acid-phosphatase and Insulin-Resistance

We determined effects of bariatric weight loss surgery on serum tartrate-resistant acid phosphatase 5a (TRACP 5a), inflammatory cytokines and glucose homeostasis in severely obese Chinese adults.. Severely obese adults undergoing bariatric surgery were recruited. Anthropometry, insulin resistance (IR), inflammatory markers and serum TRACP 5a were measured at baseline and 3, 6 and 12months postoperatively.. Data of 93 patients, including 69 non-diabetic (non-DM group) and 24 diabetic (DM group), were analyzed. Anthropometry decreased significantly at 3months postoperatively in both groups; low-density lipoprotein cholesterol decreased obviously at 3, 6 and 12months in non-DM group, while improving significantly at 6 and 12months in DM group. Homeostasis model assessment for IR (HOMA-IR) improved significantly at 3, 6 and 12months in non-DM group and 12months in DM group. In DM group, C-reactive protein (CRP) decreased significantly at 3months postoperatively and inflammatory markers interleukin-6 (IL-6) and TRACP 5a improved at 6months postoperatively; in non-DM group, serum TRACP 5a decreased obviously at 12months postoperatively without significant changes in CRP and IL-6.. Weight reduction by bariatric surgery decreases anthropometry, IR, lipids and inflammatory markers in severely obese Chinese adults.

Topics: Acid Phosphatase; Adult; Asian People; Bariatric Surgery; Blood Glucose; C-Reactive Protein; Case-Control Studies; Cytokines; Female; Humans; Inflammation; Insulin Resistance; Isoenzymes; Lipids; Male; Obesity; Tartrate-Resistant Acid Phosphatase; Weight Loss

Aging may be a risk factor for type 2 diabetes in the elderly. Dietary intervention can affect glucose tolerance in adults, which may be due to body composition and islet cell autophagy. The aim of this study was to determine the effects of various dietary interventions on islet cell autophagy. Pancreatic tissue and blood samples were collected from Sprague Dawley rats (14-16 months old, n = 15 for each group) that received a normal diet (ND), a high-fat diet (HFD), or a calorie-restricted diet (CRD). The body weight (BW), visceral fat, serum lipid levels, fasting serum glucose, insulin levels, and β/α cell area were determined in 14-16-(0-w), 16-18-(8-w), and 18-20(16-w)-month-old rats. Pancreatic islet autophagy (LC3B and LAMP2), AP (Acid Phosphatase) and apoptosis (apoptosis index, AI (TUNEL assay) and cleaved caspase-3) were detected using immunohistochemistry, ELISA and western blot. At 16 weeks, the expressions of LC3B, LAMP2 and AP markedly increased in both the HFD (P<0.01) and CRD (P<0.05) groups; however, an increase in the AI (P<0.05), cleaved caspase-3 and Beclin1 expression and a decrease in the expressions of BCL2 and BCLXL (P<0.05) were observed in only the HFD group. FFA, triglyceride levels, HOMA-IR, insulin levels and glucagon levels were significantly increased in the HFD group but decreased in the CRD group at 16 weeks (P<0.05). The degree of islet cell autophagy was potentially regulated by the levels of FFA and islet cell insulin and glucagon, which may have been due to the effects of Beclin1/BCL2.

Topics: Acid Phosphatase; Animals; Autophagy; Blood Glucose; Body Weight; Caloric Restriction; Cellular Senescence; Diet, High-Fat; In Situ Nick-End Labeling; Insulin; Insulin Resistance; Intra-Abdominal Fat; Islets of Langerhans; Lipid Metabolism; Lysosomal-Associated Membrane Protein 2; Male; Microtubule-Associated Proteins; Random Allocation; Rats, Sprague-Dawley; Risk Factors

