Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
1.
Chem Commun (Camb) ; 57(68): 8500-8503, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34351333

RESUMO

Transition-metal-free acid-promoted biaryl construction was achieved via intermolecular C-F/C-H cross-coupling. By treating 2-fluorobenzofurans with arenes in the presence of AlCl3, 2-arylbenzofurans were obtained. This protocol was successfully applied to the short-step orthogonal synthesis of a bioactive 2-arylbenzofuran natural product, which allows independent transformations of C-F and C-Br bonds. Mechanistic studies indicated that α-fluorine-stabilized carbocations, generated via the protonation of 2-fluorobenzofurans, served as key intermediates. The Friedel-Crafts-type C-C bond formation between the α-fluorocarbocations and arenes, followed by hydrogen fluoride elimination, afforded 2-arylbenzofurans.

2.
Nutrients ; 13(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34371843

RESUMO

The aim of this prospective cohort study was to examine the relationships between the intakes of various vitamins and the loss of muscle mass in older people with type 2 diabetes (T2DM). The change in skeletal muscle mass index (SMI, kg/m2) (kg/m2/year) was defined as follows: (SMI at baseline (kg/m2) - SMI at follow-up (kg/m2))/follow-up period (year). The rate of SMI reduction (%) was calculated as follows (the change in SMI (kg/m2/year)/SMI at baseline (kg/m2)) × 100. The rate of SMI reduction ≥ 1.2% was considered as the loss of muscle mass. Among 197 people with T2DM, 47.2% of them experienced the loss of muscle mass at the 13.7 ± 5.2 month follow-up. Vitamin B1 (0.8 ± 0.3 vs. 0.8 ± 0.3 mg/day, p = 0.031), vitamin B12 (11.2 ± 8.3 vs. 13.4 ± 7.5 µg/day, p = 0.049), and vitamin D (16.5 ± 12.2 vs. 21.6 ± 13.0 µg/day, p = 0.004) intakes in people with the loss of muscle mass were significantly lower than those without. Vitamin D intake was related to the loss of muscle mass after adjusting for sex, age, exercise, alcohol, smoking, body mass index, SMI, glucagon-like peptide-1 agonist, sodium glucose cotransporter-2 inhibitor, insulin, HbA1c, creatinine, energy intake, and protein intake (adjusted odds ratio 0.93, 95% confidence interval: 0.88-0.97, p = 0.003). This study showed that vitamin D intake was related to the loss of muscle mass in older people with T2DM. Vitamin B12 intake tended to be related to the loss of muscle mass, although vitamin A, vitamin B2, vitamin B6, vitamin C, and vitamin E intake were not related.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Dieta/efeitos adversos , Estado Nutricional , Sarcopenia/epidemiologia , Vitaminas/análise , Idoso , Diabetes Mellitus Tipo 2/complicações , Dieta/estatística & dados numéricos , Inquéritos sobre Dietas , Ingestão de Energia/fisiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Músculo Esquelético/fisiopatologia , Estudos Prospectivos , Sarcopenia/etiologia
3.
Front Immunol ; 12: 648754, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790913

RESUMO

Background and Aims: Emerging evidence has revealed that innate lymphoid cells (ILCs) play a key role in regulating metabolic disorders. Here, we investigated the role of group 3 ILCs (ILC3s) in the modulation of Non-alcoholic fatty liver disease (NAFLD). Methods: RORγ gfp/gfp (RORgt KI/KI) and Rag2-/- mice with the administration of A213, RORgt antagonist, fed with a high-fat-diet (HFD) for 12 weeks, were used. We performed flow cytometry, real time PCR, and lipidomics analysis of serum and liver, and used RAW264.7 cells and murine primary hepatocytes in vitro. Results: HFD increased ILC3s and M1 macrophages in the liver, and RORgt KI/KI mice deficient in ILC3 showed significant fatty liver, liver fibrosis and significantly increased palmitic acid levels in serum and liver. In addition, administration of A213 to Rag2-/- mice caused significant fatty liver, liver fibrosis, and a significant increase in serum and liver palmitate concentrations, as in RORgt KI/KI mice. Addition of palmitc acid stimulated IL-23 production in cell experiments using RAW264.7. IL-22 produced by ILC3s inhibited the palmitate-induced apoptosis of primary hepatocytes. Conclusions: HFD stimulates IL-23 production by M1 macrophages, thus promoting ILC3 proliferation, whereas IL-22 secreted by ILC3s contributes to the upregulation of hepatic lipid metabolism and has anti-apoptosis activity.


