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SGLT2 inhibitor canagliflozin alleviates vascular calcification through suppression of NLRP3 inflammasome
CONCLUSIONS: Our study for the first time demonstrates that CANA exerts a protective effect on vascular calcification at least partially via suppressing NLRP3 signaling pathway. Therefore, supplementation of CANA as well as inhibition of NLRP3 inflammasome presents a potential therapy for vascular calcification.PMID:37523743 | DOI:10.1093/cvr/cvad119
Source: Atherosclerosis - July 31, 2023 Category: Cardiology Authors: An Chen Zirong Lan Li Li Luting Xie Xiaoyu Liu Xiulin Yang Siyi Wang Qingchun Liang Qianqian Dong Liyun Feng Yining Li Yuanzhi Ye Mingwei Fu Lihe Lu Jianyun Yan Source Type: research

Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF/EPAC-Ca < sup > 2+ < /sup > -PPP3/calcineurin-TFEB axis
Autophagy. 2021 Aug 2:1-17. doi: 10.1080/15548627.2021.1956123. Online ahead of print.ABSTRACTMacroautophagy/autophagy is critical for the regulation of pancreatic β-cell mass and its deregulation has been implicated in the pathogenesis of type 2 diabetes (T2D). We have previously shown that treatment of pancreatic β-cells with the GLP1R (glucagon like peptide 1 receptor) agonist exendin-4 stimulates autophagic flux in a setting of chronic nutrient excess. The aim of this study was to identify the underlying pathways contributing to enhanced autophagic flux.Pancreatic β-cells (INS-1E),mouse and human islets were treated...
Source: Autophagy - August 2, 2021 Category: Cytology Authors: Francesco P Zummo Stanislaus I Krishnanda Merilin Georgiou Finbarr Pm O'Harte Vadivel Parthsarathy Kirsty S Cullen Minna Honkanen-Scott James Am Shaw Penny E Lovat Catherine Arden Source Type: research

TMEM16A channel upregulation in arterial smooth muscle cells produces vasoconstriction during diabetes.
Abstract The pathological involvement of anion channels in vascular dysfunction that occurs during type 2 diabetes (T2D) is unclear. Here, we tested the hypothesis that TMEM16A, a calcium (Ca2+)-activated chloride (Cl-) channel, contributes to modifications in arterial contractility during T2D. Our data indicate that T2D increased TMEM16A mRNA in arterial smooth muscle cells (myocytes) and total and surface TMEM16A protein in resistance-size arteries of mice. To examine vascular cell types in which TMEM16A expression is upregulated, we generated a tamoxifen-inducible, smooth muscle-specific TMEM16A knockout (TMEM1...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 15, 2021 Category: Physiology Authors: Leo MD, Peixoto-Neves D, Yin W, Raghavan S, Muralidharan P, Mata-Daboin A, Jaggar JH Tags: Am J Physiol Heart Circ Physiol Source Type: research

The TRPC6-AMPK Pathway is Involved in Insulin-Dependent Cytoskeleton Reorganization and Glucose Uptake in Cultured Rat Podocytes
Conclusion: These results suggest a potentially important new mechanism that regulates glucose transport in podocytes and that could be injurious during diabetes.Cell Physiol Biochem 2018;51:393 –410
Source: Cellular Physiology and Biochemistry - November 19, 2018 Category: Cytology Source Type: research

LncRNA uc.48+ is involved in the diabetic immune and inflammatory responses mediated by P2X7 receptor in RAW264.7 macrophages.
Abstract High glucose combined with high FFAs can contribute to the unfavorable development of type 2 diabetes mellitus (T2DM) and monocytes/macrophages are important in the occurrence and development of T2DM, which is regarded as a type of low‑grade inflammation. Although our previous study demonstrated that increased expression of P2X7 receptor (P2X7R) in peripheral blood monocytes may alter the innate immune system and that long non‑coding (lnc)RNA uc.48+ was involved in diabetic neuropathic pain, the involvement of uc.48+ mediated by the P2X7R in monocyte/macrophages during T2DM has not been reported. In t...
Source: International Journal of Molecular Medicine - May 9, 2018 Category: Molecular Biology Authors: Wu H, Wen F, Jiang M, Liu Q, Nie Y Tags: Int J Mol Med Source Type: research

Androgen signaling expands β-cell mass in male rats and β-cell androgen receptor is degraded under high-glucose conditions.
Abstract A deficient pancreatic β-cell mass increases the risk of type 2 diabetes mellitus. Here, we investigated the effects of testosterone on the development of pancreatic β-cell mass in male rats. The β-cell mass of male rats castrated at 6 weeks of age was reduced to ~30% of that of control rats at 16 weeks of age, and castration caused glucose intolerance. Loss of β-cell mass occurred due to decreases in islet density/pancreas and β-cell cluster size. Castration was negatively associated with the number of Ki67-positive β-cells and positively associated with the number of TUNEL-positive β-cells. These...
Source: Am J Physiol Endocri... - November 14, 2017 Category: Endocrinology Authors: Harada N, Yoda Y, Yotsumoto Y, Masuda T, Takahashi Y, Katsuki T, Kai K, Shiraki N, Inui H, Yamaji R Tags: Am J Physiol Endocrinol Metab Source Type: research

A Hypothalamic Leptin-Glutamate Interaction in the Regulation of Sympathetic Nerve Activity.
In conclusion, these studies provide evidence that within the hypothalamic nuclei, leptin-glutamate signaling regulates the sympathetic activation. This may contribute to the sympathoexcitation commonly observed in obesity-related T2D. PMID: 28845307 [PubMed - in process]
Source: Neural Plasticity - August 30, 2017 Category: Neurology Authors: Zheng H, Liu X, Li Y, Patel KP Tags: Neural Plast Source Type: research