Recent animal studies have demonstrated that undercarboxylated osteocalcin upregulates insulin secretion via osteoblast-insulin signaling. However, it remains unclear whether such a pathway exists in humans. This study showed that serum undercarboxylated osteocalcin levels were inversely associated with fasting plasma glucose, hemoglobin A(1c), and homeostasis model assessment of insulin resistance (HOMA-IR) levels in community-dwelling elderly Japanese men.. Undercarboxylated osteocalcin (ucOC) was reported to increase insulin secretion and improve glucose tolerance via osteoblast-insulin signaling in animal-based studies. Whether this pathway also exists in humans is unknown. We aimed to clarify whether serum ucOC levels are associated with glycemic status and insulin resistance in the general Japanese population.. We included 2,174 Japanese men (≥65 years) who were able to walk without aid from others and lived at home in four cities of Nara Prefecture. We excluded participants with a history of diseases or medications that affect bone metabolism, other than type 2 diabetes mellitus (T2DM). Fasting plasma glucose, glycated hemoglobin A(1c), and HOMA-IR levels were determined as outcome measures.. Of the 1,597 participants included in the analysis, both intact OC (iOC) and ucOC levels showed significant inverse correlations with all outcome measures, even after adjusting for potential confounders. Mean values of outcome measures showed a significant decreasing trend with higher quintiles of iOC or ucOC after adjusting for confounders. This trend remained significant for ucOC quintiles after further adjustment for iOC levels, but was not significant for iOC quintiles after adjusting for ucOC levels. These results were attenuated, but still apparent, after excluding participants receiving drug therapy for T2DM.. Levels of ucOC, but not iOC, were inversely associated with glycemic index and insulin resistance in a population of Japanese men. These findings will need to be confirmed with longitudinal studies.

Topics: Acid Phosphatase; Aged; Anthropometry; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin Resistance; Isoenzymes; Japan; Life Style; Male; Osteocalcin; Signal Transduction; Tartrate-Resistant Acid Phosphatase

Tartrate-resistant acid phosphatase (TRAP) expressed by adipose tissue macrophages (ATMs) induces mice obesity and human adipocyte differentiation in vitro. This study aimed to investigate whether TRAP was secreted differently from human obese versus lean adipose tissues and to identify the cellular source of adipose tissue TRAP.. Subcutaneous adipose tissues obtained from healthy subjects. Enzyme-linked immunosorbent assays (ELISAs) for total (5a+5b) and cleaved TRAP (5b) were used. TRAP secretion was determined in adipose tissue biopsies, and mRNA expression was studied in cell types isolated from the same.. Results of 24 lean and 24 obese women (in vitro) and 8 subjects (in vivo) were compared. The main outcome measurements were TRAP expression and secretion in vitro and in vivo.. In-house total TRAP ELISA showed high sensitivity and a coefficient of variance of 11%. Adipose secretion of total TRAP was linear in vitro with time and was evident in vivo. Total TRAP secretion in vitro was similar in lean and obese women expressed per unit weight of the adipose tissue but correlated positively with the number/size of adipocytes (P ≤ 0.01) and with adipose secretion of tumor necrosis factor-α and interleukin-6 (P<0.01). TRAP 5b was not secreted from the adipose tissue. ATMs displayed highest cellular expression of TRAP mRNA in adipose tissue cells derived from lean or obese women.. TRAP is a novel human adipokine produced by macrophages and secreted from the subcutaneous adipose tissue in vivo and in vitro. Secretion is linked to the size and number of adipocytes, as well as to concomitant secretion of inflammatory mediators, suggesting that TRAP is involved in fat accumulation and adipose inflammation.

Topics: Acid Phosphatase; Adipokines; Adult; Aged; Analysis of Variance; Animals; Biomarkers; Body Weight; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Insulin Resistance; Interleukin-6; Isoenzymes; Macrophages; Male; Mice; Mice, Obese; Middle Aged; Obesity; RNA, Messenger; Subcutaneous Fat; Tartrate-Resistant Acid Phosphatase; Thinness; Tumor Necrosis Factor-alpha

