ISRN endocrinology最新文献

The prevalence of obesity, which is a heritable trait that arises from the interactions of multiple genes and lifestyle factors, continues to increase worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past several years, various genetic epidemiological approaches have been utilized to identify genetic loci for obesity. Recent evidence suggests that development of obesity involves hormones and neurotransmitters (such as leptin, cocaine- and amphetamine-regulated transcript (CART), and ghrelin) that regulate appetite and energy expenditure. These hormones act on specific centers in the brain that regulate the sensations of satiety. Mutations in these hormones or their receptors can lead to obesity. Aberrant circadian rhythms and biochemical pathways in peripheral organs or tissues have also been implicated in the pathology of obesity. More interestingly, increasing evidence indicates a potential relation between obesity and central nervous system disorders (such as cognitive deficits). This paper discusses recent advances in the field of genetics of obesity with an emphasis on several established loci that influence obesity. These recently identified loci may hold the promise to substantially improve our insights into the pathophysiology of obesity and open up new therapeutic strategies to combat growing obesity epidemic facing the human population today.

Reduced expression of GATA4, a transcriptional factor for structural and cardioprotective genes, has been proposed as a factor contributing to the development of cardiomyopathy. We investigated whether the reduction of cardiac GATA4 expression reported in diabetes alters the expression of downstream genes, namely, atrial natriuretic peptide (ANP), B-type natriuretic, peptide (BNP), and α- and β-myosin heavy chain (MHC). db/db mice, a model of type 2 diabetes, with lean littermates serving as controls, were studied. db/db mice exhibited obesity, hyperglycemia, and reduced protein expression of cardiac GLUT4 and IRAP (insulin-regulated aminopeptidase), the structural protein cosecreted with GLUT4. Hearts from db/db mice had reduced protein expression of GATA4 (~35%) with accompanying reductions in mRNA expression of ANP (~40%), BNP (~85%), and α-MHC mRNA (~50%) whereas expression of β-MHC mRNA was increased by ~60%. Low GATA4 was not explained by an increased ligase or atrogin1 expression. CHIP protein content was modestly downregulated (27%) in db/db mice whereas mRNA and protein expression of the CHIP cochaperone HSP70 was significantly decreased in db/db hearts. Our results indicate that low GATA4 in db/db mouse heart is accompanied by reduced expression of GATA4-regulated cardioprotective and structural genes, which may explain the development of cardiomyopathy in diabetes.

Objective. To investigate the possible association of calcium and vitamin D deficiency with hypoadiponectinemia in women with PCOS. Subjects and Methods. In this case-control study, 103 PCOS cases and 103 controls included. The concentrations of calcium, 25-OH-vitamin D (25OHD), adiponectin, insulin, glucose, total cholesterol, HDL-cholesterol, triglyceride (TG), and androgens were measured in fasting blood samples. Results. Adiponectin (8.4 ± 2.7 ng/mL versus 13.6 ± 5 ng/mL in control group, P : 0.00), calcium (2 ± 0.1 mmol/L versus 2.55 ± 0.17 mmol/L in controls, P : 0.00), and 25-OH-Vit D (30 ± 2.99 nmol/L versus 43.7 ± 5.2 nmol/L in control group, P : 0.00) levels were decreased in women with PCOS. Subjects with PCOS had higher concentrations of TG (1.4 ± 0.77 mmol/L versus 1.18 ± 0.75 mmol/L in control group, P : 0.019) and dehydroepiandrosterone sulfate (DHEA-S) (10.7 ± 11 mmol/L versus 9.7 ± 10.4, P : 0.02 in control group). There were significant correlations between adiponectin concentrations with calcium (r : 0.78, P : 0.00) and 25OHD levels (r : 0.82, P : 0.00). The association of hypoadiponectinemia and PCOS was not significant considering 25OHD as a confounding factor. Conclusion. The present findings indicate that the association of hypoadiponectinemia with PCOS is dependent on vitamin D. A possible beneficiary effect of vitamin D on the metabolic parameters in PCOS may be suggested.