Assuntos
Fígado Gorduroso/imunologia , Imunidade Inata/imunologia , Fígado/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Animais , Apoptose/imunologia , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Hepatócitos/citologia , Hepatócitos/imunologia , Fígado/metabolismo , Fígado/patologia , Linfócitos/metabolismo , Macrófagos/classificação , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ácido Palmítico/sangue , Ácido Palmítico/imunologia , Ácido Palmítico/metabolismo , Substâncias Protetoras/metabolismo , Células RAW 264.7
4.
Can J Diabetes ; 44(5): 428-433, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32616276

RESUMO

OBJECTIVES: Previous studies have shown the association between liver fibrosis and albuminuria. However, the effect of liver fibrosis on change in albuminuria is unclear. Thus, we investigated the effect of liver fibrosis on change in albuminuria in patients with type 2 diabetes. METHODS: In this retrospective cohort study, we assessed 105 patients with type 2 diabetes concomitant with nonalcoholic fatty disease. A change in urinary albumin excretion (UAE) was defined as follows: change in UAE=(logarithm [UAE+1] at follow-up examination minus logarithm [UAE+1] at baseline examination) / follow-up duration (1 year in this study). Elastography was performed to assess controlled attenuation parameter (dB/m) and liver stiffness measurement (LSM; kPa) values. RESULTS: Mean (standard deviation) data were as follows: age, 63.3 (12.1) years; body mass index, 25.4 (4.3) kg/m2; controlled attenuation parameter, 273.1 (53.0) dB/m; and LSM, 6.2 (3.4) kPa. Median UAE value (interquartile range) was 16 (6 to 43) mg/g creatinine. LSM was associated with changes in UAE (r=0.27, p=0.005). Multiple regression analysis demonstrated that LSM was associated with change in UAE (ß=0.28, p=0.015) after adjusting for sex, age, duration of diabetes, smoking status, exercise habits, glycated hemoglobin, body mass index, estimated glomerular filtration rate, systolic blood pressure, logarithm (UAE+1) at baseline examination, use of renin‒angiotensin system inhibitors, new use of sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 and controlled attenuation parameter. CONCLUSIONS: Liver stiffness is an independent risk factor for the progression of albuminuria in patients with type 2 diabetes.


Assuntos
Albuminúria/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Idoso , Albuminúria/etiologia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Progressão da Doença , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações
5.
Am J Physiol Gastrointest Liver Physiol ; 318(6): G989-G999, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32363890