The benefits of exercise on glucose metabolism, inflammation, and serum tartrate-resistant acid phosphatase 5a (TRACP 5a) protein levels in Chinese male adolescents have not been extensively analyzed. Therefore, we examined the effects of a 12-week exercise program on weight, adiposity, insulin sensitivity (IS), and inflammatory marker expression, including the novel macrophage marker TRACP 5a, in obese Chinese male adolescents. A total of 106 male adolescents were recruited from the Army Academy in Taiwan and classified as lean (body mass index [BMI], 20.9 +/- 0.2 kg/m(2)) or obese (BMI, 27.7 +/- 0.2 kg/m(2)). Body composition, IS, and inflammatory markers were measured in both groups at baseline and in the obese group after completion of a 12-week exercise program. Body weight, BMI, waist circumference, body fat mass and percentage, homeostasis model assessment for insulin resistance, fasting plasma glucose, fasting serum insulin, 2-hour postchallenge plasma glucose concentration, interleukin-6, C-reactive protein, and serum TRACP 5a were significantly higher in the obese group as compared with the lean group. In addition, serum TRACP 5a was positively correlated with body mass and fat indices. After completion of the exercise program, significant reductions in all anthropometric, metabolic, and inflammatory indicators, with the exception of serum TRACP 5a were observed. Although the obese participants remained obese, exercise training significantly improved IS and reduced interleukin-6 and C-reactive protein. Tartrate-resistant acid phosphatase 5a remained unaffected by exercise training, consistent with our hypothesis that it is associated with increased adipose tissue in obese individuals.

Topics: Acid Phosphatase; Adolescent; Blood Glucose; Body Mass Index; Cytokines; Exercise; Glucose Tolerance Test; Humans; Inflammation Mediators; Insulin; Insulin Resistance; Isoenzymes; Male; Obesity; Tartrate-Resistant Acid Phosphatase

It has been suggested that hormones released after nutrient absorption, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 2 (GLP-2), could be responsible for changes in bone resorption. However, information about the role of GLP-1 in this regard is scanty. Diabetes-related bone loss occurs as a consequence of poor control of glucose homeostasis, but the relationship between osteoporosis and type 2 diabetes remains unclear. Since GLP-1 is decreased in the latter condition, we evaluated some bone characteristics in streptozotocin-induced type 2 diabetic (T2D) and fructose-induced insulin-resistant (IR) rat models compared to normal (N) and the effect of GLP-1 or saline (control) treatment (3 days by osmotic pump). Blood was taken before and after treatment for plasma measurements; tibiae and femora were collected for gene expression of bone markers (RT-PCR) and structure (microCT) analysis. Compared to N, plasma glucose and insulin were, respectively, higher and lower in T2D; osteocalcin (OC) and tartrate-resistant alkaline phosphatase 5b were lower; phosphate in IR showed a tendency to be higher; PTH was not different in T2D and IR; all parameters were unchanged after GLP-1 infusion. Bone OC, osteoprotegerin (OPG) and RANKL mRNA were lower in T2D and IR; GLP-1 increased OC and OPG in all groups and RANKL in T2D. Compared to N, trabecular bone parameters showed an increased degree of anisotropy in T2D and IR, which was reduced after GLP-1. These findings show an insulin-independent anabolic effect of GLP-1 and suggest that GLP-1 could be a useful therapeutic agent for improving the deficient bone formation and bone structure associated with glucose intolerance.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Resorption; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucagon-Like Peptide 1; Glucose; Insulin; Insulin Resistance; Isoenzymes; Male; Osteocalcin; Osteoprotegerin; Parathyroid Hormone; Peptide Fragments; RANK Ligand; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase

Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP) is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer.. Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity.. Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

Topics: Acid Phosphatase; Adipose Tissue; Adult; Animals; Biomarkers; Blotting, Western; Body Weight; Dimerization; DNA Primers; Female; Humans; Immunoenzyme Techniques; Insulin Resistance; Isoenzymes; Lipogenesis; Lipolysis; Macrophages; Male; Mesenchymal Stem Cells; Mice; Mice, Obese; Mice, Transgenic; Obesity; Organ Size; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase