RSSInsulin Sensitivity After Maximal and Endurance Resistance Training.
Source
1Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; 2Faculty of Education, Nord-Trøndelag University College, Levanger, Norway; 3Department of Health Science, Nord-Trøndelag University College, Levanger, Norway; 4Department of Health Sciences, Mid Sweden University, Östersund, Sweden; and 5Hormone Laboratory, Oslo University Hospital-Aker, Oslo, Norway.
Abstract
Hansen, E, Landstad, BJ, Gundersen, KT, Torjesen, PA, and Svebak, S. Insulin sensitivity after maximal and endurance resistance training. J Strength Cond Res 26(2): 327-334, 2012-The purpose of the study was to compare the effects of maximal resistance training (MRT) vs. endurance resistance training (ERT) on improvements in insulin levels and glucose tolerance in overweight individuals at risk of developing type 2 diabetes. Eighteen participants with baseline values suggesting impaired glucose tolerance were randomly assigned to 1 of 2 groups. Group 1 engaged in supervised MRT (Bernstein inverted pyramid system: 5 × 3-4, 60-85% 1 repetition maximum [1RM]), 3 d·wk over 4 months, whereas members of group 2 acted as controls. Later, group 2 engaged in supervised ERT (3 × 12-15, 45-65% 1RM), 3 d·wk over a 4 month period with the 2 prebaselines as controls. Both interventions consisted of 8 exercises that included the entire body. Glucose (fasting and 2-hour test), insulin and C-peptide measures were assessed from pre to post in both groups. The MRT led to reduced blood levels of 2-hour glucose (p = 0.044) and fasting C-peptide (p = 0.023) and decreased insulin resistance (p = 0.040). The ERT caused a significant reduction in the blood levels of insulin (p = 0.023) and concomitant positive effects on % insulin sensitivity (p = 0.054) and beta-cell function (p = 0.020). The findings indicate that both MRT and ERT lead to decreased insulin resistance in people with a risk of developing type 2 diabetes; MRT led to a greater increase in glucose uptake capacity (in muscles), whereas ERT led to greater insulin sensitivity, supporting the recommendation of both MRT and ERT as primary intervention approaches for individuals at a risk of developing type 2 diabetes.
- PMID:
- 22240549
- [PubMed - as supplied by publisher]
Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells.
Abstract
ABSTRACT:
BACKGROUND:
Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D). Evidence that human cord blood-derived multipotent stem cells (CB-SCs) can control autoimmune responses by altering regulatory T cells (Tregs) and human islet beta cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D.
METHODS:
We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separate lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n = 15) with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range, 15 to 41), and median diabetic history was 8 years (range, 1 to 21).
RESULTS:
Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C) values, and decrease the median daily dose of insulin in patients with some residual beta cell function (n = 6) and patients with no residual pancreatic islet beta cell function (n = 6). Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3) did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of costimulating molecules (specifically, CD28 and ICOS), increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance.
CONCLUSIONS:
Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell Educator therapy reverses autoimmunity and promotes regeneration of islet beta cells. Successful immune modulation by CB-SCs and the resulting clinical improvement in patient status may have important implications for other autoimmune and inflammation-related diseases without the safety and ethical concerns associated with conventional stem cell-based approaches. Trial registration: ClinicalTrials.gov number, NCT01350219.
Long-Term Pancreatic Allograft Survival After Renal Retransplantation in Prior Simultaneous Pancreas-Kidney Recipients.
Source
Division of Transplantation, University of Maryland School of Medicine, University of Maryland, Baltimore, MD Division of Transplantation, University of Wisconsin, Madison, WI Division of Transplantation, Pritzker School of Medicine, Chicago, IL.
Abstract
Over a 23-year period, our center performed 82 renal retransplants in prior simultaneous pancreas-kidney recipients with functioning pancreatic allografts. All patients were insulin-independent at retransplantation. We aimed to quantify the risk of returning to insulin therapy and to identify factors that predispose patients to pancreatic allograft failure after renal retransplantation. Among these 82 patients, pancreatic allograft survival after renal retransplantation was 78%, 49% and 40% at 1, 5 and 10 years. When analyzing risk factors, we unexpectedly found no clear relationship between the cause of primary renal allograft failure, hemoglobin A1c (HbA1c) or fasting C-peptide level at retransplant and subsequent pancreatic allograft failure. An elevated HbA1c in the month after renal retransplant correlated with subsequent pancreatic graft loss and patients experiencing pancreatic graft loss were more likely to subsequently lose their renal retransplant. Although it is difficult to prospectively identify those patients who will return to insulin therapy after repeat renal transplantation, the relatively high frequency of this event mandates that this risk be conveyed to patients. Nonetheless, the survival benefit associated with renal retransplantation justifies pursuing retransplantation in this population.
© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
C-peptide and its correlation to parameters of insulin resistance in the metabolic syndrome.
Source
King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia. ma.kamal@live.com.
Abstract
The progress of metabolic syndrome (MetS) continues with the onset of type-2 diabetes mellitus (Type-2 DM) along with linkage to other disorders such as neurodegenerative, especially Alzheimer's disease (AD), via oxidative stress and low grade systemic inflammatory process. Type-2 DM and AD are health disorders of priority research. The treatment for an individual suffering with Type-2 DM and/or AD requires monitoring by clinicians. The aim of this study was to investigate the role of C-peptide and its correlation to insulin resistance, body mass index (BMI), β cell function, insulin sensitivity, lipid profile and hemoglobin A1c (HbA1c). The study was designed to include 96 Type-2 DM individuals from India. 58.3% males and 41.7% females were selected and fasting blood samples were collected for estimation of fasting C-peptide, fasting blood sugar (FBS), postprandial blood sugar (PPBS), HbA1c and lipid profile. Analysis was done on Hitachi912 and Elecsys 2010 using Roche reagents and standard controls. Anthropometries to calculate BMI and β cell function, insulin sensitivity, and insulin resistance were obtained. The statistical tool ANOVA, followed by calculation of p-value and r-value were applied for investigating correlation of C-peptide levels to those of high density lipoprotein-C (HDL-C), low density lipoprotein-C (LDL-C), triglycerides (TGL), HbA1c, β cell function, insulin sensitivity and insulin resistance. Highly significant positive correlations were observed in different quantiles of C-peptide levels to the studied parameters of MetS, BMI and % β cell function. Lower HDL-C level was found to be significantly related to higher C-peptide levels. Similarly, TGL and C-peptide levels displayed a significant positive correlation. A significant negative correlation was observed between C-peptide quantiles and % sensitivity. Thus, insulin resistance showed a positive correlation until the fourth quantile. No significant correlation was observed between C-peptide and HbA1c levels. This study demonstrates that assessment of C-peptide levels is a useful tool to monitor the progress of MetS among patients suffering from Type-2 DM and AD, as these disorders are intertwined to each other by common metabolic pathways. Assessment of C-peptide levels, along with HDL-C levels, in patients can be used to monitor insulin resistance.
- PMID:
- 22229322
- [PubMed - as supplied by publisher]
Clinical, biochemical, and immunological characteristics of newly diagnosed nonobese diabetic patients aged 18-45 years in China.
Abstract
BACKGROUND:
The purpose was to characterize the clinical, biochemical, and immunological features of newly diagnosed adult-onset nonobese diabetic patients in China.
METHODS:
Newly diagnosed diabetic patients aged 18-45 years with body mass index<23 kg/m(2) were included. Excluding one mitochondrial diabetes patient, there were 102 diabetic patients enrolled in this study. Clinical and biochemical data were collected and analyzed. Radioimmunoassay was used to detect islet autoantibodies.
RESULTS:
Among the 102 study participants, 68.6% had type 1 diabetes (T1DM), 20.6% had type 2 diabetes (T2DM), and 10.8% had latent autoimmune diabetes in adults (LADA). About 92% of the T1DM patients presented hyperglycemic symptoms. The corresponding number in T2DM and LADA patients was 13% and 38%, respectively (P<.01). C-peptide in T2DM patients (1.4±0.7 ng/ml) was significantly higher than that in T1DM (0.4±0.3 ng/ml) and LADA (0.4±0.2 ng/ml) patients (P<.01). The prevalence of glutamic acid decarboxylase antibody (GADA) (64.3%) in T1DM patients was higher than that of insulin autoantibody (17.1%) (P<.05). GADA and islet cell antibody (ICA) combination was positive in 75.7% of T1DM patients.