Type 2 Diabetes Mellitus (T2DM) is characterized by chronic hyperglycemia with disturbance in carbohydrate, lipid, and protein metabolism due to insulin resistance and beta cell dysfunction. Epidemiological studies have confirmed a global pandemic of T2DM, which has created an enormous burden on society, with regard to morbidity, mortality, and health care expenditures. Life style modifications are fundamental not only in early stages of disease management but need to be intensified as disease progresses. United Kingdom Prospective Diabetes Study (UKPDS) has demonstrated the progressive nature of T2DM, and as disease progresses, a combination agents-oral antidiabetic drugs (OAD) and insulin-are needed in order to maintain good sugar control. The general consensus of HbA1c target for most patients is less than 7%, and various guidelines and algorithms have provided guidance in patient management to keep patient at goal. As our understanding of pathophysiological defects advances, targeting treatment at underlying defects not only enables us to achieve HbA1c goal but also reduces morbidities, mortalities, and progression of the disease. Traditional oral agents like metformin and sulfonylureas have failed to arrest the progression of T2DM. New agents such as TZD, DPP-4 inhibitor, and SGLT-2 may increase our armamentariums against T2DM.

High-fat programming, by exposure to a high-saturated-fat diet in utero and/or during lactation, compromises beta-cell development and function in neonatal and weanling offspring. Therefore, high-fat programming effects were investigated on metabolism and islet architecture in young adult rats. Three-month-old male and female Wistar rat offspring were studied: HFG (maintained on a high-fat diet throughout fetal life), HFP (high-fat diet maintenance from birth to 3 months), and HFGP (high-fat diet maintenance throughout fetal and postnatal life). Control rats were maintained on a standard laboratory diet. Pancreata were double immunolabeled for insulin and glucagon to assess islet morphology and with Ki-67 to determine islet and acinar cell proliferation. HFP and HFGP males were heavier, hyperleptinemic, and hyperinsulinemic. Hyperglycemia presented in HFP males, HFP females, and HFGP males. HFGP males and HFP females were insulin resistant. HFP males displayed beta- and alpha-cell hyperplasia with alpha-cell hypertrophy evident in HFP females. Acinar cell proliferation rates were increased in HFP males. Postnatal high-fat programming induced the most diabetogenic phenotype with high-fat maintenance throughout fetal and postnatal life resulting in a severely obese phenotype. Fetal and postnatal nutrition shapes offspring health outcomes.

Genetic susceptibility plays a key role in type 1 diabetes development. Because miR-541 gene was located within the associated chromosome loci and its target genes include the diabetes-associated gene neurogenin3, this study aimed to investigate whether miR-541 had type 1 diabetes-associated genetic variations. Type 1 diabetes children and healthy volunteers were recruited; direct sequencing was performed in initial 69 patients and 46 volunteers. We identified 1 reported SNP (rs12893725) and 3 novel genetic variations, for the candidate -404 G→T variation, restriction fragment length polymorphism (RFLP) was performed in total 247 diabetes children and 212 healthy volunteers, a different distribution trait of allele frequencies was found between the two groups, and further clinical analysis found no significant correlation between clinical parameter and genotypes among patients. In addition, by luciferase reporter assay, -404 was found to be within putative promoter region of pre-miR-541; although mutation of G→T has no effect on promoter activity, a significant secondary structure alteration may possibly influence its processing and transcription. In conclusion, we identified 3 novel genetic variations in putative promoter of miR-541 in type 1 diabetes patients; -404 G→T of miR-541 is a potential T1D-associated genetic variation.

The pancreas is composed of two compartments that deliver digestive enzymes and endocrine hormones to control the blood sugar level. The endocrine pancreas consists of functional units organized into cell clusters called islets of Langerhans where insulin-producing cells are found in the core and surrounded by glucagon-, somatostatin-, pancreatic polypeptide-, and ghrelin-producing cells. Diabetes is a devastating disease provoked by the depletion or malfunction of insulin-producing beta-cells in the endocrine pancreas. The side effects of diabetes are multiple, including cardiovascular, neuropathological, and kidney diseases. The analyses of transgenic and knockout mice gave major insights into the molecular mechanisms controlling endocrine pancreas genesis. Moreover, the study of animal models of pancreas injury revealed that the pancreas has the propensity to undergo regeneration and opened new avenues to develop novel therapeutic approaches for the treatment of diabetes. Thus, beside self-replication of preexisting insulin-producing cells, several potential cell sources in the adult pancreas were suggested to contribute to beta-cell regeneration, including acinar, intraislet, and duct epithelia. However, regeneration in the adult endocrine pancreas is still under controversial debate.

