RESUMEN
Semaglutide is a well-designed drug with a special coating that allows for oral administration to patients with type 2 diabetes mellitus. However, patients taking oral semaglutide complain of its bitter taste. We therefore considered suggesting that patients take oral semaglutide with hot water. When the hot water temperature was increased to above 46.0°C but below 52.0°C, no bitter taste was perceived, with the daily mean interstitial glucose level remaining at the target range. Taking oral semaglutide with hot water helps reduce its bitter taste.
Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Calor , Humanos , Péptidos Similares al Glucagón/administración & dosificación , Administración Oral , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Calor/efectos adversos , Agua , Hipoglucemiantes/administración & dosificación , Gusto/efectos de los fármacosRESUMEN
AIMS: Sodium load increases endogenous glucagon-like peptide-1 (GLP-1) levels in humans. Therefore, patients with an increased amount of dietary sodium intake are supposed to have higher endogenous GLP-1 levels compared to those with less dietary sodium intake. Therefore, it can be hypothesized that patients with type 2 diabetes mellitus (T2DM) with more dietary sodium intake show better dipeptidyl peptidase-4 inhibitor (DPP-4i) effect on glycemic control because of the expected higher GLP-1 level. Thus, we performed a single-center cohort study to explore this idea. METHODS: Medical records of patients with T2DM prescribed DPP-4i in the last 11 years were investigated. Dietary sodium intake was measured before the DPP-4i prescription with Tanaka's formula using casual spot urine samples. The effect of DPP-4i on glycemic control was estimated by the subtraction of glycated hemoglobin (HbA1c) before DPP-4i initiation from HbA1c 1 year after DPP-4i administration. We analyzed 50 patients. RESULTS: DPP-4i improved HbA1c by -0.41% ± 0.66%. The effect of DPP-4i on glycemic control was significantly negatively correlated with the dietary sodium intake (r = -0.400). Thus, the more dietary sodium intake, the better the glycemic control by DPP-4i. CONCLUSIONS: Thus, patients can expect better plasma glucose control by DPP-4is if patients are taking increased dietary sodium intake.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Sodio en la Dieta , Humanos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Estudios de Cohortes , Hipoglucemiantes , Péptido 1 Similar al Glucagón , Dipeptidil-Peptidasas y Tripeptidil-PeptidasasRESUMEN
BACKGROUND AND AIMS: Triiodothyronine reduces sodium glucose cotransporter 2 expression in the kidney and increased glucose excretion in urine of alloxan-induced diabetic rats. Free thyroxine is also negatively associated with islet beta-cell function in euthyroid subjects. However, the influence of sodium glucose cotransporter 2 inhibitor on thyroid function in patients with type 2 diabetes mellitus has not been established. METHODS: We investigated thyroid function in patients with type 2 diabetes mellitus in the presence or absence of sodium glucose cotransporter 2 inhibitor in a multicenter retrospective study conducted between 2019 and 2021. All participants visited the hospital monthly for type 2 diabetes mellitus treatment and plasma glucose and glycated hemoglobin level measurements. Furthermore, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels were measured annually. RESULTS: Free triiodothyronine level and the free triiodothyronine:free thyroxine ratio in the group treated with sodium glucose cotransporter 2 inhibitor were significantly higher than the levels in the group not treated with sodium glucose cotransporter 2 inhibitor. Free triiodothyronine levels in the group treated with sodium glucose cotransporter 2 inhibitor were significantly higher than the levels in the group not treated with sodium glucose cotransporter 2 inhibitor (p = 0.040). Free thyroxine levels in the group treated with sodium glucose cotransporter 2 inhibitor were significantly lower than the levels in the group not treated with sodium glucose cotransporter 2 inhibitor (p = 0.002). Thyroid-stimulating hormone levels did not differ significantly between the two groups. CONCLUSIONS: Our findings show that sodium glucose cotransporter 2 inhibitor affects free triiodothyronine levels free thyroxine levels, and the free triiodothyronine:free thyroxine ratio.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Estudios Retrospectivos , Tirotropina , Tiroxina , Triyodotironina , HumanosRESUMEN