CONCLUSION:
T1DM patients accounted for majority of the study sample. In addition, the clinical symptoms of T1DM patients were more severe compared with T2DM patients. GADA is the most sensitive autoantibody marker for adult-onset T1DM and LADA. GADA and ICA are the best test combination for adult-onset autoimmune diabetes. Specific types of diabetes should be in mind when diabetes presents itself with special transmission mode or with other extrapancreatic manifestations.
Copyright © 2012 Elsevier Inc. All rights reserved.
A spectrum of dynamic insulin sensitivity test protocols.
Source
Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand.
Abstract
Background: Numerous tests have been developed to estimate insulin sensitivity (SI). However, most of the established tests are either too expensive for widespread application or do not yield reliable results. The dynamic insulin sensitivity and secretion test (DISST) uses assays of glucose, insulin, and C-peptide from nine samples to quantify SI and endogenous insulin secretion (UN) at a comparatively low cost. The quick dynamic insulin sensitivity test has shown that the DISST SI values are robust to significant assay omissions. Methods: Eight DISST-based variations of the nine-sample assay regimen are proposed to investigate the effects of assay omission within the DISST-based framework. SI and UN were identified using the fully-sampled DISST and data from 218 nine-sample tests undertaken in 74 female individuals with elevated diabetes risk. This same data was then used with appropriate assay omissions to identify SI and UN with the eight DISST-based assay variations. Results: Median intraprocedure proportional difference between SI values from fully-sampled DISST and the DISST-based variants was in the range of -17.9 to 7.8%. Correlations were in the range of r = 0.71 to 0.92 with the highest correlations between variants with the greatest commonality with the nine-sample DISST. Metrics of UN correlated relatively well between tests when C-peptide was assayed (r = 0.72 to 1) but were sometimes not well estimated when samples were not assayed for C-peptide (r = -0.14 to 0.75). Conclusions: The DISST-based spectrum offers a series of tests with very distinct compromises of information yield, accuracy, assay cost, and clinical intensity. Thus, the spectrum of tests has the potential to enable researchers to better allocate funds by selecting an optimal test configuration for their particular application.
© 2011 Diabetes Technology Society.
Effect of exposure to non-esterified fatty acid on progressive deterioration of insulin secretion in patients with Type 2 diabetes: a long-term follow-up study.
Source
Department of Clinical Laboratory Medicine, Wakayama Medical University, Wakayama, Japan.
Abstract
Aim: The aim of the study was to determine whether fasting serum non-esterified fatty acid (NEFA) could be associated with long-term progressive deterioration of insulin secretion in patients with Type 2 diabetes. Methods: Seventy-seven Japanese patients with Type 2 diabetes (mean BMI 23.3 kg/m(2) ) were followed for 10 years. We measured fasting C-peptide level every 1-2 years. By using the slope of regression line between fasting C-peptide level and duration, we calculated its individual annual decline as an index of insulin secretion. During the follow-up periods ofC-peptide, the patients were evaluated for fasting serum non-esterified fatty acid, LDL cholesterol, HDL cholesterol and HbA(1c) levels for the last 8 years. We excluded patients who had renal dysfunction or anti-insulin antibodies from among the insulin-treated patients. Association between the individual annual decline of fasting C-peptide level and related factors were evaluated. Results: The mean individual annual decline of fasting serum C-peptide level was -0.013 ± 0.027 nmol/l/year. Fasting serum non-esterified fatty acid level had no significant difference between the first and the last 2 years of the 8-year observation period of non-esterified fatty acid. Using multiple regression analysis, mean fasting serum non-esterified fatty acid level was associated with the individual annual decline of fasting serum C-peptide level (standardized regression coefficient -0.358, P = 0.0056), although other related factors, including HbA(1c) level, were not associated. Conclusions: Mean fasting serum non-esterified fatty acid level during an 8-year observation was independently associated with long-term progressive deterioration of insulin secretion in Japanese patients with Type 2 diabetes. © 2011 The Authors. Diabetic Medicine© 2011 Diabetes UK.
© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.
Low expression and secretion of circulating soluble CTLA-4 in peripheral blood mononuclear cells and sera from type 1 diabetic children.
Source
Division of Paediatrics & Diabetes Research Centre, Department of Molecular & Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. anna.ryden@liu.se.