Background. Chronic autoimmune thyroiditis (CAT) frequently alters thyroid vascularization, likely as a result of the autoimmune process. Objective. To evaluate the effects of low-level laser therapy (LLLT) on the thyroid vascularization of patients with hypothyroidism induced by CAT using color Doppler ultrasound parameters. Methods. In this randomized clinical trial, 43 patients who underwent levothyroxine replacement for CAT-induced hypothyroidism were randomly assigned to receive either 10 sessions of LLLT (L group, n = 23) or 10 sessions of a placebo treatment (P group, n = 20). Color Doppler ultrasounds were performed before and 30 days after interventions. To verify the vascularity of the thyroid parenchyma, power Doppler was performed. The systolic peak velocity (SPV) and resistance index (RI) in the superior (STA) and inferior thyroid arteries (ITAs) were measured by pulsed Doppler. Results. The frequency of normal vascularization of the thyroid lobes observed in the postintervention power Doppler examination was significantly higher in the L than in the P group (P = 0.023). The pulsed Doppler examination revealed an increase in the SPV of the ITA in the L group compared with the P group (P = 0.016). No significant differences in the SPV of the STA and in the RI were found between the groups. Conclusion. These results suggest that LLLT can ameliorate thyroid parenchyma vascularization and increase the SPV of the ITA of patients with hypothyroidism caused by CAT.

Despite the availability of many other agents, insulin is widely used as a treatment for type 2 diabetes. In vitro, insulin stimulates the growth of cancer cells, through the interaction with insulin-like growth factor-1 (IGF-1) receptors and its own receptors. In observational surveys on type 2 diabetes, insulin therapy is associated with an increased incidence of several forms of cancer, although it is difficult to discriminate the effect of confounders from that of insulin itself. Randomized trials do not confirm the increased risk associated with insulin therapy, although they do not allow to rule out some negative effects on specific forms of cancer, at least at higher doses. Among insulin analogues, glargine has a higher affinity for the IGF-1 receptor and a greater mitogenic potency in vitro than human insulin, but it is extensively metabolized in vitro to products with low IGF-1 receptor affinity. Overall, epidemiological studies suggest a possible increase of risk with glargine, with respect to human insulin, only at high doses and for some forms of cancer (i.e., breast). Data from clinical trials do not confirm, but are still insufficient to totally exclude, such increased risk. However, beneficial effects of insulin outweigh potential cancer risks.

Purpose. Measurement of serum calcitonin is important in the followup of patients with medullary thyroid carcinoma (MTC) and reliably reflects the presence of the disease. This is the largest study so far in bibliography investigating the diagnostic accuracy of combined [(18)F]FDG-PET/CT in patients with MTC and elevated calcitonin levels. Methods. Between February 2007 and February 2011, 59 [(18)F]FDG-PET/CT were performed on 51 patients with MTC and elevated calcitonin levels for localization of recurrent disease. Conventional morphologic imaging methods were negative or showed equivocal findings. Results. Among the 59 [(18)F]FDG-PET/CT, 29 were positive (26 had true-positive and 3 false-positive findings) and 30 negative. The overall per-patient sensitivity of [(18)F]FDG-PET/CT was 44.1%. Using as cut-off point the calcitonin value of 1000 pg/ml, in patients with calcitonin exceeding this value, sensitivity raised to 86.7%. The overall sensitivity of [(18)F]FDG-PET/CT was lower (23%) in patients with MEN IIA syndrome. Conclusion. The findings of this paper show that [(18)F]FDG-PET/CT is valuable for the detection of recurrence in patients with highly elevated calcitonin levels, >1000 pg/mL, but in patients with lower calcitonin levels, its contribution is questionable. Also, there is evidence that the sensitivity of [(18)F]FDG-PET/CT is lower in patients with MTC as part of MEN IIA syndrome.