acid-phosphatase and Diabetes-Mellitus--Type-2

Renal dysfunction, a major complication of type 2 diabetes, can be predicted from estimated glomerular filtration rate (eGFR) and protein markers such as albumin concentration. Urinary protein biomarkers may be used to monitor or predict patient status. Urine samples were selected from patients enrolled in the retrospective diabetic kidney disease (DKD) study, including 35 with good and 19 with poor prognosis. After removal of albumin and immunoglobulin, the remaining proteins were reduced, alkylated, digested, and analyzed qualitatively and quantitatively with a nano LC-MS platform. Each protein was identified, and its concentration normalized to that of creatinine. A prognostic model of DKD was formulated based on the adjusted quantities of each protein in the two groups. Of 1296 proteins identified in the 54 urine samples, 66 were differentially abundant in the two groups (area under the curve (AUC):

Topics: Acid Phosphatase; Adult; Aged; Biomarkers; Calcium-Binding Proteins; Case-Control Studies; Cathepsin A; Chromatography, Liquid; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Extracellular Matrix Proteins; Female; G(M2) Activator Protein; Humans; Male; Mass Spectrometry; Middle Aged; Mucin-1; Prognosis; Proteomics; Retrospective Studies; Support Vector Machine; Urine

We evaluated the side effects of bisphosphonate (BP) on tooth extraction socket healing in spontaneously diabetic Torii (SDT) rats, an established model of non-obese type 2 diabetes mellitus, to develop an animal model of BP-related osteonecrosis of the jaws (BRONJ).. Male Sprague-Dawley (SD) rats and SDT rats were randomly assigned to the zoledronic acid (ZOL)-treated groups (SD/ZOL or SDT/ZOL) or to the control groups (SD/control or SDT/control). Rats in the SD/ZOL or SDT/ZOL groups received an intravenous bolus injection of ZOL (35 μg/kg) every 2 weeks. Each group consisted of 6 rats each. Twenty-one weeks after ZOL treatment began, the left maxillary molars were extracted. The rats were euthanized at 2, 4, or 8 weeks after tooth extraction, and the total maxillae were harvested for histological and histochemical studies.. In the oral cavity, bone exposure persisted at the tooth extraction site in all rats of the SDT/ZOL group until 8 weeks after tooth extraction. In contrast, there was no bone exposure in SD/control or SDT/control groups, and only 1 of 6 rats in the SD/ZOL group showed bone exposure. Histologically, necrotic bone areas with empty lacunae, microbial colonies, and less invasion by inflammatory cells were observed. The number of tartrate-resistant acid phosphatase-positive osteoclasts was lower in the SDT/ZOL group than in the SD/control group. The mineral apposition rate was significantly lower in the SDT/ZOL group compared with the SD/control group.. This study demonstrated the development of BRONJ-like lesions in rats and suggested that low bone turnover with less inflammatory cell infiltration plays an important role in the development of BRONJ.

Topics: Acid Phosphatase; Animals; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density; Bone Remodeling; Diabetes Mellitus, Type 2; Diphosphonates; Disease Models, Animal; Gene Expression; Humans; Imidazoles; Injections, Intravenous; Isoenzymes; Male; Maxilla; Molar; Osteoclasts; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Tartrate-Resistant Acid Phosphatase; Tooth Extraction; Zoledronic Acid

Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism.. Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism.. Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined.. ucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = -0.303, p < 0.0001), hemoglobin A1C (ρ = -0.214, p < 0.01), and glycated albumin (ρ = -0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH].. Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Blood Glucose; Bone Diseases, Metabolic; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Isoenzymes; Kidney Failure, Chronic; Male; Middle Aged; Osteocalcin; Renal Dialysis; Serum Albumin; Tartrate-Resistant Acid Phosphatase