Abstract
BACKGROUND:
High levels of soluble cytotoxic T-lymphocyte antigen 4 (soluble CTLA-4), an alternative splice form of the regulatory T-cell (Treg) associated CTLA-4 gene, have been associated with type 1 diabetes (T1D) and other autoimmune diseases, such as Grave's disease and myasthenia gravis. At the same time, studies have shown soluble CTLA-4 to inhibit T-cell activation through B7 binding. This study aimed to investigate the role of soluble CTLA-4 in relation to full-length CTLA-4 and other Treg-associated markers in T1D children and in individuals with high or low risk of developing the disease.
METHODS:
T1D children were studied at 4 days, 1 and 2 years after diagnosis in comparison to individuals with high or low risk of developing the disease. Isolated peripheral blood mononuclear cells were stimulated with the T1D-associated glutamic acid decarboxylase 65 and phytohaemagglutinin. Subsequently, soluble CTLA-4, full-length CTLA-4, FOXP3 and TGF-β mRNA transcription were quantified and protein concentrations of soluble CTLA-4 were measured in culture supernatant and sera.
RESULTS AND CONCLUSIONS:
Low protein concentrations of circulating soluble CTLA-4 and a positive correlation between soluble CTLA-4 mRNA and protein were seen in T1D, in parallel with a negative correlation in healthy subjects. Further, low levels of mitogen-induced soluble CTLA-4 were accompanied by low C-peptide levels. Interestingly, low mitogen-induced soluble CTLA-4 mRNA and low TGF-β mRNA expression were seen in high risk individuals, suggesting an alteration in activation and down-regulating immune mechanisms during the pre-diabetic phase. Copyright © 2011 John Wiley & Sons, Ltd.
Copyright © 2011 John Wiley & Sons, Ltd.
Interactions between Plasma Levels of 25-Hydroxyvitamin D, Insulin-Like Growth Factor (IGF)-1 and C-Peptide with Risk of Colorectal Cancer.
Source
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Abstract
BACKGROUND:
Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide have been implicated in colorectal carcinogenesis. However, in contrast to vitamin D IGF-1 is not an easily modifiable risk factor.
METHODS:
Combining data from the Health Professionals Follow up Study (HPFS) and the Nurses' Health Study cohort (NHS) additive and multiplicative interactions were examined between plasma 25-hydroxyvitamin D (25(OH)D) and IGF-1, IGFBP-3 as well as C-peptide levels in 499 cases and 992 matched controls. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively.
RESULTS:
Compared to participants with high 25(OH)D and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF-1/IGFBP-3 ratio were at elevated risk of colorectal cancer when 25(OH)D was low (odds ratio (OR): 2.05 (95% CI: 1.43 to 2.92), but not when 25(OH)D was high (OR:1.20 (95% CI: 0.84 to 1.71, p(interaction): additive = 0.06, multiplicative = 0.25). Similarly, compared to participants with high 25(OH)D and low molar IGF-1/IGFBP-3 ratio and lowC-peptide levels (reference group), participants with a combination of either high IGF-1/IGFBP-3 ratio or high C-peptidewere at elevated risk for colorectal cancer when 25(OH)D was low (OR = 1.90, 95% CI: 1.22 to 2.94) but not when 25(OH)D was high (OR = 1.15, 95% CI: 0.74 to 1.77, p(interaction): additive = 0.004; multiplicative = 0.04).
CONCLUSION:
The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP-3 ratio or C-peptide levels.
Slowly progressive insulin-dependent diabetes in a patient with primary biliary cirrhosis with portal hypertension-type progression.
Source
Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Japan.
Abstract
A 73-year-old woman had previously been diagnosed with CREST syndrome, PBC and diabetes. Hepatic fibrosis was not evident, in spite of the transudative ascites and active esophageal varices. ACA were positive, whereas AMA and anti-gp210 antibodies were negative. She showed low urinary excretion of C-peptide and was weakly positive for anti-GAD antibody. She was diagnosed with a form of PBC that progresses via portal hypertension rather than liver failure and with SPIDDM. Her HLA type did not contain risk allele for IDDM or PBC. SPIDDM should be considered when patients with PBC with portal hypertension-type progression develop diabetes.
Comparison between serum insulin levels and its resistance with biochemical, clinical and anthropometric parameters in South Indian children and adolescents.
