Resistin and insulin resistance in hepatocytes: Resistin disturbs glycogen metabolism at the protein level

Resistin has been considered to link obesity with type 2 diabetes. Liver glycogen metabolism plays an essential role in maintaining glucose homeostasis, we investigated the effect of resistin on liver glycogen metabolism and attempted to identify its role in initiating insulin resistance and type 2 diabetes. Primary culture of rat hepatocytes was treated by resistin and insulin. Glycogen content was determined by the anthrone-reagent method. Real-time PCR, Western blot and enzymatic activity assay were used to detect key enzymes and genes involved in glucose metabolism. Hepatocytes exposed to resistin, but only in the presence of insulin, show a decrease in insulin-stimulated glycogen content. Decreased insulin receptor expression and GS activity and elevated GP activity was observed after the treatment of hepatocytes with resistin. No significant changes in the expression of the genes for these proteins were observed. These results strongly suggest that resistin effects glycogen metabolism at the protein level, and resistin is highly associated with insulin resistance and type 2 diabetes and is a candidate for the prevention and treatment of type 2 diabetes. Our results should lead to the development of novel strategies for the treatment of type 2 diabetes.     

The Genetics of Non-insulin-dependent Diabetes Mellitus in South India: An Overview

Non-insulin-dependent diabetes mellitus affects approximately 10% of urban Indian and Indian migrant populations and as such carries major health implications for these groups. Whilst a strong genetic component to the aetiology of non-insulin-dependent diabetes mellitus is incontestable, progress in identifying the specific genetic determinants involved in its pathogenesis has been slow. In studies of South Indian pedigrees, preliminary segregation analysis indicates that non-insulin-dependent diabetes mellitus is likely to be a polygenic disease. A number of candidate genes have been studied with the aim of demonstrating either association or linkage with the disease; in South Indians the only positive results thus far have been associations between non-insuiin-dependent diabetes mellitus and the genes for insulin, apolipoprotein D and complement component C4B. However, it seems likely that these genes contribute only a small proportion of the genetic susceptibility to non-insulin-dependent diabetes mellitus in this ethnic group and that the major genes underlying glucose intolerance remain to be determined.     

Use of continuous glucose monitoring systems in children with type 1 diabetes

Continuous glucose monitoring systems (CGMS) offer a recent technological solution to fear of hypoglycemia and reduction in hyperglycemia. With glucose readings every 5 minutes, and the alarm capabilities to signal rapid increases or decreases in blood glucose, they afford a sense of security for both children and parents. Although children and parents must continue to be vigilant in the treatment of diabetes, CGMS may effectively allow tight diabetes control with earlier detection of hypoglycemia onset. This article provides an overview of CGMS available at the time of publication; new generations of systems have been introduced annually with improvements in sensitivity and user friendliness.     

Lipocalin-2 as a biomarker for diabetic nephropathy

Diabetes is a major global public health issue. The prevalence of type 1 diabetes is comparatively static, as hereditary and genetic causes are involved, while type 2 diabetes (T2D) prevalence is increasing day by day. T2D is associated with chronic complications, including diabetic neuropathy (DN), nephropathy, retinopathy, and other complications like diabetic foot. DN is the main complication of both types of diabetes. DN can be diagnosed by routine laboratory tests, microalbuminuria > 300 mg/24 h, and a gradual decrease in glomerular filtration rate. As the appearance of microalbuminuria is a late manifestation, an early marker for renal damage is needed. Lipocalin-2, also known as neutrophil gelatinase-associated lipocalin (NGAL), is a small protein purified from neutrophil granules and a good marker for kidney disease. NGAL is a transporter protein responsible for many physiological processes, such as inflammation, generation of the immune response, and metabolic homeostasis. NGAL has been reported to depict the early changes in renal damage when urine microalbumin is still undetecable. Therefore, elucidating the role of NGAL in detecting DN and understanding its mechanism can help establish it as a potential early marker for DN.     

Genetic prediction of atherosclerosis: lessons from studies in native Canadian populations.

