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Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle
Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anteri...
Source: AJP: Endocrinology and Metabolism - October 1, 2017 Category: Endocrinology Authors: Ruby, M. A., Riedl, I., Massart, J., Ahlin, M., Zierath, J. R. Tags: Research Article Source Type: research

Exogenous H2S regulates endoplasmic reticulum-mitochondria cross-talk to inhibit apoptotic pathways in STZ-induced type I diabetes
This study investigated cardiac function, ultrastructural changes in the ER and mitochondria, apoptotic rate using TUNEL, and the expression of ER stress-associated proteins and mitochondrial apoptotic proteins in cardiac tissues in STZ-induced type I diabetic rats treated with or without NaHS (donor of H2S). Mitochondria of cardiac tissues were isolated, and MPTP opening and cytochrome c (cyt C) and Mfn-2 expression were also detected. Our data showed that hyperglycemia decreased the cardiac function by ultrasound cardiogram, and the administration of exogenous H2S ameliorated these changes. We demonstrated that the expre...
Source: AJP: Endocrinology and Metabolism - March 1, 2017 Category: Endocrinology Authors: Yang, F., Yu, X., Li, T., Wu, J., Zhao, Y., Liu, J., Sun, A., Dong, S., Wu, J., Zhong, X., Xu, C., Lu, F., Zhang, W. Tags: Research Article Source Type: research

Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of L-DOPA
This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is...
Source: AJP: Endocrinology and Metabolism - December 31, 2016 Category: Endocrinology Authors: Jiang, X., Zhang, Y., Yang, Y., Yang, J., Asico, L. D., Chen, W., Felder, R. A., Armando, I., Jose, P. A., Yang, Z. Tags: Research Article Source Type: research

Involvement of a proapoptotic gene (BBC3) in islet injury mediated by cold preservation and rewarming
In this study, we examined mechanisms of pancreatic cold preservation and rewarming-induced injury by interrogating the proapoptotic gene BBC3/Bbc3, also known as Puma (p53 upregulated modulator of apoptosis), using three experimental models: 1) bioluminescence imaging of isolated luciferase-transgenic ("Firefly") Lewis rat islets, 2) cold preservation of en bloc-harvested pancreata from Bbc3-knockout (KO) mice, and 3) cold preservation and rewarming of human pancreata and isolated islets. Cold preservation-mediated islet injury occurred during rewarming in "Firefly" islets. Silencing Bbc3 by transfecting Bbc3 siRNA into i...
Source: AJP: Endocrinology and Metabolism - June 13, 2016 Category: Endocrinology Authors: Omori, K., Kobayashi, E., Komatsu, H., Rawson, J., Agrawal, G., Parimi, M., Oancea, A. R., Valiente, L., Ferreri, K., Al-Abdullah, I. H., Kandeel, F., Takahashi, M., Mullen, Y. Tags: Call for Papers Source Type: research

Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1 receptor-dependent manner
In conclusion, exenatide significantly improves coronary endothelial function in patients with newly diagnosed type 2 diabetes. The effect may be mediated through activation of AMPK/PI3K-Akt/eNOS pathway via a GLP-1R/cAMP-dependent mechanism.
Source: AJP: Endocrinology and Metabolism - May 31, 2016 Category: Endocrinology Authors: Wei, R., Ma, S., Wang, C., Ke, J., Yang, J., Li, W., Liu, Y., Hou, W., Feng, X., Wang, G., Hong, T. Tags: Articles Source Type: research

Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice
Impairment of skeletal muscle function has been associated with changes in ovarian hormones, especially estradiol. To elucidate mechanisms of estradiol on skeletal muscle strength, the hormone's effects on phosphorylation of the myosin regulatory light chain (pRLC) and muscle contractility were investigated, hypothesizing an estradiol-specific beneficial impact. In a skeletal muscle cell line, C2C12, pRLC was increased by 17β-estradiol (E2) in a concentration-dependent manner. In skeletal muscles of C57BL/6 mice that were E2 deficient via ovariectomy (OVX), pRLC was lower than that from ovary-intact, sham-operated mic...
Source: AJP: Endocrinology and Metabolism - May 1, 2016 Category: Endocrinology Authors: Lai, S., Collins, B. C., Colson, B. A., Kararigas, G., Lowe, D. A. Tags: Call for Papers Source Type: research

