Type 2 diabetes is one of the most prevalent and serious metabolic diseases.Under diabetic conditions,chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreaticβ-cell function,which lea...Type 2 diabetes is one of the most prevalent and serious metabolic diseases.Under diabetic conditions,chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreaticβ-cell function,which leads to the aggravation of type 2 diabetes.Although such phenomena are well known as glucose toxicity,its molecular mechanism remains unclear.In this review article,we describe the possible molecular mechanism forβ-cell dysfunction found in type 2 diabetes,focusing on(1)oxidative stress,(2)pancreatic transcription factors(PDX-1 and MafA)and(3)incretin receptors(GLP-1 and GIP receptors).Under such conditions,nuclear expression levels of PDX-1 and MafA are decreased,which leads to suppression of insulin biosynthesis and secretion.In addition,expression levels of GLP-1 and GIP receptors are decreased,which likely contributes to the impaired incretin effects found in diabetes.Taken together,it is likely that downregulation of pancreatic transcription factors(PDX-1and MafA)and down-regulation of incretin receptors(GLP-1 and GIP receptors)explain,at least in part,the molecular mechanism forβ-cell dysfunction found in type 2 diabetes.展开更多
Abdominal obesity,rather than total amount of fat,is linked to obesity-related disorders.Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposit...Abdominal obesity,rather than total amount of fat,is linked to obesity-related disorders.Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposity compared with Western subjects.In 1983,our group reported techniques for body fat analysis using computed tomography(CT)and established the concept of visceral fat obesity in which intra-abdominal fat accumulation is an important factor in the development of obesity-related complications,such as diabetes,lipid disorders,hypertension and atherosclerosis.Our group also established ideal imaging conditions for determining abdominal fat area at the umbilical level CT scan.Visceral fat area(VFA)measured in a single slice at L4level correlated significantly with the total abdominal visceral fat volume measured on multislice CT scan.In a large-scale study of a Japanese population,the mean number of obesity-related cardiovascular risk factors(hypertension,low high-density lipoprotein cholesterolemia and/or hypertriglyceridemia,and hyperglycemia)was greater than 1.0 at 100 cm2 of VFA,irrespective of gender,age and body mass index.Our group also demonstrated that reduction of visceral fat accumulation subsequent to voluntary lifestyle modification,"Hokenshido",correlated with a decrease in the number of obesity-related cardiovascular risk factors.It is important to select the most appropriate subjects from the general population(e.g.,non-obese subjects with a cluster of risk factors for the metabolic syndrome)that are most suitable for body weight reduction,with the goal of preventing atherosclerotic cardiovascular diseases.展开更多
AIM:To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model,and to determine the con-tribution of adiponectin defi ciency to colorectal cancer dev...AIM:To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model,and to determine the con-tribution of adiponectin defi ciency to colorectal cancer development and proliferation.METHODS:We examined the influence of adiponectin defi ciency on colorectal carcinogenesis induced by the administration of azoxymethane(AOM)(7.5 mg/kg,in-traperitoneal injection once a week for 8 wk),by using adiponectin-knockout(KO) mice.RESULTS:At 53 wk after the fi rst AOM treatment,KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type(WT) mice,although the tumor incidence was not different between WT and KO mice.KO mice showed increased cell proliferation of colorec-tal tumor cells,which correlated with the expression levels of cyclooxygenase-2(COX-2) in the colorectal tumors.In addition,KO mice showed higher incidence and frequency of liver tumors after AOM treatment.Thirteen percent of WT mice developed liver tumors,and these WT mice had only a single tumor.In contrast,50% of KO mice developed liver tumors,and 58% of these KO mice had multiple tumors.CONCLUSION:Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice.This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.展开更多
AIM： To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide （LPS） -induced liver injury.METHODS： D-galactosamine （GAIN） and LPS were injected intraperitonea...AIM： To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide （LPS） -induced liver injury.METHODS： D-galactosamine （GAIN） and LPS were injected intraperitoneally into adiponectin-/- mice and wild type mice. Kupffer cells, isolated from Sprague-Dawley rats, were preincubated with or without adiponectin, and then treated with LPS.RESULTS： In knockout mice, GalN/LPS injection significantly lowered the survival rate, significantly raised the plasma levels of alanine transaminase and tumor necrosis factor-α （TNF-α） and significantly reduced IL-10 levels compared with wild type mice. TNF-α gene expression in the liver was which higher and those of IL-10 were lower in knockout mice than in wild type mice. In cultured adiponectin-pre-treated Kupffer cells, LPS significantly lowered TNF-α levels and raised IL-10 levels in the culture media and their respective gene expression levels, compared with Kupffer cells without adiponectinpre-treatment.CONCLUSION： Adiponectin supresses TNF-α production and induces IL-10 production by Kupffer cells in response to LPS stimulation, and a lack of adiponectin enhances LPS-induced liver injury.展开更多
The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedsidetype artificial endocr...The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedsidetype artificial endocrine pancreas is now available in Japan: STG-22 (Nikkiso Co. Ltd., Japan). In the insulin infusion algorithm, insulin is infused on the basis ofits proportional and derivative actions, to blood glucose concentrations with a constant time delay. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetes mellitus, but also as an elegant research tool for investigating the pathophysiology of the disease, by using the euglycemic hyperinsulinemic glucose clamp technique. The wearable type of closed-loop system has been developed recently. The breakthrough is the establishment of a needle-type glucose sensor. The development of closed-loop glycemic control systems that enable long-term physiological regulation has focused on implantable devices. Much effort has been expended to realize these devices.展开更多
文摘Type 2 diabetes is one of the most prevalent and serious metabolic diseases.Under diabetic conditions,chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreaticβ-cell function,which leads to the aggravation of type 2 diabetes.Although such phenomena are well known as glucose toxicity,its molecular mechanism remains unclear.In this review article,we describe the possible molecular mechanism forβ-cell dysfunction found in type 2 diabetes,focusing on(1)oxidative stress,(2)pancreatic transcription factors(PDX-1 and MafA)and(3)incretin receptors(GLP-1 and GIP receptors).Under such conditions,nuclear expression levels of PDX-1 and MafA are decreased,which leads to suppression of insulin biosynthesis and secretion.In addition,expression levels of GLP-1 and GIP receptors are decreased,which likely contributes to the impaired incretin effects found in diabetes.Taken together,it is likely that downregulation of pancreatic transcription factors(PDX-1and MafA)and down-regulation of incretin receptors(GLP-1 and GIP receptors)explain,at least in part,the molecular mechanism forβ-cell dysfunction found in type 2 diabetes.