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Orchiectomized (OCX) male Rag2-/- mice were used as a model of testosterone deficiency. To assess NAFLD severity, NAFLD activity score (NAS) is adopted. Moreover, immunological change was analyzed by multicolor flow cytometry. Treatment with both testosterone and estrogen significantly decreased body weight to that of the sham mice/normal diet (ND). NAS and liver fibrosis in OCX-HFD mice were significantly deteriorated, and treatment with testosterone and estrogen improved same as sham-ND mice. HFD increased the ratio of both type 2 and 3 innate lymphoid cells (ILC2s and ILC3s) to CD45-positive cells in the liver. Treatment with testosterone alone decreased the ratio of ILC2 to CD45 but not the ILC3-to-CD45 ratio. Addition of estrogen to the treatment reduced the ratios of ILC2-to-CD45 and ILC3-to-CD45 to the same level observed in sham-HFD mice. Moreover, OCX-HFD mice had a decreased proportion of M2 macrophages compared with sham-ND mice. Treatment with testosterone alone did not restore the proportion of M2 macrophages; however, combination treatment with both estrogen and testosterone increased that to the same level as that in sham-HFD mice. Treatment with both testosterone and estrogen improves liver fibrosis and decreases ILC3 and increases M2 macrophage abundance in the liver.NEW & NOTEWORTHY The progression of nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. NAFLD patients generally do not respond to treatment with testosterone alone. In animal studies, treatment with testosterone and estrogen reduced the ratios of ILC2:CD45 and ILC3:CD45 and increased M2 macrophages in liver. Our study suggests, based on our immunological data, that a combination of estrogen and testosterone may be clinically relevant for the treatment of NAFLD in patients with male menopause.


Assuntos
Estradiol/farmacologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Testosterona/farmacologia , Aminoácidos , Animais , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Cromo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo , Estradiol/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Insulina , Cirrose Hepática , Neoplasias Hepáticas , Masculino , Camundongos , Camundongos Knockout , Ácidos Nicotínicos , Hepatopatia Gordurosa não Alcoólica/patologia , Orquiectomia , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CCR2/genética , Receptores CCR2/metabolismo , Testosterona/administração & dosagem , Testosterona/deficiência , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
6.
Molecules ; 25(7)2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32260359

RESUMO

Thrombopoietin (THPO) is a circulatory cytokine that plays an important role in platelet production. The presence of anti-THPO antibody relates to thrombocytopenia and is rarely seen in hematopoietic and autoimmune diseases. To date, there had been no reports that focused on the anti-THPO antibody in patients with type 2 diabetes mellitus (T2DM). To evaluate prevalence of the anti-THPO antibody in patients with T2DM and the relationship between anti-THPO antibody and platelet count, a cross-sectional study was performed on 82 patients with T2DM. The anti-THPO antibody was measured by ELISA using preserved sera and detected in 13 patients. The average platelet count was significantly lower in patients with the anti-THPO antibody than in those without the anti-THPO antibody. Multivariate linear regression analyses showed a significant relationship between the anti-THPO antibody and platelet count, after adjusting for other variables. To our best knowledge, this was the first report on the effect of the anti-THPO antibody on platelet count in patients with T2DM. Further investigation is needed to validate the prevalence and pathological significance of the anti-THPO antibody in patients with T2DM.


Assuntos
Anticorpos/sangue , Diabetes Mellitus Tipo 2/sangue , Trombopoetina/imunologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Contagem de Plaquetas , Análise de Regressão
7.
J Endocrinol ; 244(3): 535-547, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31958315

RESUMO

To investigate the role of microRNA (miRNA) in muscle atrophy, we performed microarray analysis of miRNA expression in skeletal muscles of Sham, orchiectomized (ORX) mice, and ORX mice treated with androgen and identified that the expression of miR-23b-3p in ORX mice was significantly higher than that in Sham mice (P = 0.007); however, miR-23b-3p expression in ORX mice treated with androgen was lower (P = 0.001). We also investigated the mechanism by which overexpression or knockdown of miR-23b-3p influences the expression of myosin heavy chain, muscle protein synthesis, ATP activity, and glucose uptake in C2C12 myotube cells. Moreover, we examined the serum miR-23b-3p levels among male subjects with type 2 diabetes and whether the serum miR-23b-3p levels could be a biomarker for muscle atrophy. The overexpression of miR-23b-3p in C2C12 myotube cells significantly upregulated the expression of myosin heavy chain, protein synthesis, ATP activity, and glucose uptake. Reporter assays raised a possible direct post-transcriptional regulation involving miR-23b-3p and the 3'-UTR of PTEN mRNA. Among subjects with type 2 diabetes, serum miR-23b-3p levels in the subjects with decreased muscle mass were significantly higher compared to the levels in the subjects without. Our results indicate that miR-23b-3p downregulates the expression of PTEN in myotube cells and induces the growth of myosin heavy chain. In addition, the serum level of miR-23b-3p can be used as a diagnostic marker for muscle atrophy.


Assuntos
MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Trifosfato de Adenosina/metabolismo , Androgênios/administração & dosagem , Animais , Estudos de Coortes , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/genética , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo
8.
J Diabetes Investig ; 11(3): 626-632, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31659860

RESUMO

AIMS/INTRODUCTION: In Japan, an ideal bodyweight (IBW) calculated by 22 × height (m)2 has commonly been used in the planning of medical nutrition therapy (MNT). However, there have been concerns regarding calorie deficits in fulfilling resting energy expenditure (REE) for patients with type 2 diabetes undergoing MNT as defined by 25 kcal/kg IBW/day. The objective of the present study was to measure REE in patients with type 2 diabetes and verify the validity of MNT with 25 kcal/kg IBW/day. MATERIALS AND METHODS: A retrospective cross-sectional study was carried out in 52 patients with type 2 diabetes (mean age was 65.9 ± 7.3 years, bodyweight 65.0 ± 11.3 kg, body mass index 24.9 ± 3.8 kg/m2 ). REE was measured by indirect calorimetry. RESULTS: The mean REE was 1,601.0 ± 253.1 kcal/day. Assuming that all patients strictly observed daily energy intake as 25 kcal/kg IBW/day, 41 of 52 patients (78.9%) did not reach their REE. The greater the bodyweight, the greater the difference between assumed energy intake as 25 kcal/kg IBW and REE. CONCLUSIONS: We call attention to the potential risk of total dietary energy intake set to 25 kcal/kg IBW/day. Clinicians should carefully plan MNT to not fall below a patient's REE to prevent sarcopenia and ensure MNT continuity.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/metabolismo , Ingestão de Energia , Metabolismo Energético , Terapia Nutricional/métodos , Idoso , Índice de Massa Corporal , Calorimetria Indireta , Estudos Transversais , Feminino , Humanos , Peso Corporal Ideal , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
J Clin Med ; 8(12)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31835362

RESUMO

Body weight reduction leads to improvement of nonalcoholic fatty liver disease (NAFLD), but the contributions of body composition modification on its improvement have not been clarified yet. We performed a retrospective cohort study in a Japanese university hospital to clarify the effect of body fat reduction on the improvement of hepatic stiffness as well as hepatic steatosis. The skeletal muscle mass index (SMI, kg/m2), fat to muscle mass ratio, and the change in fat to muscle mass ratio after 1 year from baseline were calculated. Controlled attenuation parameter (CAP, dB/m) and liver stiffness measurement (LSM, kPa) were evaluated by elastography. Primary outcome was set as the association of the change of fat to muscle mass ratio after 1 year from baseline with the change of liver stiffness measurement. One hundred and seventeen patients (59 men and 58 women) completed the study. The average age was 63.5 years, and baseline CAP and LSM were 273.4 ± 53.5 dB/m and 6.3 ± 3.4 kPa, respectively. After 1 year, body mass index (BMI), SMI, and LSM decreased. Multiple regression analyses demonstrated that change in fat to muscle mass ratio was associated with the change in CAP (ß = 0.38, p < 0.001) or LSM (ß = 0.21, p = 0.026). The reduction of fat to muscle mass ratio was associated with improvement in liver stiffness, but the reduction of BMI was not.

