Calcium/calmodulin-dependent serine protein kinase (CASK) is involved in the secretion of insulin vesicles in pancreatic β-cells. The current study revealed a new in vivo role of CASK in glucose homeostasis during the progression of type 2 diabetes mellitus (T2DM). A Cre-loxP system was used to specifically delete the Cask gene in mouse β-cells (βCASKKO), and glucose metabolism was evaluated in βCASKKO mice fed a normal chow diet (ND) or a high-fat diet (HFD). ND-fed mice exhibited impaired insulin secretion in response to glucose stimulation. Transmission electron microscopy showed significantly reduced numbers of insulin granules at or near the cell membrane in the islets of βCASKKO mice. By contrast, HFD-fed βCASKKO mice showed reduced blood glucose and a partial relief of hyperinsulinemia and insulin resistance when compared with HFD-fed wild-type mice. The IRS1/PI3K/AKT signaling pathway was upregulated in the adipose tissue of HFD-fed βCASKKO mice. These results indicated that knockout of the Cask gene in β-cells had a diverse effect on glucose homeostasis; it reduced insulin secretion in ND-fed mice but improved insulin sensitivity in HFD-fed mice. Therefore, CASK appears to function in insulin secretion and contributes to hyperinsulinemia and insulin resistance during the development of obesity-related T2DM.
X-box-binding protein 1 (XBP1) is a protein containing the basic leucine zipper structure. It belongs to the cAMP-response element binding protein (CREB)/activating transcription factor transcription factor family. As the main transcription factor, spliced XBP1 (XBP1s) participates in many physiological and pathological processes and plays an important role in embryonic development. Previous studies showed that XBP1-knockout mice died because of pancreatic exocrine function deficiency, indicating that XBP1 plays an important role in pancreatic development. However, the exact role of XBP1 in pancreatic development remains unclear. This study aimed to investigate the role of XBP1 in the pancreatic development of Xenopus laevis embryos. Whole-mount in situ hybridization and quantitative real-time PCR (qRT-PCR) results revealed that the expression levels of pancreatic progenitor marker genes pdx1, p48, ngn3, and sox9 were downregulated in XBP1s morpholino oligonucleotide (MO)-injected embryos. The expression levels of pancreatic exocrine and endocrine marker genes insulin and amylase were also downregulated. Through the overexpression of XBP1s, the phenotype and gene expressions were opposite to those in XBP1s MO-injected embryos. Luciferase and chromatin immunoprecipitation assays showed that XBP1s could bind to the XBP1-binding site in the foxa2 promoter. These results revealed that XBP1 is required in the pancreatic development of Xenopus laevis and might function by regulating foxa2.
Calcium/calmodulin-dependent serine protein
kinase (CASK) is involved in the secretion of insulin vesicles in pancreatic
β-cells. The present study revealed a new <i>in
vivo </i>role of CASK in glucose homeostasis during the progression of type 2 diabetes mellitus (T2DM). A
Cre-loxP system was used to specifically delete the <i>Cask </i>gene in mouse
β-cells (βCASKKO), and the glucose metabolism was evaluated in <a>βCASKKO</a> mice fed a normal chow diet (ND) or a high-fat
diet (HFD). ND-fed mice exhibited impaired insulin secretion in response to
glucose stimulation. Transmission electron microscopy showed significantly
reduced numbers of insulin granules at or near the cell membrane in the islets
of βCASKKO mice. By contrast, HFD-fed βCASKKO mice showed reduced blood glucose
and a partial relief of hyperinsulinemia and insulin resistance when compared
to HFD-fed wildtype mice. The IRS1/PI3K/AKT signaling pathway was upregulated
in the adipose tissue of HFD-βCASKKO mice. These results indicated that
knockout of the <i>Cask</i> gene in β cells had a diverse effect on glucose
homeostasis: reduced insulin secretion in ND-fed mice, but improves insulin
sensitivity in HFD-fed mice. Therefore, CASK appears to function in the insulin
secretion and contributes to hyperinsulinemia and insulin resistance during the
development of obesity-related T2DM.
The mechanism of the treatment of psoriasis-like mice with the Chinese herbal compound YinXie No.1 prepared by nano-suspension technology was investigated based on Janus kinase-signal transducers and activators of transcription (JAKs/STATs) pathway. The high-pressure homogenization technology was used in the preparation of the YinXie No.1 nano-suspensions. Then, 50 Kunming mice were equally classified into the negative control group (NC), the psoriasis model group (PsM) prepared with 5% imiquimod cream on the back, the Tripterygium glycosides-gavage group (TrG), the YinXie No.1gavage group (YX1), and the YinXie No.1 nano-suspension group (Nano-YX1). The pathological changes and the differential expressions of STAT3 and STAT5 were compared in each group after the treatment. The results showed that the particle size of nano-suspension powder was smaller and had strong stability compared with the active pharmaceutical ingredient (API). Compared with the NC group, psoriasis-like lesions were observed in the PsM group. Compared with the PsM group, the conditions of the erythema on skin lesions, the mRNA expression of STAT3 and STAT5, and protein expression of p-STAT3 and p-STAT5 in the TrG group, YX1 group, and Nano-YX1 group were notably decreased (P<0.05). Compared with the TrG group and YX1 group, the improvement effect of various indexes in the Nano-YX1 group was closer to that in the NC group, but there were differences between the NC group (P<0.05). Chinese herbal compound was helpful to regulate and control the JAKs/STATs pathway to improve the symptoms of psoriasis mice, and the preparation of Chinese herbal compound decoction by nano-suspension technology could improve the therapeutic effect.
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