BACKGROUND: Previously, AF-956, which contains S356 of FAM83G and an N-terminal antenna peptide for entry into colon cancer cells, is markedly antiproliferative compared to a control peptide (AF-859), which lacks the N-terminal antenna peptide, by inducing apoptosis via the inhibition of HSP27 phosphorylation at residues S15 and S82. OBJECTIVE: Because FAM83G-derived peptides are promising lead compounds for colon cancer treatment, we reanalyzed the effect of AG-066, which contains S356 of FAM83G and an N-terminal antenna peptide for entry into the liver cancer cells. METHODS: HepG2 liver cancer cells were incubated with either AF-859 or AG-066 at a concentration of 54 µM at 37 °C for 24, 48, and 72 h. The effects of AF-859 and AG-066 on the cultured HepG2 cells were estimated using an inverted light microscope. Furthermore, the DNA ladder method and the dead cell assay were performed by applying Live/Dead Cell Staining Kit II. Erk phosphorylation was estimated by western blotting. RESULTS: Treatment with AG-066 markedly reduced HepG2 viable cell counts compared to the AF- 859-treated HepG2 cells, as evident from the significantly increased number of dead cells in the culture medium. Additionally, AG-066 treatment increased cellular DNA laddering. We found no difference in Erk phosphorylation status between the AG-066- and AF-859-treated groups. CONCLUSION: This study illustrated that the peptide with a structure based on FAM83G functions as a spontaneous apoptosis inducer for liver cancer cells. Hence, it is a promising lead compound for the treatment of liver cancer.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias del Colon , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Apoptosis , Células Hep G2 , Péptidos/farmacología , Proliferación CelularRESUMEN
Resolvins are pro-resolving lipid mediators with highly potent anti-inflammatory effects. Because of their polyunsaturated structures, however, they are unstable to oxygen as a drug prototype. To address this issue, we designed and synthesized CP-RvE3 as oxidatively stable congeners of RvE3 by replacing the cis-olefin with a cis-cyclopropane to avoid the unstable bisallylic structure. Although the oxidative stabilities of CP-RvE3 were not improved, ß-CP-RvE3 was 3.7 times more metabolically stable than RvE3. Thus, we identified ß-CP-RvE3 as a metabolically stable equivalent.
Asunto(s)
Ciclopropanos , Ácidos Grasos Insaturados , Ciclopropanos/farmacología , Ácidos Docosahexaenoicos/química , Ácidos Grasos Insaturados/químicaRESUMEN
Thyroid hormones are critical for the development of opsins involved in color vision. Hypothyroid mice show delayed M-opsin development and expanded distribution of S-opsin on the retina. However, the effects of maternal hypothyroidism on opsin development remain unknown. This study investigates the effects of congenital central hypothyroidism and maternal hypothyroidism on opsin development in thyrotropin-releasing hormone knockout (TRH-/-) mice. We examined the mRNA expression and protein distribution of S/M-opsin on postnatal days (P)12 and 17, as well as mRNA expression of type 2 and 3 iodothyronine deiodinase (DIO2 and DIO3, respectively) in the retina and type 1 iodothyronine deiodinase (DIO1) in the liver at P12 in TRH+/- mice born to TRH+/- or TRH-/- dams, and conducted S/M-opsin analysis in TRH+/+ or TRH-/- mice born to TRH+/- dams at P12, P17, and P30. M-opsin expression was lower in TRH+/- mice born to TRH-/- dams than in those born to TRH+/- dams, whereas S-opsin expression did not significantly differ between them. DIO1, DIO2, and DIO3 mRNA expression levels were not significantly different between the two groups; therefore, thyroid function in peripheral tissues in the pups was similar. S/M-opsin expression did not significantly differ between the TRH+/+ and TRH-/- mice born to TRH+/- dams on any postnatal day. These results demonstrate that maternal hypothyroidism causes M-opsin developmental delay during the early developmental stages of neonatal mice, and TRH-/- mice, a model of congenital central hypothyroidism, born to a euthyroid dam do not have delayed opsin development.
