Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreaticβ-cell Dysfunction

Objective:While the reduction of transient receptor potential channel subfamily M member 5(TRPM5)has been reported in islet cells from type 2 diabetic(T2D)mouse models,its role in lipotoxicity-induced pancreaticβ-cell dysfunction remains unclear.This study aims to study its role.Methods:Pancreas slices were prepared from mice subjected to a high-fat-diet(HFD)at different time points,and TRPM5 expression in the pancreaticβcells was examined using immunofluorescence staining.Glucose-stimulated insulin secretion(GSIS)defects caused by lipotoxicity were mimicked by saturated fatty acid palmitate(Palm).Primary mouse islets and mouse insulinoma MIN6 cells were treated with Palm,and the TRPM5 expression was detected using qRT-PCR and Western blotting.Palm-induced GSIS defects were measured following siRNA-based Trpm5 knockdown.The detrimental effects of Palm on primary mouse islets were also assessed after overexpressing Trpm5 via an adenovirus-derived Trpm5(Ad-Trpm5).Results:HFD feeding decreased the mRNA levels and protein expression of TRPM5 in mouse pancreatic islets.Palm reduced TRPM5 protein expression in a time-and dose-dependent manner in MIN6 cells.Palm also inhibited TRPM5 expression in primary mouse islets.Knockdown of Trpm5 inhibited insulin secretion upon high glucose stimulation but had little effect on insulin biosynthesis.Overexpression of Trpm5 reversed Palm-induced GSIS defects and the production of functional maturation molecules unique toβcells.Conclusion:Our findings suggest that lipotoxicity inhibits TRPM5 expression in pancreaticβcells both in vivo and in vitro and,in turn,drivesβ-cell dysfunction.

MRI diagnosis of bone and seminal vesicle metastasis in prostate cancer

Objective:To study the value of MRI in the diagnosis of bone and seminal vesicle metastasis of prostate cancer, and to provide reference for clinical diagnosis.Methods: A total of 136 cases of prostate cancer treated in our hospital in December 2017 December 2015 were collected. MRI prostate and peripheral tissue, pelvic and spinal scan were performed before the puncture biopsy, and systematic biopsy of the prostate was performed at the end. The specificity, accuracy and sensitivity of MRI scan in the diagnosis of bone and seminal vesicle metastasis of prostate cancer were compared with the pathological diagnosis as gold standard. Results: The pathological diagnosis of 136 cases of prostate cancer occurred in 34 cases (25%), including 16 cases of seminal vesicle metastasis (10.3%), and 20 cases of bone metastases (14.7%). A total of 42 cases of metastasis (30.9%) were diagnosed by MRI, of which 20 cases (14.7%) were metastases of seminal vesicle and 22 cases of bone metastases (16.2%). The specificity of MRI for the diagnosis of prostate cancer seminal vesicle and bone metastases was 95.7%, the sensitivity was 76.2%, and the accuracy was 89.7%.Conclusion: Compared with pathological biopsy, MRI has high specificity and accuracy in diagnosing seminal vesicle metastasis and bone metastasis in patients with prostate cancer, but the sensitivity is deficient. It is worth promoting in clinic.