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

Type 2 diabetics often demonstrate normal or increased bone mineral density, yet are at increased risk for bone fracture. Furthermore, the anti-diabetic oral thiazolidinediones (PPARgamma agonists) have recently been shown to increase bone fractures. To investigate the etiology of possible structural and/or material quality defects, we have utilized a well-described mouse model of Type 2 diabetes (MKR). MKR mice exhibit muscle hypoplasia from birth with reduced mass by the pre-diabetic age of 3 weeks. A compensatory hyperplasia ensues during early (5 weeks) development; by 6-8 weeks muscle is normal in structure and function. Adult whole-bone mechanical properties were determined by 4-point bending to test susceptibility to fracture. Micro-computed tomography and cortical bone histomorphometry were utilized to assess static and dynamic indices of structure, bone formation and resorption. Osteoclastogenesis assays were performed from bone marrow-derived non-adherent cells. The 8-week and 16-week, but not 3-week, male MKR had slender (i.e., narrow relative to length) femurs that were 20% weaker (p<0.05) relative to WT control femurs. Tissue-level mineral density was not affected. Impaired periosteal expansion during early diabetes resulted from 250% more, and 40% less of the cortical bone surface undergoing resorption and formation, respectively (p<0.05). Greater resorption persisted in adult MKR on both periosteal and endosteal surfaces. Differences were not limited to cortical bone as the distal femur metaphysis of 16 week MKR contained less trabecular bone and trabecular separation was greater than in WT by 60% (p<0.05). At all ages, MKR marrow-derived cultures demonstrated the ability for enhanced osteoclast differentiation in response to M-CSF and RANK-L. Taken together, the MKR mouse model suggests that skeletal fragility in Type 2 diabetes may arise from reduced transverse bone accrual and increased osteoclastogenesis during growth that is accelerated by the diabetic/hyperinsulinemic milieu. Further, these results emphasize the importance of evaluating diabetic bone based on morphology in addition to bone mass.

Topics: Acid Phosphatase; Animals; Biomechanical Phenomena; Bone Resorption; Diabetes Mellitus, Type 2; Femur; Isoenzymes; Male; Mice; Osteoclasts; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells; Tartrate-Resistant Acid Phosphatase; X-Ray Microtomography

Male hypogonadism is frequently associated with testopathy in patients with type 2 diabetes and in middle-aged males. We hypothesized that abnormal matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in testis have large roles to play in male hypogonadism. It has been found in diabetic rats that a novel compound, strontium fructose 1,6-diphosphate (FDP-Sr), with extra high energy supply, could reverse male hypogonadism by normalizing MMP-9 and TIMPs in the testis. We investigated whether FDP-Sr could be promising in treating diabetic testopathy.. Adult male Sprague-Dawley rats were administered a single dose of streptozocin (65 mg/kg, i.p.) to induce diabetes. The diabetic rats were treated with FDP-Sr in three doses or testosterone propionate in the final four weeks during the eight-week study.. Serum testosterone, activity of marker enzymes, and mRNA of MMPs and TIMPs and protein of MMP-9 in the testis were detected. After eight weeks, the activity of acid phosphatase, lactate dehydrogenase, succinate dehydrogenase and g-glutamyl transpeptidase in testis were significantly decreased (P < 0.01), accompanied by down-regulated mRNA and activity of MMP-2 and MMP-9 (P < 0.01) and upregulated mRNA of TIMP-1 and TIMP-2. Downregulated MMP-9 protein and degenerative changes in histology were predominant in diabetic testis.. FDP-Sr or testosterone propionate significantly normalized expression and activity of the MMPs-TIMPs system to attenuate changes in serum testosterone, marker enzymes and histology in testis. Effects of FDP-Sr were dose-dependent and comparable with those of testosterone propionate. By supplying extra energy, FDP-Sr could be promising in treating diabetic testopathy by normalizing abnormal MMP-9 and its endogenous inhibitors in testes.

Topics: Acid Phosphatase; Animals; Diabetes Complications; Diabetes Mellitus, Type 2; Disease Models, Animal; Dose-Response Relationship, Drug; Fructosediphosphates; gamma-Glutamyltransferase; Gene Expression; Hyperglycemia; Hypogonadism; L-Lactate Dehydrogenase; Male; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Rats; Rats, Sprague-Dawley; RNA, Messenger; Streptozocin; Succinate Dehydrogenase; Testis; Testosterone; Tissue Inhibitor of Metalloproteinases

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

To investigate the relationship of serum 25- Hydroxy D with bone mass density and other indicators in male patients with diabetes.. Bone mass density (BMD), serum 25- HydroxyD (25 (OH)VD) and several other biochemical indicators were measured in 82 male patients with diabetes, among whom 49 had osteoporosis.. The diabetic patients with osteoporosis had higher tartrate-resistant acid phosphatase-5b (TRCAP-5b) and lower 25(OH)VD, testosterone (T), Dehydroepiandrosterone sulfate (DHEA-S), and bone-specific alkaline phosphatase (B-ALP) than those without osteoporosis (P < 0.05). The Parathormone (PTH) and albumin-creatinine ratio (UAlb/Cr) also increased in the diabetic patients with osteoporosis, but with no statistical significance. No difference was observed in glycosylated hemoglobin (HBA1c) between the diabetic patients with and without osteoporosis. The serum 25(OH)VD was negatively correlated with the duration of diabetes in both groups (P < 0.05), which was independent from the increase of age. The serum 25(OH)VD was positively correlated with T score of neck, ward, greater trochanter of femur and vertebrae lumbales, and T and DHEA-S in both patients with and without osteoporosis (P < 0.05). The 25(OH)VD was also positively correlated with PTH in the patients with osteoporosis. Negative correlation was noted between 25(OH)VD and B-ALP. There were no correlations between 25(OH)VD and TRCAP-5b, HBA1c and UAlb/Cr.. Serum 25(OH)VD, T and DHEA-S may play an important role in the development of osteoporosis in male patients with diabetes mellitus.