Abstract
There is a rising trend in the prevalence of insulin resistance among obese, overweight children and adolescents. The serum insulin and its correlation with biochemical, clinical and anthropometric parameters were evaluated in 185 children and adolescents (59 control, 52 obese, 49 overweight, 25 congenital heart disease) of age group 10-17 years. The levels of serum insulin were measured by ELISA. Serum insulin levels were found to be significantly increased in children who were obese, overweight and had congenital heart disease, than controls. Serum insulin levels positively correlated with BMI, WHR, and serum C-peptide, serum leptin, total cholesterol, triglycerides, LDL-cholesterol, systolic and diastolic blood pressure. Fasting glucose levels were found to be negatively correlated with serum insulin levels. HDL-cholesterol levels were non-significant among the study groups. We identified nine obese children (five girls and four boys) with the features of metabolic syndrome and 69% of obese and overweight children were identified with insulin resistance. Insulin resistance was strongly associated with metabolic syndrome and its components, especially with central obesity and hypertriglyceridemia.
Latent Autoimmune Diabetes of Adults Is Phenotypically Similar to Type 1 Diabetes in a Minority Population.
Source
Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California-Los Angeles Medical Center, Torrance, California 90509.
Abstract
Context:Latent autoimmune diabetes of adults (LADA) is a form of autoimmune diabetes that has been classified as part of type 1 diabetes or as a distinct clinical entity. Its precise place as a disease category is therefore controversial.Objective:The objective of this study was to further examine this issue by comparing the phenotypes of LADA and type 1 diabetes in a predominately minority population.Patients and Methods:We studied 126 subjects who were anti-glutamic acid decarboxylase antibody-positive in two separate studies-63 subjects in an outpatient study (study 1), and 63 inpatients after resolution of ketoacidosis (study 2). Clinical and biochemical phenotyping was performed in all patients in each group.Results:Few significant differences were found in the clinical or biochemical phenotypes in patients classified as LADA when compared with type 1 diabetes. Adiposity, body mass index, waist/hip ratio, fasting plasma C-peptide, serum high-density lipoprotein cholesterol, and triglycerides were all similar. The only distinguishing feature was a history of hypertension (study 1) or systolic blood pressure (study 2). Also, a history of ketoacidosis did not influence the phenotype of LADA in the outpatients in any discernable way.Conclusions:We conclude that LADA and type 1 diabetes are phenotypically indistinguishable in this predominantly minority population with a mean duration of glutamic acid decarboxylase antibody-positive diabetes of about 8 yr.
[Correlations between clinical signs and hormonal parameters in young women with hirsutism].
Source
I. Javakhishvili Tbilisi State University, Department of Gynecology, Obstetrics and Reproductology, Medical faculty; I. Zhordania Institute of Human Reproduction, Tbilisi, Georgia.
Abstract
Hyperandrogenism is the pathological condition, which clinical signs are "androgendependent dermopathies" (seborrhea, acne, hirsutism, alopecia) and not in every cases evidence with hyperandrogenemia. Free testosterone is the most frequent marker of hyperandrogenism, but its determination routinely not feasible in all laboratories. Therefore, some models for calculating free and bioavailable testosterone have been developed. In women the testosterone sources are not only ovaries and adrenal glands, but also abdominal and peripheral fat. There are many investigations to definite correlations between body mass index, androgens and sex hormone binding globulin. The aim of this study was to define the correlations between clinical, biochemical markers of hyperandrogenism and body mass index, with regard of abdominal obesity in young women with hirsutism. 83 female adolescents (14-20 year) with hirsutism and 20 female adolescents in control group were included. C-peptide, estradiol, total testosterone, sex hormone binding globulin (SHBG) were measured. Free androgen index (FAI), free (cFT) and bioavailable (Bio-T) testosterone were calculated. The levels of C-peptide and glucose were used to compute Homa-IR (homeostasis model assessment for insulin resistance). There were detected significant high levels by all hormonal parameters of hyperandrogenism in women with hirsutism, than in control group. In patients with abdominal obesity were also found significant high levels by all calculated parameters of hyperandrogenism and significant low level of steroid-bind globulin, than in patients with central obesity. In two groups by hirsutism degree were not detected any differences between androgen markers. The findigs of this research suggest, that android obesity in female adolescents with hirsutism can cause harder hyperandrogenism and elevate free androgen index, free and bioavailable testosterone levels. The prophylactic reduction of body mass index may prevent complications.
- PMID:
- 22201077
- [PubMed - in process]
Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells.