10.
J Clin Biochem Nutr ; 65(1): 23-28, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31379410

RESUMO

We investigated the effect of the sodium glucose cotransporter-2 inhibitor (SGLT-2i) luseogliflozin on skeletal muscle. Eight-week-old mice were fed a standard diet or the standard diet with added luseogliflozin for 8 weeks. The mice were divided into the following four genotype/dietary groups: Db/m mice without SGLT-2i, Db/m mice with SGLT-2i inhibitor, Db/Db without SGLT-2i, and Db/Db with SGLT-2i. Among the mice with and without SGLT-2i, the ratio of soleus and plantaris muscle to body weight in the Db/Db mice was significantly lower than that in the Db/m mice. The cross-sectional area of soleus muscle in the Db/Db mice without SGLT-2i was significantly higher than that in the Db/Db mice with SGLT-2i. The expression of foxo1 in soleus muscle of the Db/Db mice was significantly higher than that of the Db/m mice, and the foxo1 expression of the Db/Db mice with SGLT-2i was significantly lower than that of the mice without SGLT-2i. The fluorescence intensity of foxo1 in the Db/Db mice fed SGLT-2i was significantly lower than that in the Db/Db mice without SGLT-2i. The administration of luseogliflozin resulted in the suppression of both the increased foxo1 expression and the reduced muscle cross-sectional area in the soleus muscle of Db/Db mice.

11.
J Diabetes Investig ; 10(4): 947-950, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30414308

RESUMO

Whole-exome sequencing is a new technology. We used it to explore the gene responsible for early-onset diabetes as a result of impaired insulin secretion in a family. In the INS gene, we identified the heterozygous c.188-31G>A mutation in the proband - a 43-year-old woman. The mutation was also identified in her two daughters with diabetes, but not in her son or her parents, all of whom did not have diabetes. The substitution was located 31 bp proximal to exon 3 in intron 2. It was predicted to create an ectopic splice site leading to inserting 29 nucleotides of intron 2 as an exonic sequence in the transcript. The mutation has been reported in White families, and the present case is the first report in an Asian person. The present results would help in understanding the role of the mutation in developing diabetes.


Assuntos
Biomarcadores/análise , Diabetes Mellitus/genética , Insulinas/genética , Íntrons , Mutação , Sequenciamento Completo do Exoma/métodos , Adulto , Idade de Início , Criança , Pré-Escolar , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/patologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Linhagem , Prognóstico
12.
Tissue Eng Part A ; 25(3-4): 183-192, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30280968

RESUMO

IMPACT STATEMENT: Although transplantation of islets of Langerhans has been accepted as a fundamental treatment for insulin-dependent diabetes mellitus (IDDM), several problems are still remaining in order that it becomes the standard medical treatment of IDDM patients. In this study, using diabetic rat models, a subcutaneous space surrounded with highly vascularized granulomatous tissue was formed by agarose-bFGF rod implantation. Allogeneic islets transplanted into the space could survive and release insulin for a long period under no immunosuppressive medication. In conjunction with sufficient supply of islets from iPS/ES cells, our method can make islet transplantation the standard medical treatment of IDDM patients.


Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Secreção de Insulina , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/metabolismo , Pele , Tela Subcutânea , Animais , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Wistar
13.
J Clin Biochem Nutr ; 63(2): 106-112, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30279621

RESUMO

Dipeptidyl peptidase-4 (DPP-4) is a critical molecule for the metabolism of incretins. In addition, DPP-4 is known as CD26, the receptor of T cells, and plays important role in activation of T cells. Recently, DPP-4 inhibitors (DPP4i) are reported to have several immunologic effects beyond glycemic control. DPP4i seem to have anti-inflammatory effects in patients with type 2 diabetes. This might be direct effects on T cells. However, the close mechanism is not clear. To evaluate the possibility, we performed ex vivo assays by using primarily human CD4+ T cells (CD4) and CD8+ T cells (CD8). We purified primary naïve CD4 and CD8 from human peripheral blood. Then, we evaluated the effect of DPP4i on the proliferation of naïve T cells and the cytokine production in ex vivo experiments. The proliferation of CD4 and CD8 were suppressed by adding DPP4i in a dose dependent manner. However, DPP4i did not inhibit cytokine production from CD4. It was revealed by phospho-flow that the T cell receptor (TCR) signaling was attenuated in the presence of DPP4i. Taken together, DPP4i modulated TCR signaling, which contributed to attenuate the proliferation of CD4 and CD8. DPP4i have adverse effects for the proliferation of human T cells.