The Oji-Cree from Northern Ontario have a very high prevalence of cardiovascular disease and diabetes mellitus, whereas the Inuit from Nunavut have a very low prevalence of these diseases. There are significant differences between Oji-Cree, Inuit and white subjects with respect to the frequencies of putative 'deleterious alleles' of several candidate genes in diabetes and atherosclerosis. Specifically, compared to whites, both Oji-Cree and Inuit have an excess of 'deleterious alleles' from 12 candidate genes in atherosclerosis and/or diabetes. However, it would appear that these differences in genetic architecture are not sufficient to account for the wide disparity in disease prevalence between the two aboriginal groups. It is very likely that environmental lifestyle factors, such as maintenance of a traditional diet and an increased level of activity, can override an apparent background of genetic susceptibility to these diseases in native people. Full understanding of the genetic component will require more effort because of confounding factors such as small genetic effects, non-mendelian inheritance, gene-gene interactions and gene-environment interactions. However, even before there is a full understanding of the identity of the all the genes involved, and of how their products might contribute to disease susceptibility in an individual or a community, there would be some justification to recommend an intervention strategy at this point in time. Such an intervention strategy would stress a return to a more traditional diet and lifestyle in order to avert and reverse these disease phenotypes in Canadian aboriginal communities.     

The genodermatoses: candidate diseases for gene therapy

Tremendous progress has been made in understanding the genetic basis of different forms of genodermatoses, a group of heritable diseases displaying a spectrum of phenotypic manifestations and clinical severity. The information about the underlying mutations in the candidate gene/protein systems has provided the basis for initial development of cutaneous gene therapy, and these heritable conditions appear to serve as appropriate candidate diseases for such efforts. Because of its accessibility and the fact that resident skin cells, such as epidermal keratinocytes and dermal fibroblasts, can be readily propagated in culture, skin serves as an appropriate target tissue for gene therapy. Various strategic considerations, including the use of in vivo or ex vivo approaches, gene replacement versus gene repair, utilization of different delivery systems, etc., require careful prioritization depending on the type of mutations and their pathogenetic consequences at the mRNA and protein levels.     

Gene expression analysis on the liver of cholestyramine-treated type 2 diabetic model mice

Recent experimental and clinical studies have indicated that bile acid-binding agents are effective not only for treating hypercholesterolemia, but also for type 2 diabetes. To investigate the molecular mechanism underlying the effect of cholestyramine, a bile acid-binding agent, on type 2 diabetes, we examined gene expression of the livers of cholestyramine-treated type 2 diabetic model mice. Type 2 diabetic NSY/Hos mice were fed a high fat diet supplemented with 1% (w/w) cholestyramine for 8 weeks. Cholestyramine treatment prevented the increase in body weight, plasma cholesterol, triglycerides, glucose, insulin levels, and hepatic steatosis. DNA microarray analysis was performed on the liver, which revealed that the genes related to synthesis of cholesterol and its derivatives were increased and the genes regulated by liver X receptors, such as the sterol regulatory element-binding protein 1 gene, were decreased in the group treated with cholestyramine. Expression of the genes related to carbohydrate metabolism was little changed in the cholestyramine group. Furthermore, we performed real-time RT-PCR analysis, which highly correlated with DNA microarray data (r = 0.957, P < 0.001). This study provides a valuable basis for further research on the biological functions of bile acid-binding agents in models of type 2 diabetes.     

Antidiabetic agents in patients with hepatic impairment

Chronic liver disease (CLD) often coexists with type 2 diabetes mellitus, making diabetes management a challenge to the clinician. It is well known that liver is the major site of drug metabolism, and, therefore, its impairment affects hepatic metabolism of many antidiabetic agents. Furthermore, patients with CLD have serious comorbidities such as impaired renal function, hypoalbuminemia, lactic acidosis, hypoglycemia and malnutrition, making their treatment even more difficult. On the other hand, most of the antidiabetic agents, with the exception of insulin, need dosage titration due to alterations to their pharmacokinetics in patients with CLD. For well-established antidiabetic treatments, like metformin and sulfonylureas there are studies regarding their dosage chance in these patients. However, despite the growing problem of management of diabetes in patients with CLD the existing literature data, especially on newer antidiabetic agents, are limited and, furthermore, no direct guidelines exist. Therefore, in the present review article we try to summarize the existing literature data regarding management of diabetes in patients with CLD.     