Abstract
We sought to assess the potential of human cord blood-derived mesenchymal stem cells (CB-MSCs) to derive insulin-producing, glucose-responsive cells. We show here that differentiation protocols based on step-wise culture conditions initially described for human embryonic stem cells (hESCs) lead to differentiation of cord blood-derived precursors towards a pancreatic endocrine phenotype, as assessed by marker expression and in vitro glucose-regulated insulin secretion. Transplantation of these cells in immune-deficient animals shows human c-peptide production in response to a glucose challenge. This data suggests that human cord blood may be a promising source for regenerative medicine approaches for the treatment of diabetes mellitus.
Differentiation of mesenchymal stem cells derived from pancreatic islets and bone marrow into islet-like cell phenotype.
Source
Molecular Biotechnology Centre (MBC), University of Turin, Turin, Italy.
Abstract
BACKGROUND:
Regarding regenerative medicine for diabetes, accessible sources of Mesenchymal Stem Cells (MSCs) for induction of insular beta cell differentiation may be as important as mastering the differentiation process itself.
METHODOLOGY/PRINCIPAL FINDINGS:
In the present work, stem cells from pancreatic islets (human islet-mesenchymal stem cells, HI-MSCs) and from human bone marrow (bone marrow mesenchymal stem cells, BM-MSCs) were cultured in custom-made serum-free medium, using suitable conditions in order to induce differentiation into Islet-like Cells (ILCs). HI-MSCs and BM-MSCs were positive for the MSC markers CD105, CD73, CD90, CD29. Following this induction, HI-MSC and BM-MSC formed evident islet-like structures in the culture flasks. To investigate functional modifications after induction to ILCs, ultrastructural analysis and immunofluorescence were performed. PDX1 (pancreatic duodenal homeobox gene-1), insulin, C peptide and Glut-2 were detected in HI-ILCs whereas BM-ILCs only expressed Glut-2 and insulin. Insulin was also detected in the culture medium following glucose stimulation, confirming an initial differentiation that resulted in glucose-sensitive endocrine secretion. In order to identify proteins that were modified following differentiation from basal MSC (HI-MSCs and BM-MSCs) to their HI-ILCs and BM-ILCs counterparts, proteomic analysis was performed. Three new proteins (APOA1, ATL2 and SODM) were present in both ILC types, while other detected proteins were verified to be unique to the single individual differentiated cells lines. Hierarchical analysis underscored the limited similarities between HI-MSCs and BM-MSCs after induction of differentiation, and the persistence of relevant differences related to cells of different origin.
CONCLUSIONS/SIGNIFICANCE:
Proteomic analysis highlighted differences in the MSCs according to site of origin, reflecting spontaneous differentiation and commitment. A more detailed understanding of protein assets may provide insights required to master the differentiation process of HI-MSCs to functional beta cells based only upon culture conditioning. These findings may open new strategies for the clinical use of BM-MSCs in diabetes.
Alkaline phosphatase: can it be considered as an indicator of liver fibrosis in non-alcoholic steatohepatitis with type 2 diabetes?
Source
Department of Endocrinology, Faculty of lstanbul Medicine, Istanbul University, Istanbul, Turkey. gonenckocabay@yahoo.com
Abstract
OBJECTIVE:
While isolated hepatosteatosis is a benign disease, in minority of cases non-alcoholic steatohepatitis (NASH) may even lead to cirrhosis in long-term. In order to find the stage of the disease and determine the prognosis, a liver biopsy is indicated. In this study, we studied the relationship of liver histopathological findings with serum levels of hepatic enzymes.
METHODS:
We recruited 52 cases of NASH with Type 2 diabetes mellitus. Diagnosis of NASH was made based on biochemical tests, ultrasound images and liver biopsy.
RESULTS:
Steatosis was mild in 57.7%, moderate in 30.8%, and severe in 11.6% of patients. While no infiltration was found in 78.8% of cases, there was a grade-1 infiltration in 15.4% and a grade-2 infiltration in 5.8% of cases. Similarly, no fibrosis was found in 42.3% of patients, but there was a stage-1 fibrosis in 50%, and a stage-2 fibrosis in 7.7% of cases. In patients with severe steatosis, serum levels of AST were higher than mild or moderate stage steatosis. Accordingly, in patients with no inflammation, serum levels of ALT were higher than in patients with inflammation. However, in patients with fibrosis, triglycerides levels were significantly lower and ALP was significantly higher than in patients without fibrosis. The correlation analysis indicated a positive association between serum levels of ALP and C-peptide.