14.
Sci Rep ; 8(1): 4029, 2018 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-29507299

RESUMO

Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress. Analysis of glomerular phenotypes using glomeruli isolation demonstrated that ipragliflozin preserved podocyte integrity and reduced oxidative stress. Regarding renal tissue hypoxia, a short-term ipragliflozin treatment improved oxygen tension in the kidney cortex, in which SGLT2 is predominantly expressed. We then administered ipragliflozin to type 1 diabetic mice and found that high- and low-dose ipragliflozin both reduced urinary albumin excretion. In conclusion, we confirmed dose-dependent differences in the effects of ipragliflozin on early diabetic nephropathy in vivo. Even low-dose ipragliflozin reduced renal cortical hypoxia and abnormal hemodynamics in early diabetic nephropathy. In addition to these effects, high-dose ipragliflozin exerted renoprotective effects by reducing oxidative stress in tubular epithelia and glomerular podocytes.


Assuntos
Glucosídeos/farmacologia , Rim/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Tiofenos/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C
15.
Endocr J ; 65(4): 395-402, 2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29375081

RESUMO

Skipping breakfast or irregular breakfast is associated with poor glycemic control. However, a relationship between the timing of dinner and glycemic control in people with type 2 diabetes remains indefinite. Therefore, we investigated the relationship between late-night-dinner and glycemic control in people with type 2 diabetes. We performed questionnaire survey for lifestyle factors in this cross-sectional study. We defined having dinner later than eight pm as late-night-dinner. We examined the differences in clinical and metabolic parameters between those who have late-night-dinner and those who do not have. We also examined the relationship between late-night-dinner and HbA1c, using multiple regression analysis. Ninety-five people (23.2%) had a late-night-dinner, among 409 people with type 2 diabetes. Metabolic parameters (mean (SD) or median (interquartile range)) of people with late-night-dinner were worse than those of without, including body mass index (BMI) (24.4 (4.0) vs. 23.2 (3.4) kg/m2, p = 0.006), triglycerides (1.5 (1.1-2.1) vs. 1.2 (0.8-1.7) mmol/L, p < 0.001), HDL-cholesterol (1.4 (0.4) vs. 1.6 (0.4) mmol/L, p = 0.004) and hemoglobin A1c (58.1 (13.3) vs. 55.2 (10.2) mmol/mol, (7.5 (1.2) vs. 7.2 (0.9) %), p = 0.023)). Late-night-dinner (standardized regression coefficient = 0.13, p = 0.028) was associated with hemoglobin A1c after adjusting for age, BMI, sex, duration of diabetes, smoking, exercise, alcohol, snacking after dinner, nighttime sleep duration, time from dinner to bedtime, skipping breakfast, and medication for diabetes. Late-night-dinner is independently associated with poor glycemic control in people with type 2 diabetes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Refeições/fisiologia , Idoso , Índice de Massa Corporal , HDL-Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade
16.
Transplantation ; 102(3): 417-425, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28858989

RESUMO

BACKGROUND: There exists a need for a minimally invasive method of islet transplantation without immunosuppressive drugs for the treatment of type 1 diabetes. METHODS: In diabetic August Copenhagen Irish rats, an agarose rod containing the cyclic oligopeptide SEK-1005 (agarose-SEK rod) was implanted at 2 dorsal subcutaneous sites. Then these rods were removed, and 1500 islets of Langerhans isolated from Fischer 344 rats were transplanted into each of the pockets. RESULTS: Ten days after implantation of agarose-SEK rods, vascularized pockets were present. Nonfasting blood glucose levels confirmed long-term survival of the allogeneic islet grafts, without immunosuppressive therapy, in 8 of 10 recipients. Flow cytometry and gene expression analyses were performed to investigate the mechanisms underlying graft acceptance. Agarose-SEK rod implantation led to the formation of granulomatous tissue containing regulatory T cells that suppressed immune reactions against the allogeneic islet grafts. CONCLUSIONS: These results indicate that the use of an agarose-SEK rod to prevascularize a subcutaneous site may be a useful method for achieving successful allogeneic islet transplantation without immunosuppression.