Asunto(s)
Hipotiroidismo Congénito , Yoduro Peroxidasa , Animales , Hipotiroidismo Congénito/genética , Hipotiroidismo Congénito/metabolismo , Yoduro Peroxidasa/genética , Yoduro Peroxidasa/metabolismo , Ratones , Opsinas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Tirotropina/metabolismo , Hormona Liberadora de Tirotropina/metabolismoRESUMEN
Obesity-associated type 2 diabetes mellitus is associated with the development of insulin resistance. Among several metabolites, resolvins that are metabolites of eicosapentaenoic acid have been shown to exert insulin-sensitizing effects; however, the role of resolvin E3 (RvE3) in glucose metabolism has not been studied. In this study, the effect of RvE3 on glucose metabolism in mice with high-fat diet-induced obesity and 3T3L1 adipocytes was studied. C57BL/6 mice fed a high-fat diet were administered RvE3, for which insulin tolerance, oral glucose tolerance tests, and the homeostasis model assessment of insulin resistance, were performed. RvE3 treatment significantly improved insulin sensitivity and glucose tolerance and regulated protein kinase B (Akt) phosphorylation in the adipose tissue. Moreover, RvE3 treatment enhanced the insulin-stimulated glucose transporter 4 (Glut4) translocation, glucose uptake, phosphatidylinositol-3-kinase (PI3K) activity, and Akt phosphorylation in 3T3L1 adipocytes, whereas a PI3K inhibitor inhibited the enhanced insulin-stimulated glucose uptake induced by RvE3. These findings indicate that RvE3 likely improves insulin sensitivity, resulting in the upregulation of glucose uptake in adipocytes by activating the PI3K/Akt signaling pathways. Collectively, the findings of this study show that RvE3 may play a role in glucose homeostasis and could be used as a potential therapeutic target for developing treatments for obesity-associated diabetes.
Asunto(s)
Adipocitos/efectos de los fármacos , Ácidos Grasos Insaturados/farmacología , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Células 3T3-L1 , Adipocitos/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Transportador de Glucosa de Tipo 4/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
Exocyst complex component 3-like 1 (EXOC3L1), which regulates insulin secretion, is ubiquitously present in heart, lung, liver, spleen, kidney, muscle, cerebellum, pituitary, adrenal grand, and pancreatic islets. Its deduced amino acid sequence has 31% identity and 53% similarity with Sec6, so they are considered isoforms. Since Sec6 suppresses apoptosis via HSP27, we investigated the involvement of EXOC3L1 expression in apoptosis. We found that overexpressed EXOC3L1 in Chinese hamster ovary cells significantly reduced cultured cell numbers. It also significantly increased apoptotic DNA ladder, caspase 3 activity, and cleavage of caspase 3 compared with the control. Thus, although Sec6 reduces apoptosis by increasing HSP27 phosphorylation, overexpressed EXOC3L1 alone can spontaneously induce apoptosis without apoptotic stimulators or inducers.
Asunto(s)
Apoptosis , Insulina/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animales , Células CHO/metabolismo , Caspasa 3/metabolismo , Cricetulus , Fragmentación del ADN , Electroporación , Proteínas de Choque Térmico HSP27/metabolismo , Humanos , Ratones , Fosforilación , Isoformas de Proteínas , Ratas , Especificidad por Sustrato , Distribución TisularRESUMEN
Overexpressed TBC1D8B, a GTPase-activating protein, significantly reduced cultured HCT116 human colon cancer cell number. We tested N-terminal TBC1D8B, which is identical to wild type TBC1D8B from amino acid positions 1 to 427 and possesses a modified sequence from position 428 to 435 (ECGGLFLL) because of the introduction of a premature stop codon at position 436 to narrow down the minimum requirement element. The N-terminal TBC1D8B contains two GRAM domains but not the TBC domain essential for Rab-GTPase activity. The N-terminal TBC1D8B overexpression significantly reduced the cultured HCT116 cell number. When we tested C-terminal TBC1D8B, containing the portion of TBC1D8B absent in the N-terminal TBC1D8B, the cell number reduction was not observed. The N-terminal TBC1D8B overexpression significantly increased the coronin 1B expression and reduced the phosphorylation of serine 51 in eIF2α, respective markers of apoptosis and cell death/survival. Also, caspase 3 and poly ADP-ribose polymerase increased cleavage in suspended cells overexpressing the N-terminal TBC1D8B. Taken together, it is not the TBC domain for Rab-GTPase activity, but amino acids 1 to 435, including the two GRAM domains, that is enough for TBC1D8B to cause spontaneous apoptosis. TBC1D8B could be a potential anticancer therapeutic molecule.