中年2型糖尿病患者认知功能探讨

目的 通过心理测验，了解中年2型糖尿病(NIDDM)患的认知功能。方法 年龄、性别、化程度相匹配的INDDM患和对照组各60名，排除可能影响认知功能的各种神经、精神疾病、药物和酒精滥用，糖尿病人需排除曾有严重低血糖发作和酮症酸中毒，做韦氏记忆量表和威斯康星卡片分类测验。结果 2型糖尿病组认知测验成绩低于对照组，有显差异。结论 中年2型糖尿病患存在着认知功能损害。     

A型行为类型糖尿病人调查及护理

对住院２５９名确诊为糖尿病患者进行了Ａ型行为类型调查。结果有１４８名属于Ａ型行为类型。对Ａ型行为糖尿病患者在住院期间针对其情绪行为及临床表现特征,采取了加强心理护理,提高患者自我护理意识以及环境、家庭等多方位护理措施,收到了良好效果。     

Treating the metabolic syndrome

The metabolic syndrome (MS), a cluster of metabolic abnormalities with insulin resistance as its central component, is increasing in prevalence and is associated with an increased risk of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Current evidence supports an aggressive intervention approach that comprises lifestyle modification in conjunction with drug treatment of the MS components. Healthier eating and regular exercise greatly reduce waistline and body mass index, lower blood pressure and improve lipid profile. Lifestyle modification has been proven to prevent T2DM development. Nevertheless, appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs. Only severely obese patients require specific drug treatments. Very often, drug combinations will be necessary to manage multiple risk factors. As we progress in the understanding of the pathophysiology of the MS, new targets for therapies will probably be identified and new treatments will prove to be even more efficacious than those currently available for the management of this life-threatening condition.     

对2型糖尿病病人实施健康教育的体会

目的 :探讨健康教育对2型糖尿病病人血糖水平影响的临床意义。方法 :对 60例 2型糖尿病住院病人随机分成A、B两组 ,A组在降糖药物治疗的同时进行健康教育。B组为对照组 ,给予降糖药物治疗及传统的护理方法。 3个月后对两组病人血糖水平进行对比观察。结果 :A、B两组病人血糖比较有统计学意义 (P <0 .0 1) ,且A组病人对糖尿病知识的掌握也有不同程度的提高。结论 :此项研究提示对糖尿病病人进行健康教育能提高病人对糖尿病的认识 ,改善不良服药依从性 ,从而对控制血糖、预防并发症具有重要意义     

The genetics of non-insulin-dependent diabetes mellitus in south India: an overview.

Non-insulin-dependent diabetes mellitus affects approximately 10% of urban Indian and Indian migrant populations and as such carries major health implications for these groups. Whilst a strong genetic component to the aetiology of non-insulin-dependent diabetes mellitus is incontestable, progress in identifying the specific genetic determinants involved in its pathogenesis has been slow. In studies of South Indian pedigrees, preliminary segregation analysis indicates that non-insulin-dependent diabetes mellitus is likely to be a polygenic disease. A number of candidate genes have been studied with the aim of demonstrating either association or linkage with the disease; in South Indians the only positive results thus far have been associations between non-insulin-dependent diabetes mellitus and the genes for insulin, apolipoprotein D and complement component C4B. However, it seems likely that these genes contribute only a small proportion of the genetic susceptibility to non-insulin-dependent diabetes mellitus in this ethnic group and that the major genes underlying glucose intolerance remain to be determined.     

Dopamine genes and migraine

Migraine is a common chronic disorder with an etiology still mostly unknown. Several neurotransmitters such as dopamine and serotonin are considered to be involved in the pathogenesis of the disease and the study of their systems is crucial in the understanding of migraine. Dopaminergic receptors are variously represented in human CNS and periphery. The hypothesis that a hypersensitivity of the dopaminergic system may have a role in migraine is based on clinical and genetic data. Genetic data are represented by association studies using dopaminergic genes as candidate genes which show that the D2 receptor gene appears to be involved in the pathogenesis of migraine.     