Zinc transporter Slc39a14 regulates inflammatory signaling associated with hypertrophic adiposity
Zinc is a signaling molecule in numerous metabolic pathways, the coordination of which occurs through activity of zinc transporters. The expression of zinc transporter Zip14 (Slc39a14), a zinc importer of the solute carrier 39 family, is stimulated under proinflammatory conditions. Adipose tissue upregulates Zip14 during lipopolysaccharide-induced endotoxemia. A null mutation of Zip14 (KO) revealed that phenotypic changes in adipose include increased cytokine production, increased plasma leptin, hypertrophied adipocytes, and dampened insulin signaling. Adipose tissue from KO mice had increased levels of preadipocyte marker...
Source: AJP: Endocrinology and Metabolism - February 15, 2016 Category: Endocrinology Authors: Troche, C., Beker Aydemir, T., Cousins, R. J. Tags: Call for Papers Source Type: research

Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway
Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (Na...
Source: AJP: Endocrinology and Metabolism - December 1, 2015 Category: Endocrinology Authors: Sun, L., Zhang, S., Yu, C., Pan, Z., Liu, Y., Zhao, J., Wang, X., Yun, F., Zhao, H., Yan, S., Yuan, Y., Wang, D., Ding, X., Liu, G., Li, W., Zhao, X., Liu, Z., Li, Y. Tags: Articles Source Type: research

(Pro)renin receptor regulates autophagy and apoptosis in podocytes exposed to high glucose
High glucose reduces autophagy and enhances apoptosis of podocytes. Previously, we reported that high glucose induced podocyte injury through upregulation of the (pro)renin receptor (PRR). We hypothesized that increasing PRR reduces autophagy and increases apoptosis of mouse podocytes exposed to high glucose via activation of the PI3K/Akt/mTOR signaling pathway. Mouse podocytes were cultured in normal (5 mmol/l) or high (25 mmol/l) d-glucose for 48 h. High glucose significantly increased mRNA and protein levels of PRR, phosphorylation of PI3K/Akt/mTOR, and p62. In contrast, high glucose decreased activation of UNC-51-like ...
Source: AJP: Endocrinology and Metabolism - August 1, 2015 Category: Endocrinology Authors: Li, C., Siragy, H. M. Tags: Articles Source Type: research

New CETP inhibitor K-312 reduces PCSK9 expression: a potential effect on LDL cholesterol metabolism
Despite significant reduction of cardiovascular events by statin treatment, substantial residual risk persists, driving emerging needs for the development of new therapies. We identified a novel cholesteryl ester transfer protein (CETP) inhibitor, K-312, that raises HDL and lowers LDL cholesterol levels in animals. K-312 also suppresses hepatocyte expression of proprotein convertase subtilisin/kexin 9 (PCSK9), a molecule that increases LDL cholesterol. We explored the underlying mechanism for the reduction of PCSK9 expression by K-312. K-312 inhibited in vitro human plasma CETP activity (IC50; 0.06 μM). Administration o...
Source: AJP: Endocrinology and Metabolism - July 15, 2015 Category: Endocrinology Authors: Miyosawa, K., Watanabe, Y., Murakami, K., Murakami, T., Shibata, H., Iwashita, M., Yamazaki, H., Yamazaki, K., Ohgiya, T., Shibuya, K., Mizuno, K., Tanabe, S., Singh, S. A., Aikawa, M. Tags: Articles Source Type: research

Dysregulation of low-density lipoprotein receptor contributes to podocyte injuries in diabetic nephropathy
This study investigated the effects of high glucose on lipid accumulation in podocytes and explored its underlying mechanisms. Male db/m and db/db mice were fed a normal chow diet for 8 wk. Immortalised mouse podocytes were treated with or without high glucose for 24 h. The changes to the morphology and ultramicrostructures of the kidneys in mice were examined using pathological staining and electron microscopy. Intracellular lipid accumulation was evaluated by Oil Red O staining and a free cholesterol quantitative assay. The expressions of the molecules involved in low-density lipoprotein receptor (LDLr) pathway and podoc...
Source: AJP: Endocrinology and Metabolism - June 15, 2015 Category: Endocrinology Authors: Zhang, Y., Ma, K. L., Liu, J., Wu, Y., Hu, Z. B., Liu, L., Liu, B. C. Tags: Articles Source Type: research

Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-{alpha}
Progesterone exerts beneficial effects on the human cardiovascular system by inducing rapid increases in nitric oxide (NO) production in vascular endothelial cells, but the receptors mediating these nongenomic progesterone actions remain unclear. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that progesterone binds to plasma membranes of HUVECs with the characteristics of membrane progesterone receptors (mPRs). The selective mPR agonist Org OD 02-0 had high binding affinity for the progesterone receptor on HUVEC membranes, whereas nuclear PR (nPR) agonists R5020 and medroxyprogesterone acetate d...
Source: AJP: Endocrinology and Metabolism - May 15, 2015 Category: Endocrinology Authors: Pang, Y., Dong, J., Thomas, P. Tags: Articles Source Type: research

Removal of Rev-erb{alpha} inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells
This study focused on Ptgs2, which is essential for decidualization, as a putative clock-controlled gene, and aimed to reveal the functions of clock genes in relation to Ptgs2 during decidualization. We compared the transcript levels of clock genes in the rat uterus on days 4.5 (D4.5) and 6.5 of pregnancy. The transcript levels of clock genes (Per2, Bmal1, Rorα, and Rev-erbα) had decreased at implantation sites on day 6.5 (D6.5e) compared with those on D4.5, whereas Ptgs2 transcripts had increased on D6.5e. Similar observations of Rev-erbα and Ptgs2 were also obtained in the endometrium on D6.5e by immuno...
Source: AJP: Endocrinology and Metabolism - April 15, 2015 Category: Endocrinology Authors: Isayama, K., Zhao, L., Chen, H., Yamauchi, N., Shigeyoshi, Y., Hashimoto, S., Hattori, M.-a. Tags: Articles Source Type: research

Inhibition of PKR impairs angiogenesis through a VEGF pathway
Peripheral artery disease (PAD) is a common clinical problem, and its pathophysiological mechanisms are incompletely understood. Double-stranded RNA-activated protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. Although PKR has been reported in antivirus and the immune system, the role of PKR in vascular function, especially in angiogenesis, is still unclear. PKR–/– mice were used in our experiments. Blood flow recovery was significantly delayed in PKR–/– vs. WT mice (Laser Doppler detection, n = 9, P < 0.01), accompanied by 34% reduced CD31-positive stain in ischemi...
Source: AJP: Endocrinology and Metabolism - March 15, 2015 Category: Endocrinology Authors: Zhu, Z., Zhong, H., Zhou, Q., Hu, X., Chen, D., Wang, J., Wu, J., Cai, J., Zhou, S., Chen, A. F. Tags: Articles Source Type: research

The active form of vitamin D, calcitriol, induces a complex dual upregulation of endothelin and nitric oxide in cultured endothelial cells
Despite the presence of vitamin D receptor (VDR) in endothelial cells, the effect of vitamin D on endothelial function is unknown. An unbalanced production of vasoactive endothelial factors such as nitric oxide (NO) or endothelin-1 (ET-1) results in endothelial dysfunction, which can alter the normal cardiovascular function. Present experiments were devoted to assess the effect of active vitamin D (calcitriol) on the synthesis of endothelial vasoactive factors. The results were that, in cells, calcitriol increased ET-1 and NO productions, which were measured by ELISA and fluorimetric assay, respectively. Calcitriol also in...
Source: AJP: Endocrinology and Metabolism - December 15, 2014 Category: Endocrinology Authors: Martinez-Miguel, P., Valdivielso, J. M., Medrano-Andres, D., Roman-Garcia, P., Cano-Penalver, J. L., Rodriguez-Puyol, M., Rodriguez-Puyol, D., Lopez-Ongil, S. Tags: Articles Source Type: research

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