Topics: Acid Phosphatase; Adult; Aged; Bone Density; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 2; Humans; Isoenzymes; Male; Middle Aged; Osteoporosis; Tartrate-Resistant Acid Phosphatase; Testosterone; Vitamin D

In order to investigate the underlying mechanism of alterations in bone mineral metabolism in patients with type 2 diabetes, we determined circulating levels of bone functional markers along with urinary excretion of sorbitol (SOR) and bone mineral density (BMD), and also examined their mutual interrelationship. A total of 151 male type 2 diabetic patients were examined in this study. Forty-eight age-matched male healthy subjects were also studied as the controls. A significant reduction of serum intact osteocalcin (i-OC) was found in the diabetic groups (p<0.01). On the other hand, circulating levels of tartrate resistant acid phosphatase (TRAP) in the diabetic patients were significantly higher than those in the controls (p<0.01). Interestingly, a significantly negative relationship was observed between BMD and serum TRAP (p<0.01), although no significant relationship was noted between BMD and serum i-OC in diabetic patients. Urinary excretion of SOR was significantly elevated in the diabetic patients when compared with the controls (p<0.01). In addition, a significantly positive correlation was observed between serum TRAP and urinary SOR (p<0.01), but not between serum i-OC and urinary SOR. Elevated serum TRAP in diabetes was reduced after the administration of aldose reductase inhibitor (p<0.05). It seems most likely that the increase in osteoclastic function probably due to accelerated polyol pathway plays a crucial role in the pathogenesis of decreased bone mineral content in male patients with type 2 diabetes.

Topics: Acid Phosphatase; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Diabetes Mellitus, Type 2; Humans; Isoenzymes; L-Iditol 2-Dehydrogenase; Male; Middle Aged; Osteocalcin; Polymers; Signal Transduction; Sorbitol; Tartrate-Resistant Acid Phosphatase

To clarify the pathogenesis of altered bone metabolism in diabetic state and its underlying mechanisms, the bone mineral content and fasting levels of serum intact parathyroid hormone (i-PTH), intact osteocalcin (i-OC), tartrate-resistant acid phosphatase (TRAP) and osteoclastgenesis inhibitory factor/osteoprotegerin (OCIF/OPG) were measured in male type 2 diabetic patients and their age-matched controls. In addition, urine levels of osteoclastic markers, C-telopeptide of type I collagen (CTx), deoxypyridinoline (DPD), and N-telopeptide of type I collagen (NTx) were simultaneously determined. Serum levels of i-PTH and i-OC in diabetic patients were significantly lower than those in the controls. Conversely, serum concentrations of TRAP were significantly elevated in diabetic patients. However, no clear correlation was observed between serum i-OC and TRAP. It was also observed that urinary excretion of CTx, DPD, and NTx was significantly increased in the diabetics as compared with the controls. Unexpectedly, serum levels of OCIF/OPG tended to be higher in the diabetic group, and these values exhibited a significantly positive correlation with those of serum TRAP. There was found a significantly negative correlation between serum TRAP and bone mineral density (BMD) and also between serum OCIF/OPG and bone mineral density. It seems probable that OCIF/OPG has a suppressive role on the increased bone resorption to prevent further loss of the skeletal bone mass in type 2 diabetic patients.

Topics: Acid Phosphatase; Amino Acids; Biomarkers; Bone Density; C-Peptide; Calcitriol; Calcium; Collagen; Collagen Type I; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Glycoproteins; Humans; Insulin; Isoenzymes; Magnesium; Male; Middle Aged; Osteocalcin; Osteoclasts; Osteoprotegerin; Parathyroid Hormone; Peptides; Phosphorus; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Sex Factors; Tartrate-Resistant Acid Phosphatase