超声心动图评价2型糖尿病患者心脏功能研究进展

2型糖尿病发病率在我国逐年增长,其心血管疾病的发病风险高,早期发现心脏功能的异常并进行有效干预,可延缓或避免危险事件的发生。超声心动图具有简便、无创、廉价、迅速、准确等优点,可为糖尿病的诊断及制定治疗方案提供可靠依据。本文就组织多普勒成像、分层应变成像、超声血流向量成像、二维斑点追踪、实时三维超声成像、三维斑点追踪等技术在2型糖尿病心脏功能中的应用进行综述。     

Diabetes mellitus: An overview of the types,prevalence, comorbidity,complication, genetics,economic implication,and treatment

Diabetes is one of the deadliest diseases. Due to its effects on the lives of people, it has attracted a lot of attention recently. The causes of the various forms of diabetes, including type 1 and type 2, were discussed along with how they affect those who have the disease. Younger people are more prone to type 1 diabetes than older people, who are more likely to develop type 2. The treatment options and strategies for the two forms of diabetes were also discussed in addition to how the disease affects the quality of life of people. Among several factors that were explained, it has been shown that people from low and middle-income countries are more prone to having diabetes. Additionally, the condition is more likely to affect some races more than others. It is associated with obesity. According to statistics, those who are poor are more severely affected by the disease. The progression of the disease over time has been associated with an increase in disability and mortality.     

Candidate gene studies of bipolar disorder

Genetic factors undoubtedly play an important role in determining vulnerability to bipolar disorder but the task of finding susceptibility genes is not trivial. Candidate gene studies, usually employing the association approach, offer the potential to discover the genes of relatively modest effect size that are expected for a complex genetic disorder. Candidate gene approaches depend crucially on our current understanding of disease pathophysiology, and attention has consequently been focussed on a limited range of neurotransmitter systems implicated by the action of drug treatments. Despite no unequivocal, consistently replicated findings, a number of intriguing results have emerged in the literature, both for bipolar disorder in general and for subtypes such as bipolar affective puerperal psychosis and rapid cycling bipolar illness. Genes of particular current interest include those encoding the serotonin transporter, monoamine oxidase A (MAOA) and catechol-O-methyl transferase (COMT). As susceptibility genes are found and knowledge of aetiology advanced it is likely that many more candidate genes in novel biological systems will attract attention.     

Nutritional deficiencies in the pediatric age group in a multicultural developed country,Israel

Nutrient deficiencies are prevalent worldwide. Diseases and morbid conditions have been described to result from nutritional deficiencies. It is essential to address nutrient deficiencies as these may lead to chronic long-term health problems such as rickets, iron deficiency anemia, goiter, obesity, coronary heart disease, type 2 diabetes, stroke, cancer and osteoporosis. In the present review we surveyed the extent and severity of nutritional deficiencies in Israel through a selective and comprehensive Medline review of previous reports and studies performed during the last 40 years. Israeli populations have multiple nutritional deficiencies, including iron, calcium, zinc, folic acid, and vitamins B12, C, D and E, spanning all age groups, several minorities, and specific regions. In Israel, some of the nutrients are mandatorily implemented and many of them are implemented voluntarily by local industries. We suggest ways to prevent and treat the nutritional deficiencies, as a step to promote food fortification in Israel.     

Mutations in the genes for hepatocyte nuclear factor (HNF)-1alpha, -4alpha, -1beta, and -3beta; the dimerization cofactor of HNF-1; and insulin promoter factor 1 are not common causes of early-onset type 2 diabetes in Pima Indians

OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of type 2 diabetes characterized by an early age at onset and autosomal dominant inheritance. MODY can result from heterozygous mutations in at least five genes. The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contribute to the development of early-onset type 2 diabetes in Pima Indians. RESEARCH DESIGN AND METHODS: The coding regions of the known MODY genes hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, HNF-1beta, and insulin promoter factor 1 and the coding regions of two MODY candidate genes, HNF-3beta and the dimerization cofactor of HNF-1, were sequenced in genomic DNA from Pima Indians. The primary "affected" study population consisted of 46 Pima Indians whose age at onset of type 2 diabetes was < or =20 years. DNA sequence variants identified in the affected group were then analyzed in a group of 80 "unaffected" Pima Indians who were at least 40 years old and had normal glucose tolerance. RESULTS: A total of 11 polymorphisms were detected in these genes. However, none of the polymorphisms differed in frequency among Pima Indians with an early age at onset of diabetes compared with older Pima Indians with normal glucose tolerance. CONCLUSIONS: Mutations in these known MODY or MODY candidate genes are not a common cause of early-onset diabetes in Pima Indians.