Asunto(s)
Apoptosis , Proteínas de Unión al Calcio/fisiología , Proteínas de Transporte Vesicular/fisiología , Antineoplásicos/farmacología , Muerte Celular , Clonación Molecular , Codón de Terminación , Factor 2 Eucariótico de Iniciación/química , Proteínas Activadoras de GTPasa/química , Células HCT116 , Humanos , Fosforilación , Dominios Proteicos , TransfecciónRESUMEN
Free triiodothyronine/free thyroxine (FT3/FT4) ratio is considered as an index of the activities of iodothyronine deiodinase types 1 and 2 (DIO1 and DIO2, respectively) and is reportedly associated with insulin resistance in euthyroid adults. Euthyroid women with polycystic ovary syndrome accompanied with insulin resistance have lesser deiodinase activities. Correspondingly, the serum insulin level in a fasted condition positively correlates with the FT3/FT4 ratio, and insulin depletion decreases the DIO2 activity in mice. Selected genetic variants in DIO1 are also associated with insulin resistance measures. Therefore, if insulin positively regulates DIO1 and DIO2, the FT3/FT4 ratio should decrease under impaired insulin action, and the casual insulin level and FT3/FT4 ratio should be negatively correlated. To evaluate this hypothesis, we conducted a single-center retrospective study between 2018 and 2021. All participants visited the selected hospitals monthly for type 2 diabetes mellitus treatment and casual plasma glucose and HbA1c level measurements. Furthermore, their casual serum insulin levels were measured annually. Meanwhile, we excluded patients treated with insulin injection. Ultimately, we evaluated 71 patients, which all exhibited euthyroid conditions. The FT3/FT4 ratio was independently associated with thyroid-stimulating hormone, casual plasma glucose, and casual insulin levels. In terms of the regression coefficients of the univariate linear regression analysis, the FT3/FT4 ratio negatively correlated with the casual serum insulin levels. Therefore, the risk of FT3/FT4 ratio underestimation should be considered when diagnosing Graves' disease, which is often accompanied with insulin resistance.
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Diabetes Mellitus Tipo 2/sangre , Insulina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Yoduro Peroxidasa/metabolismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Yodotironina Deyodinasa Tipo IIRESUMEN
We recently isolated a novel co-activator of peroxisome proliferator-activated receptor γ, helicase with zinc finger 2 (HELZ2). HELZ2 null mice were resistant to diet-induced obesity and NAFFL/NASH, and HELZ2 was phosphorylated at tyrosine residues. In order to find a factor related to HELZ2, we analyzed products co-immunoprecipitated with phosphorylated HELZ2 by mass spectrometry analyses. We identified proline- and glutamine-rich (SFPQ) as a protein associating with tyrosine-phosphorylated HELZ2. The knockdown of SFPQ in 3T3-L1 cells downregulated mRNA levels of transcription factors including Krox20, Cebpß, and Cebpδ: key factors for early-stage adipocyte differentiation. In addition, knockdown of SFPQ inhibited 3T3-L1 cell differentiation to mature adipocytes. These findings demonstrated that SFPQ associating with HELZ2 is an important novel transcriptional regulator of adipocyte differentiation.