Assuntos
Imunossupressores/farmacologia , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/fisiologia , Peptídeos Cíclicos/farmacologia , Tela Subcutânea/irrigação sanguínea , Animais , Masculino , Ratos , Ratos Endogâmicos ACI , Ratos Endogâmicos F344 , Transplante Homólogo
17.
J Diabetes Res ; 2017: 7985728, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29209633

RESUMO

Background/Aims: Protein intake is important for maintaining muscle mass in general population. However, it remains to be elucidated the association between dietary protein intake and skeletal muscle mass in elderly patients with type 2 diabetes. Methods: In this cross-sectional study of 168 elderly patients with type 2 diabetes, we investigated the relationship between skeletal muscle index (SMI) and protein intake. Bioimpedance analysis was used for measurement for skeletal muscle mass (kg) and SMI (%), which was defined as skeletal muscle mass (kg)/total body weight (kg) × 100. Habitual food and nutrient intake were estimated by a questionnaire. Results: Protein intake was independently correlated with SMI after adjusting for age, hemoglobin A1c, C-peptide index, exercise, smoking, insulin treatment, total energy intake, and C-reactive protein (standardized regression coefficient = 0.664, P < 0.001 in men and standardized regression coefficient = 0.516, P = 0.005 in women). Additionally, the animal protein to vegetable protein ratio was negatively correlated with SMI after adjusting for covariates in men (standardized regression coefficient = -0.339, P = 0.005). Conclusions: We found that total protein intake, especially vegetable protein intake, was positively associated with skeletal muscle mass in elderly patients with type 2 diabetes.


Assuntos
Composição Corporal/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Proteínas na Dieta , Músculo Esquelético/fisiopatologia , Proteínas de Vegetais Comestíveis , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Peso Corporal , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Masculino , Estado Nutricional , Inquéritos e Questionários , Verduras
18.
Endocrine ; 58(2): 253-261, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28965186

RESUMO

PURPOSE: Metabolic syndrome (MetS), regardless of the presence of obesity, is known as a risk of diabetes and cardiovascular disease. Weight gain after age 20 reported to be associated with these diseases. Impact of the difference between the body mass index (BMI) at examination and BMI at age 20 (ΔBMIexa-20y) on MetS, especially in non-overweight individuals, remains to be elucidated. METHODS: We analyzed the data of 24,363 individuals (14,301 men and 10,062 women) in this cross-sectional study. The diagnosis of MetS was diagnosed when three or more of the following criteria were present: hypertension, hyperglycemia, hypertriglyceridemia, low HDL-cholesterol level, and abdominal obesity. Logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, alcohol, smoking, exercise, and BMI at examination. RESULTS: Compared to the lowest ΔBMIexa-20y tertile (ΔBMIexa-20y < 1.2 kg/m2 in men and ≤0 kg/m2 in women), the highest tertile (ΔBMIexa-20y ≥ 3.2 kg/m2 in men and ≥2.0 kg/m2 in women) was associated with the risk of the presence of MetS (multivariate OR = 1.80, 95%CI 1.53-2.11, p < 0.001 in men and OR = 3.27, 95%CI 2.22-4.96, p < 0.001 in women). This result was also applicable in non-overweight individuals (multivariate OR = 2.06, 95%CI 1.46-2.92, p < 0.001 in men and OR = 2.49, 95%CI 1.40-4.64, p < 0.001 in women). CONCLUSIONS: Our analyses showed that ΔBMIexa-20y is associated with the risk of the presence of MetS, even in non-overweight individuals. It is thus important to check weight changes from early adulthood, even in non-overweight individuals.


Assuntos
Hiperglicemia/complicações , Hipertensão/complicações , Hipertrigliceridemia/complicações , Síndrome Metabólica/etiologia , Obesidade Abdominal/complicações , Ganho de Peso/fisiologia , Adulto , Índice de Massa Corporal , Peso Corporal/fisiologia , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Hiperglicemia/sangue , Hipertensão/sangue , Hipertrigliceridemia/sangue , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Fatores de Risco , Adulto Jovem
19.
Am J Hypertens ; 30(10): 993-998, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911025

RESUMO

BACKGROUND: The aim of this study was to evaluate whether the mean and the variability of home blood pressure (HBP) from the logbook correlate with albuminuria as well as HBP from the stored memory in patients with type 2 diabetes. METHODS: This study is a post hoc analysis of a cross-sectional multicenter study. HBP measurements were performed for 14 consecutive days in 276 patients with type 2 diabetes. Patients were requested to write down their HBP values in logbooks and were not informed about the memory function of their BP monitoring devices. RESULTS: HBP values from the logbook were significantly lower and less variable than those from the stored memory. The mean of morning systolic BP (SBP) from the logbook (adjusted ß = 0.326, P < 0.001) as well as that from the stored memory (adjusted ß = 0.336, P < 0.0001) was significantly associated with logarithm of urinary albumin excretion (UAE). The SD of morning SBP (adjusted ß = 0.134, P = 0.017) from the stored memory was significantly associated with logarithm of UAE, in contrast, the SD of morning SBP (adjusted ß = 0.104, P = 0.057) from the logbook was not associated with logarithm of UAE. CONCLUSIONS: Patients with type 2 diabetes might report inaccurate HBP measurements and, as a result, the variability of HBP from the logbook is underestimated and poorly correlates with albuminuria. The use of stored BP measurements is recommended to accurately evaluate the relationship with diabetic nephropathy.


Assuntos
Albuminúria/fisiopatologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Hipertensão/fisiopatologia , Idoso , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo
20.
Endocr J ; 64(11): 1105-1114, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-28867686

RESUMO

Fatty liver disease and metabolic syndrome (MetS) are both shown to increase the risk of type 2 diabetes. The aim of this study was to investigate the combined effect of fatty liver and MetS on incident diabetes. In this cohort study of 17,810 participants, fatty liver was diagnosed by abdominal ultrasonography and MetS was defined by a joint interim statement. We divided the participants into four groups according to the presence of fatty liver and/or MetS. Type 2 diabetes was defined as HbA1c ≥6.5%, fasting plasma glucose ≥7.0 mmol/L or treatment for diabetes. During the follow up examination (median 5.1 years), 804 participants developed diabetes. Compared with non-MetS without fatty liver, hazard ratios (HR) for incident diabetes after adjusting for age, body mass index, smoking status, exercise habit, alcohol consumption, family history of diabetes logarithm of alanine aminotransferase and fasting plasma glucose, were as follow: 2.35 (95 % CI 1.91-2.89, p<0.001) in non-MetS with fatty liver, 1.70 (95% CI 1.30-2.20, p<0.001) in MetS without fatty liver, and 2.33 (95% CI 1.85-2.94, p<0.001) in MetS with fatty liver. In addition, adjusted HRs for incident diabetes compared with MetS without fatty liver were 1.39 (95% CI 1.07-1.80, p=0.012) in non-MetS with fatty liver and 1.38 (95% CI 1.07-1.79, p=0.013) in MetS with fatty liver. Fatty liver affects more on the risk of incident diabetes than MetS. To prevent the further risk of diabetes, we should pay more attention to fatty liver.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Fígado Gorduroso/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Coortes , Fígado Gorduroso/complicações , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...