renal-subcapsular-transplantation-2-deoxyguanosine-treated-murine

Renal Subcapsular Transplantation of 2'-Deoxyguanosine-Treated Murine Embryonic Thymus in Nude Mice

The thymus is an important central immune organ, which plays an essential role in the development and differentiation of T cells. Thymus transplantation ...

jinan university

Joint institute of Metabolic Medicine Between Jinan University and University of Hong Kong

Baseline β-cell mass is established during the early postnatal period when β-cells expand. In this study, we show that heterozygous ablation of  decreases baseline β-cell mass and subsequently impairs glucose tolerance. When exposed to a high-fat diet or on an  background, glucose intolerance was more severe in  mice compared with  mice, although no further decrease in the β-cell mass was detected. In islets of early postnatal  mice, the cell cycle was prolonged in β-cells due to downregulation of the cell cycle gene  Although Insm1 had a low affinity for the  promoter compared with other binding sites, binding affinity was strongly dependent on Insm1 levels. We observed dramatically decreased binding of Insm1 to the  promoter after downregulation of  expression. Furthermore, downregulation of  resulted in a prolonged cell cycle, and overexpression of Ccnd1 rescued cell cycle abnormalities observed in Insm1-deficient β-cells. We conclude that decreases in Insm1 interfere with β-cell specification during the early postnatal period and impair glucose homeostasis during metabolic stress in adults. Insm1 levels are therefore a factor that can influence the development of diabetes.

Haploinsufficiency of Insm1 Impairs Postnatal Baseline β-Cell Mass.

Obesity is caused by energy imbalance and accompanied by adipocyte hypertrophy and hyperplasia. Therefore, both enhancement of adipocyte energy expenditure and inhibition of adipogenesis are viable ways to combat obesity. Using the Ucp1-2A-luciferase reporter animal model previously reported by us as a screening platform, a chemical compound Linifanib was identified as a potent inducer of UCP1 expression in primary inguinal adipocytes in vitro and in vivo. Signal pathway analyses showed that Linifanib promoted adipocyte browning by attenuating STAT3 phosphorylation. The effects of Linifanib on adipocyte browning were blocked by the compound, SD19, which activates the STAT3 signaling cascade. Linifanib also inhibited adipocyte differentiation, by blocking mitotic clonal expansion, which could be rescued by STAT3 activator. Taken together, our results indicate that Linifanib might serve as a potential drug for the treatment of obesity.

Linifanib exerts dual anti-obesity effect by regulating adipocyte browning and formation.

Studying patients with rare Mendelian diabetes has uncovered molecular mechanisms regulating β-cell pathophysiology. Previous studies have shown that Class IIa histone deacetylases (HDAC4, 5, 7, and 9) modulate mammalian pancreatic endocrine cell function and glucose homeostasis.

Article	Year
Haploinsufficiency of Insm1 Impairs Postnatal Baseline β-Cell Mass. Diabetes\| PubMed ID: 30257979	2018
Linifanib exerts dual anti-obesity effect by regulating adipocyte browning and formation. Life sciences\| PubMed ID: 30708100	2019
HDAC4 mutations cause diabetes and induce β-cell FoxO1 nuclear exclusion. Molecular genetics & genomic medicine\| PubMed ID: 30968599	2019

Shiqi Jia

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