Asunto(s)
Adipocitos/citología , Adipocitos/metabolismo , Diferenciación Celular , Núcleo Celular/metabolismo , PPAR gamma/metabolismo , Factor de Empalme Asociado a PTB/metabolismo , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Células 3T3-L1 , Animales , Regulación de la Expresión Génica , Células HeLa , Humanos , Gotas Lipídicas/metabolismo , Ratones , Fosforilación , Fosfotirosina/metabolismo , Unión Proteica , ARN Interferente Pequeño/metabolismoRESUMEN
Objective: Because patients with diabetes mellitus (DM) were forced to stay indoors during the state of emergency, resulting in stress and a lack of physical activity, concerns about their glycemic control were raised. Patients and Methods: The 165 patients' glycated hemoglobin (HbA1c) levels were compared during the following periods: the 4 months that were selected as a representative condition 1 year before the COVID-19 pandemic (May 2018, March 2019, June 2019, and July 2019) and the latter 3 months as a 1-year follow-up during the COVID-19 pandemic (May 2019, March 2020, June 2020, and July 2020). Results: The patients' HbA1c levels were 7.32 ± 1.23, 7.44 ± 1.20, 7.16 ± 1.06, 7.01 ± 1.05, 7.23 ± 1.06, 7.45 ± 1.18, 7.15 ± 10.7, and 7.11 ± 1.17 in May 2018, March 2019, June 2019, July 2019, May 2019, March 2020, June 2020, and July 2020, respectively (expressed as mean ± standard deviation). Conclusion: The analysis showed that HbA1c levels did not worsen during the self-restraint period.
RESUMEN
Anemia due to angiotensin receptor blocker (ARB) therapy has been previously reported in patients with diabetes mellitus with glomerular filtration rates of <60 mL min-1/1.73 m2. However, whether Japanese patients with type 2 diabetes mellitus (T2DM) receiving ARB therapy for chronic cardiac failure and chronic kidney disease develop reduced hemoglobin (Hb) levels has not been elucidated. Thus, this cross-sectional study was conducted, and Hb levels were compared between patients with T2DM with and without ARB administration. No significant difference in the prescribed proportion of antidiabetic medicines such as biguanide, sodium glucose co-transporter 2 inhibitors, and α-glucosidase inhibitors was found between the group treated with ARBs and the group without ARBs. Thus, we considered that the effects of antidiabetic medicines on the results were minimum. In this study, the Hb levels of patients who received ARBs (13.8 ± 1.7 g/dL) were significantly lower than those of patients without ARBs (14.9 ± 1.35 g/dL) (p = 0.034). The difference between this study and a previous study relies on eGFR levels. Thus, the eGFR levels of the patients in this study and the previous study were above 60 and below 60 mL min-1/1.73 m2, respectively. Despite those differences, both studies showed that the use of ARBs was associated with a decrease in Hb levels in patients with T2DM. Thus, the evaluation of glycated Hb levels should be focused on whether ARBs are prescribed for patients with T2DM.
Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/análisis , Insuficiencia Cardíaca/sangre , Insuficiencia Renal Crónica/sangre , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In this study, we compared the efficacy of a dipeptidyl peptidase-4 inhibitor (DPP4i) to improve glucose control in patients with type 2 diabetes mellitus (T2DM) with or without Hashimoto's thyroiditis (HT). First, we compared the change in glycated hemoglobin (HbA1c) between the hypothyroid condition (before levothyroxine sodium hydrate [LT4] treatment) and euthyroid condition (after LT4 treatment when patients had achieved euthyroidism for at least six months) in patients with T2DM and HT. Next, we compared the change in HbA1c levels before and six months of DPP4i treatment in patients with T2DM with and without HT. In hypothyroid condition the change in HbA1c after six months of DPP4i treatment was 0.13% ± 0.86%. The change in HbA1c levels