文摘Abdominal obesity,rather than total amount of fat,is linked to obesity-related disorders.Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposity compared with Western subjects.In 1983,our group reported techniques for body fat analysis using computed tomography(CT)and established the concept of visceral fat obesity in which intra-abdominal fat accumulation is an important factor in the development of obesity-related complications,such as diabetes,lipid disorders,hypertension and atherosclerosis.Our group also established ideal imaging conditions for determining abdominal fat area at the umbilical level CT scan.Visceral fat area(VFA)measured in a single slice at L4level correlated significantly with the total abdominal visceral fat volume measured on multislice CT scan.In a large-scale study of a Japanese population,the mean number of obesity-related cardiovascular risk factors(hypertension,low high-density lipoprotein cholesterolemia and/or hypertriglyceridemia,and hyperglycemia)was greater than 1.0 at 100 cm2 of VFA,irrespective of gender,age and body mass index.Our group also demonstrated that reduction of visceral fat accumulation subsequent to voluntary lifestyle modification,"Hokenshido",correlated with a decrease in the number of obesity-related cardiovascular risk factors.It is important to select the most appropriate subjects from the general population(e.g.,non-obese subjects with a cluster of risk factors for the metabolic syndrome)that are most suitable for body weight reduction,with the goal of preventing atherosclerotic cardiovascular diseases.
基金Supported by A grant from Foundation for Promotion of Cancer Research in Japan
文摘AIM:To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model,and to determine the con-tribution of adiponectin defi ciency to colorectal cancer development and proliferation.METHODS:We examined the influence of adiponectin defi ciency on colorectal carcinogenesis induced by the administration of azoxymethane(AOM)(7.5 mg/kg,in-traperitoneal injection once a week for 8 wk),by using adiponectin-knockout(KO) mice.RESULTS:At 53 wk after the fi rst AOM treatment,KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type(WT) mice,although the tumor incidence was not different between WT and KO mice.KO mice showed increased cell proliferation of colorec-tal tumor cells,which correlated with the expression levels of cyclooxygenase-2(COX-2) in the colorectal tumors.In addition,KO mice showed higher incidence and frequency of liver tumors after AOM treatment.Thirteen percent of WT mice developed liver tumors,and these WT mice had only a single tumor.In contrast,50% of KO mice developed liver tumors,and 58% of these KO mice had multiple tumors.CONCLUSION:Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice.This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.
文摘AIM： To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide （LPS） -induced liver injury.METHODS： D-galactosamine （GAIN） and LPS were injected intraperitoneally into adiponectin-/- mice and wild type mice. Kupffer cells, isolated from Sprague-Dawley rats, were preincubated with or without adiponectin, and then treated with LPS.RESULTS： In knockout mice, GalN/LPS injection significantly lowered the survival rate, significantly raised the plasma levels of alanine transaminase and tumor necrosis factor-α （TNF-α） and significantly reduced IL-10 levels compared with wild type mice. TNF-α gene expression in the liver was which higher and those of IL-10 were lower in knockout mice than in wild type mice. In cultured adiponectin-pre-treated Kupffer cells, LPS significantly lowered TNF-α levels and raised IL-10 levels in the culture media and their respective gene expression levels, compared with Kupffer cells without adiponectinpre-treatment.CONCLUSION： Adiponectin supresses TNF-α production and induces IL-10 production by Kupffer cells in response to LPS stimulation, and a lack of adiponectin enhances LPS-induced liver injury.
文摘The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedsidetype artificial endocrine pancreas is now available in Japan: STG-22 (Nikkiso Co. Ltd., Japan). In the insulin infusion algorithm, insulin is infused on the basis ofits proportional and derivative actions, to blood glucose concentrations with a constant time delay. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetes mellitus, but also as an elegant research tool for investigating the pathophysiology of the disease, by using the euglycemic hyperinsulinemic glucose clamp technique. The wearable type of closed-loop system has been developed recently. The breakthrough is the establishment of a needle-type glucose sensor. The development of closed-loop glycemic control systems that enable long-term physiological regulation has focused on implantable devices. Much effort has been expended to realize these devices.