Acid phosphatase locus 1 (ACP1) is a highly polymorphic enzyme that has an important role in flavoenzyme activity and in the control of insulin receptor activity and band 3 protein phosphorylation status. Adenosine deaminase (ADA) is a polymorphic enzyme that catalyses the irreversible deamination of adenosine to inosine and has an important role in regulating adenosine concentration. Based on the hypothesis that ACP1 counteracts insulin signaling by dephosphorylating the insulin receptor and that adenosine has an anti-insulin action, we reasoned that low ACP1 activity (low dephosphorylating action on insulin receptor) when associated with high ADA activity (low adenosine concentration) would result in a cumulative effect towards an increased glucose tolerance. On the contrary, high ACP1 activity when associated with low ADA activity would result in a cumulative effect towards a decreased glucose tolerance. A total of 280 adult subjects with type 2 diabetes from the population of Penne (Italy) were studied. There was a nonsignificant trend toward an increase in the proportion of subjects with the complex type with high ACP1 activity and low ADA activity (ie, *B/*B; *A/*C; *B/*C; *C/*C//ADA*1/*2 and *2/*2) in type 2 diabetes relative to that observed in newborn infants from the same population. High ACP1 activity/low ADA activity joint genotype was positively associated with high glycemic levels and with high body mass index (BMI) values. Low ACP1 activity/high ADA activity joint genotype was also positively associated with dyslipidemia. These findings suggest that both ACP1 and ADA contribute to the clinical manifestations of type 2 diabetes and probably also have a marginal influence on susceptibility to the disease. Both additive and epistatic interactions between the 2 systems seem to be operative.

Topics: Acid Phosphatase; Adenosine Deaminase; Adult; Aged; Aged, 80 and over; Body Mass Index; Diabetes Mellitus, Type 2; Electrophoresis, Starch Gel; Erythrocytes; Female; Genotype; Glycated Hemoglobin; Humans; Hyperlipidemias; Infant, Newborn; Male; Middle Aged; Phenotype; Polymorphism, Genetic; Signal Transduction

The acid phosphatase (ACP1) locus codes for a low molecular weight protein tyrosine phosphatase (LMPTP) that is found ubiquitously in human tissues. The *A allele of the ACP1 gene is associated with lower total enzymatic activity than the *B and *C alleles. An association between the *A allele and extreme values of body-mass-index (BMI) and dyslipidemia has previously been described in several samples of obese subjects from the Italian population. In the present study, we investigated the relationship between ACP1 *A allele genotypes (*A/*A, *A/*B, and *A/*C) and non-*A allele genotypes (*B/*B, *B/*C, and *C/*C) and metabolic variables in 277 Caucasian post-menopausal subjects consisting of 82 non-obese subjects (BMI/=35) subjects. ACP1 genotypes were found to be significantly associated with total cholesterol (p

Topics: Acid Phosphatase; Analysis of Variance; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Isoenzymes; Middle Aged; Obesity; Protein Tyrosine Phosphatases; Proto-Oncogene Proteins; Triglycerides

The ability of insulin to influence activities of various protein kinases and protein phosphatases, that are thought to mediate insulin action, are limited in patients with insulin resistance. Because numerous responses to insulin are affected, we undertook studies to determine whether protein tyrosine phosphatases (PTPs) activities are altered in patients with diabetes syndrome. In order to evaluate abnormal PTP activities, we done a comparative study using erythrocytes from normal and diabetic patients. We determined the activity of the cytosolic acid PTP in basal and insulin-dependent states. Mean basal PTP activities, were found to be significantly higher in diabetics than in normal subjects (type 1 diabetics: 0.36 +/- 0.01 vs 0.28 +/- 0.01 mmol p-nitrophenolate/h per g hemoglobin (Hb), P < 0.001; type 2 diabetics: 0.35 +/- 0.01 vs 0.28 +/- 0.01 mmol p-nitrophenolate/h per g Hb, P < 0.001). Insulin, at concentrations above physiological levels (1 mIU/ml), inhibited the PTP activities in erythrocytes from normal subjects (-15 +/- 4.1%, P < 0.01). Insulin could also modulate glycolysis, probably as a consequence of receptor tyrosine kinase activation, inducing phosphorylation of protein band 3 and hence the release of glycolytic enzymes. We have previously reported that a reductase enzyme in human erythrocytes is dependent on glycolysis being significantly activated (+28 +/- 3.1%, P < 0.001) by high insulin levels (1 mIU/ml). Mean basal reductase activities were found to be significantly lower in diabetics than in normal subjects (type 1 diabetics: 0.77 +/- 0.03 vs 0.97 +/- 0.02 mmol ferrocyanide/20 min per l cells, P < 0.001; type 2 diabetics: 0.77 +/- 0.04 vs 0.97 +/- 0.02 mmol ferrocyanide/20 min per l cells, P < 0.001), indicating altered erythrocyte metabolism in the diabetic patients. High glucose levels were used to mimic hyperglycemia condition, using erythrocytes from normal subjects. At 30 mM glucose, erythrocytic phosphatase activity was stimulated (+32 +/- 4.2%, P < 0.0001), although no effect was observed on the reductase enzyme at the same glucose levels. Results indicated that diabetic disorders appear to be associated with quantitative alterations of erythrocyte acid phosphatase activity and other enzymes that depend on the glycolytic rate (reductase). The overall data suggest that erythrocyte acid phosphatase may have a role in the modulation of glycolytic rates through the control of insulin receptor phosphorylation.