from when patients first achieved euthyroidism to after six months in the euthyroid condition was 0.26% ± 0.90%. DPP4i efficacy in patients with T2DM and HT was reduced compared to patients with T2DM but without HT (-0.40 ± 0.90 vs. -0.99 ± 0.5, p = 0.0032). These data suggest that hypothyroidism does not impact on DPP4i efficacy. However, the effect of DPP4i in patients with T2DM and HT was reduced compared to that in T2DM patients without HT. An estimation of thyroid function before prescribing DPP4i may be useful tool for predicting the efficacy of DPP4i, allowing the ruling out complications from HT.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Enfermedad de Hashimoto/complicaciones , Hipoglucemiantes/uso terapéutico , Anciano , Anciano de 80 o más Años , Glucemia , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Enfermedad de Hashimoto/sangre , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Although generally considered part of a healthy diet, coffee consumption has been suspected to be associated with elevated epinephrine levels and increasing insulin resistance. OBJECTIVES: We studied the effects of the intake of 3 different types of coffee (Tanzanian, Ethiopian, and Kenyan) on postprandial interstitial glucose levels. METHOD: Interstitial glucose levels were measured every 15 minutes using the FreeStyle Libre glucose monitoring system (Abbott Diabetes Care Ltd, Witney, United Kingdom) in each individual after drinking coffee compared with when not consuming coffee. RESULTS: Unlike Tanzanian and Ethiopian coffees, Kenyan coffee suppressed the increase of postprandial interstitial glucose levels. Kenyan coffee beans contain less anhydrous caffeine and more chlorogenic acid than Tanzanian and Ethiopian coffee beans. These findings may explain the different effects of these coffee types on postprandial interstitial glucose levels. Furthermore, Kenyan coffee beans inhibited α-glucosidase activity, which may partially explain why Kenyan coffee reduces postprandial interstitial glucose levels. CONCLUSIONS: Coffee is widely consumed as a beverage worldwide, and our findings suggest that patients with diabetes mellitus may benefit from drinking Kenyan coffee because of its ability to reduce postprandial interstitial glucose levels. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).
RESUMEN
Brief refeeding times (~60 min) enhanced hepatic Angptl8 expression in fasted mice. We cloned the mouse Angptl8 promoter region to characterise this rapid refeeding-induced increase in hepatic Angptl8 expression. Deletion of the -309/-60 promoter region significantly attenuated basal promoter activity in hepatocytes. A computational motif search revealed a potential binding motif for hepatocyte nuclear factor 1α/1ß (HNF-1α/ß) at -84/-68 bp of the promoter. Mutation of the HNF-1 binding site significantly decreased the promoter activity in hepatocytes, and the promoter carrying the mutated HNF-1 site was not transactivated by co-transfection of HNF-1 in a non-hepatic cell line. Silencing Hnf-1 in hepatoma cells and mouse primary hepatocytes reduced Angptl8 protein levels. Electrophoretic mobility-shift assays confirmed direct binding of Hnf-1 to its Angptl8 promoter binding motif. Hnf-1α expression levels increased after short-term refeeding, paralleling the enhanced in vivo expression of the Angptl8 protein. Chromatin immunoprecipitation (ChIP) confirmed the recruitment of endogenous Hnf-1 to the Angptl8 promoter region. Insulin-treated primary hepatocytes showed increased expression of Angptl8 protein, but knockdown of Hnf-1 completely abolished this enhancement. HNF-1 appears to play essential roles in the rapid refeeding-induced increases in Angptl8 expression. HNF-1α may therefore represent a primary medical target for ANGPTL8-related metabolic abnormalities. The study revealed the transcriptional regulation of the mouse hepatic Angptl8 gene by HNF-1.