CONCLUSION:
In addition to conventional risk factors such as age, presence of diabetes, female sex; higher levels of ALP may be considered as a risk factor linked to hepatic fibrosis in patients with NASH and type 2 diabetes (Tab. 6, Ref. 8).
- PMID:
- 22180989
- [PubMed - in process]
Prednisone affects inflammation, glucose tolerance, and bone turnover within hours of treatment in healthy individuals.
Source
E Kauh, Merck Sharp and Dohme Corp., Whitehouse Station, United States.
Abstract
Objective: Use of glucocorticoids for anti-inflammatory efficacy is limited by their side effects. This study examined, in the same individuals, prednisone's acute, dose-dependent effects on inflammation as well as biomarkers of glucose regulation and bone homeostasis.Design: In this randomized, double-blind, parallel-design trial of healthy adults demonstrating cutaneous allergen-induced hypersensitivity, patients received placebo or prednisone 10, 25, or 60 mg daily for 7 days.Methods: Effects on peripheral white blood cell count, ex-vivo whole blood lipopolysaccharide (LPS)-stimulated TNF-α release, and response to cutaneous allergen challenge were assessed concurrently with biomarkers for glucose tolerance and bone turnover.Results: Differential peripheral white blood cell counts changed significantly within hours of prednisone administration. Ex-vivo, LPS-stimulated TNF-α was significantly reduced by all prednisone doses on days 1 and 7. The late phase cutaneous allergen reaction was significantly reduced with prednisone 60 mg vs. placebo on days 1 and 7. Oral glucose tolerance tests revealed significant increases in glycemic excursion on days 1 and 7; whereas, increases in insulin and C-peptide excursions were more notable on day 7 with all doses of prednisone. The bone formation markers osteocalcin, PINP, and PICP decreased significantly on days 1 and 7 vs. placebo.Conclusions: In healthy, young adults, prednisone treatment has significant effects on glucose tolerance and bone formation markers within hours of treatment, in parallel with anti-inflammatory effects, after single doses as low as 10 mg.
Induction of insulin-dependent diabetes mellitus by total pancreatectomy for pancreatic islet transplantation in cynomolgus monkeys.
Source
Department of General Surgery, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
Abstract
BACKGROUND/PURPOSE:
In order to perform a preclinical trial of pancreatic islet transplantation (PIT) in nonhuman primates, insulin-dependent diabetes mellitus (IDDM) must be induced. Methods for IDDM induction are administration of streptozotocin (STZ) or total pancreatectomy (TP). While STZ-induced IDDM is not always reliable, TP is appropriate for IDDM induction. However, TP is very difficult because of the complex surgical procedure required, necessary confirmation of IDDM, and difficulty in postoperative management. In this study, we tried to establish a reliable IDDM model for PIT in cynomolgus monkeys.
METHODS:
TP was performed in 5 male cynomolgus monkeys (Macaca fascicularis). This was followed by scheduled measurements of blood glucose, C-peptide levels, insulin levels, oral intake, and insulin requirements. IDDM induction was confirmed by serum C-peptide levels and intravenous glucose tolerance test (IVGTT). Allogeneic PIT was performed 14 days later with immunosuppressive therapy.
RESULTS:
TP successfully induced IDDM in all animals, confirmed by reduction of fasting serum C-peptide levels. Negative responses of serum C-peptide levels and insulin in IVGTT provided further confirmation of IDDM induction. No mortality or morbidity was encountered in any of the animals.
CONCLUSIONS:
TP successfully induced IDDM for PIT in cynomolgus monkeys.
The antiapoptotic effects of sulphurous mineral water and sodium hydrosulphide on diabetic rat testes.
Source
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Abstract
Background/Aims: It is well known that diabetes mellitus is associated with the impairment of testicular function. In the present study, we aimed to study the effects of sulphurous mineral water or sodium hydrosulphide (NaHS) on apoptotic testicular damage in rats with streptozotocin (STZ)-induced diabetes. Methods: Sulphurous mineral water (as drinking water) or NaHS (14 μmol/kg body weight/day, I.P.) was administered for 7 wks to rats with STZ-induced diabetes. Results: Hyperglycaemia, an overproduction of glycated haemoglobin (HbA1C) and a decline in serum insulin, C-peptideand insulin-like growth factor-I (IGF-I) were observed in diabetic rats. A decline in the serum testosterone level and an impairment of spermatogenesis, as indicated by a histopathological examination of diabetic rats, demonstrated significant testicular damage. Sulphurous mineral water and NaHS treatment may have improved the level of testicular GSH by blocking the overexpression of some apoptosis-related regulatory proteins such as Bax/Bcl-2, cytochrome c, caspase-9 and -3, and p53. This anti-apoptotic potential was associated with an increase in serum testosterone level and the amelioration of hyperglycaemia-related biochemical parameters. The histopathological examination was in harmony with the biochemical and molecular findings. Conclusion: Our study provides the first indication that sulphurous mineral water and NaHS may have a novel anti-apoptotic potential that could be a useful treatment in preventing diabetes-induced testicular dysfunction.
Copyright © 2011 S. Karger AG, Basel.
Species incompatibilities in the pig-to-macaque islet xenotransplant model affect transplant outcome: a comparison with allotransplantation.
Source
Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Abstract
Graham ML, Bellin MD, Papas KK, Hering BJ, Schuurman H-J. Species incompatibilities in the pig-to-macaque islet xenotransplant model affect transplant outcome: a comparison with allotransplantation. Xenotransplantation 2011; 18: 328-342. © 2011 John Wiley & Sons A/S. Abstract: Background: Porcine islet transplantation into diabetic non-human primates is considered most relevant in translational research supporting a clinical application. Most studies have focused on immunosuppressive protocols, while metabolic aspects have mainly been utilized in graft monitoring. We evaluated data from our group regarding human and non-human primate (NHP) allotransplantation and pig-to-NHP xenotransplantation to identify incompatibilities in metabolic factors and their consequences for transplant outcomes. Methods: Basic gluco-metabolic parameters (fasting blood glucose, C-peptide, and response to stimulation with arginine or glucose) were derived from literature (humans), 72 macaques, and 47 adult Landrace pigs. Islet preparations from 15 human deceased donors, 61 macaques, and 23 adult pigs were compared with respect to yield, fractional viability assessed by oxygen consumption normalized for DNA, and in vitro glucose-induced insulin release. Metabolic parameters at day 75 after a single islet transplantation in the liver were compared for 19 patients and 9 macaques receiving an allotransplant and 11 macaques receiving a porcine xenotransplant: recipients received chronic immunosuppression. Results: Pigs differ from NHPs and humans by a much lower C-peptide level (0.42 vs. 1.3 to 2.0 ng/ml, respectively) and a 2- to 7-fold lower C-peptide response to arginine stimulation. In contrast, NHPs have the highest metabolic demand as evidenced by a high C-peptide and high C-peptide response to arginine stimulation; values are about twice higher than in humans. For manufactured islet preparations, these differences are reflected by glucose-stimulated insulin release (the stimulation index for pigs is 1.5, for humans 3.8, and for macaques 7.7), but not by fractional viability, which was in the same range. The day 75 outcome after transplantation assessed by C-peptide was similar for allotransplanted humans and NHPs (80 to 90% good graft function) and lower in xenografted NHPs (36% good graft function); gluco-metabolic parameters were in accordance with graft function, albeit different between species because normoglycemia under exogenous insulin is maintained more aggressively in patients than in NHPs. In xenografted NHPs, the shift in glycemic control with respect to normal values, combined with low values of circulating porcine C-peptide, resembled more the normal condition in a pig than that in a macaque. Conclusions: The substantially lower glucose-induced insulin response in adult porcine islet preparations as opposed to islets manufactured from humans or macaques combined with the much higher need for insulin in macaques than in humans creates an imbalance between the metabolic demand and the engrafted islet mass in the pig-to-NHP xenograft recipient. Engrafted islet mass is affected by dose, suggesting that a much higher dose level of islets is necessary in the xenogeneic setting than in human or NHP allotransplantation, and pig islets need to be given at a higher dose in macaques than the anticipated effective dose in humans. To cope with differences in metabolic demand and presumably also metabolic dynamics, a liberal regime in supportive exogenous insulin might be essential to achieve long-term survival. These intrinsic characteristics of the NHP model deserve consideration to optimally design experimental studies with the perspective of translational value of results.
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