Topics: Acid Phosphatase; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Erythrocytes; Female; Glucose; Glycated Hemoglobin; Humans; Insulin; Kinetics; Male; Middle Aged; NADH, NADPH Oxidoreductases; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Reference Values

We have studied a new sample of 276 NIDDM patients from the population of Penne (Italy). Comparison of the new data with those of 214 diabetic pregnant women from the population of Rome reported in a previous paper has shown that the pattern of association between low molecular weight acid phosphatase genotype and degree of glycemic control is similar in the two classes of diabetic patients. Among nonobese subjects the proportion of ACP1*A (the allele showing the lowest enzymatic activity) is lower in diabetic patients with high glycemic levels (mean value greater than 8.9 mmol/l) than in diabetic patients with a low glycemic level (mean value less than 8.9 mmol/l). Among obese subjects no significant association is observed between glycemic levels and ACP1. Among nonobese subjects the concentration of f isoform of ACP1 is higher in patients showing a high glycemic level than in patients showing a low glycemic level. No significant difference is observed for s isoform.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Genotype; Humans; Isoenzymes; Male; Middle Aged; Molecular Weight; Obesity; Pregnancy; Pregnancy in Diabetics

Low-molecular-weight acid phosphatase (ACP1) is a polymorphic protein-tyrosine phosphatase present in all human tissues, including adipocytes. A positive association between the low-activity ACP1*A/*A genotype and extreme body mass index has previously been shown by us in obese subjects from the population of Rome. We have now studied a sample of 265 subjects with non-insulin-dependent diabetes mellitus (NIDDM) from another Italian population. There is a significant interaction between ACP1, body mass index, and blood lipid level. A highly significant positive association between ACP1*A/*A and high body mass index similar to that previously observed in obese subjects from the population of Rome is present only in those NIDDM subjects with blood lipid levels within the normal range. In NIDDM subjects the low-activity ACP1*A/*A variant seems to favor the increase of body mass or blood lipid levels or both. The pattern of association is independent of sex, age at survey, age at onset of diabetes, duration of disease, and therapy.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Body Mass Index; Diabetes Mellitus, Type 2; Female; Genotype; Humans; Italy; Lipids; Male; Middle Aged; Obesity; Polymorphism, Genetic

Cytosolic low molecular weight acid phosphatase (ACP1) is a high polymorphic phosphotyrosine-protein-phosphatase involved in signal transduction. In NIDDM subjects we have found that ACP1 genotype is a highly significant predictor of retinopathy, suggesting that genetic variability of signal transduction may have an important role in the susceptibility to this complication. Adenosine deaminase, ABO blood groups and several clinical variables have been also considered. The results point out the importance of interactions between genetic systems. Among non-genetic variables dislipidemia and treatment with insulin are significantly associated with retinopathy.

Topics: Acid Phosphatase; Adenosine Deaminase; Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Regression Analysis; Signal Transduction

Low molecular weight acid phosphatase encoded by the highly polymorphic locus ACP1 is a member of the protein-tyrosin phosphatase family (PTPases) which plays an essential role in the control of receptor signalling through phosphotyrosine pathways. Recent experiments have shown that purified rat liver ACP, corresponding to human ACP1, is able to hydrolyze a phosphotyrosine-containing synthetic peptide corresponding to the 1146-1158 sequence of the human insulin receptor, and shows a high affinity for it. This prompted us to analyze the degree of glycemic control in relation to ACP1 genetic variability in a sample of 214 diabetic pregnant women including IDDM, NIDDM and gestational diabetes. The ACP1 genotype was also determined in 482 non-diabetic pregnant women. In diabetic women glycemic levels in the last trimester of pregnancy appear to be significantly associated with the ACP1 genotype, and correlate positively with ACP1 enzymatic activity. The data suggest that quantitative variations of ACP1 may influence the clinical manifestations of diabetic disorders, and call for further studies on the role of this enzyme in the modulation of insulin-receptor phosphotyrosine pathways.

Topics: Acid Phosphatase; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Genetic Variation; Genotype; Humans; Molecular Weight; Pregnancy; Pregnancy in Diabetics