Asunto(s)
Proteínas Similares a la Angiopoyetina/genética , Regulación de la Expresión Génica , Factor Nuclear 1 del Hepatocito/genética , Hígado/metabolismo , Transcripción Genética/genética , Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina/metabolismo , Animales , Línea Celular , Inmunoprecipitación de Cromatina , Factor Nuclear 1 del Hepatocito/metabolismo , Hepatocitos/metabolismo , Ratones , Regiones Promotoras GenéticasRESUMEN
The family with sequence similarity 83 (FAM83) protein family G (FAM83G) possesses a predicted consensus phosphorylation motif for serine/threonine-protein kinase D1/protein kinase C mu (PKD1/PKCµ) at serine residue 356 (S356). In this study, overexpressed wild-type FAM83G coimmunoprecipitated with PKD1/PKCµ in Chinese hamster ovary (CHO) cells inhibited heat shock protein 27 (HSP27) phosphorylation at S82 and reduced the living cell number. The expression of a FAM83G phosphorylation-resistant mutant (S356A-FAM83G) had no effect on the living cell number or the induction of spontaneous apoptosis. By contrast, the introduction of a synthetic peptide encompassing FAM83G S356 into HCT116 and HepG2 cells decreased HSP27 S15 and S82 phosphorylation and induced spontaneous apoptosis. On the other hand, the introduction of FAM83G phosphorylation-resistant mutant synthesized peptides (S356A-AF-956 and S356A-AG-066) did not reduce the living cell number or induce spontaneous apoptosis. The endogenous expression of HSP27 and FAM83G was apparently greater in HCT116 and HepG2 cells compared with in CHO cells. In various types of lung cancer cell lines, the FAM83G messenger RNA (mRNA) level in non-small lung cancer cells was at a similar level to that in non-cancerous cells. However, the FAM83G mRNA level in the small cell lung cancer cell lines was variable, and the HSP27 mRNA level in FAM83G mRNA-rich types was greater than that in FAM83G mRNA-normal range types. Taken together, these data demonstrate that FAM83G S356 phosphorylation modulates HSP27 phosphorylation and apoptosis regulation and that HSP27 is a counterpart of FAM83G.
Asunto(s)
Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Oxidorreductasas de Alcohol , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Células HCT116 , Células Hep G2 , Humanos , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Péptidos/síntesis química , Péptidos/química , Péptidos/farmacología , FosforilaciónRESUMEN
Previously, we reported that short-term continuous glucose monitoring (CGM) with the professional iPro2© CGM device is a good clinical indicator of glycated hemoglobin (HbA1c) levels. However, there was no significant correlation between CGM and HbA1c levels when HbA1c levels were >8.0%. To further investigate this issue, we performed a similar study using the FreeStyle Libre Pro©, a newer device that does not require glucose calibration and allows patients to be examined for up to 14 days. Fifty-nine patients (68% women, 32% men) were examined. Twenty-eight and 31 patients presented with type 1 and type 2 diabetes, respectively. Clinically assessed HbA1c levels were compared to blood glucose levels determined by the FreeStyle Libre Pro© for up to 14 days (10.7 ± 3.7 days). We found a significant correlation between HbA1c and CGM levels even when HbA1c levels were >8.0%. Additionally, the correlation between HbA1c and average glucose was identified with the modern CGM and was found to deviate substantially from the new suggested formula. More importantly, we found a more robust correlation between HbA1c and CGM levels in patients with type 2 diabetes. Overestimation or underestimation of blood glucose levels through CGM might increase the risks of inappropriate clinical treatment of diabetes patients. Our results indicate the need for proper CGM data interpretation individualized for each patient to better assist the determination of customized treatments for patients.
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Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/análisis , Adulto , Anciano , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana EdadRESUMEN
The Abbott FreeStyle Libre flash glucose monitoring system (FGM) is a recently introduced, but widespread continuous glucose monitoring system. While its mean absolute relative difference (MARD) value indicating its accuracy is acceptable with reference to the self-monitoring of blood glucose (SMBG) levels, few reports have examined the MARD in sensor glucose values of FGM (FGM-SG) with reference to plasma glucose (PG) levels and the factors determining it. We performed oral glucose tolerance tests (OGTTs) in 25 Japanese subjects without diabetes. Parkes error grid analyses showed that FGM-SG with either SMBG or PG levels as a reference met International Organization for Standardization criteria. The MARD in FGM-SG with reference to SMBG levels was 10.9 ± 4.1% during OGTTs. Surprisingly, the MARD in FGM-SG with reference to PG levels was 20.3 ± 10.3% during OGTTs, revealing a discrepancy in the accuracy of FGM-SG compared with that of PG levels; moreover, the MARD showed negative correlations with fasting blood sugar level, homeostasis model assessment insulin resistance index, and body mass index (BMI). Multiple regression analyses revealed that BMI contributed the most to the MARD when FGM-SG and PG level were compared, as lean individuals have a greater MARD regardless of glucose levels. Inaccurate FGM data could potentially increase the risk of inappropriate treatment; consideration of such factors is critical to ensure reliable FGM values.