介绍: Diabetology International, the official journal of the Japan Diabetes Society, publishes original research articles about experimental research and clinical studies in diabetes and related areas. The journal also presents editorials, reviews, commentaries, reports of expert committees, and case reports on any aspect of diabetes. Diabetology International welcomes submissions from researchers, clinicians, and health professionals throughout the world who are interested in research, treatment, and care of patients with diabetes. All manuscripts are peer-reviewed to assure that high-quality information in the field of diabetes is made available to readers. Manuscripts are reviewed with due respect for the author''s confidentiality. At the same time, reviewers also have rights to confidentiality, which are respected by the editors. The journal follows a single-blind review procedure, where the reviewers are aware of the names and affiliations of the authors, but the reviewer reports provided to authors are anonymous. Single-blind peer review is the traditional model of peer review that many reviewers are comfortable with, and it facilitates a dispassionate critique of a manuscript.
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