Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunocytochemical assays (ICA) using monoclonal antiestrogen receptors (ER ICA), antiprogesterone receptors (PR ICA), and monoclonal antibody Ki67 (Ki67 ICA) were performed in 127 breast carcinomas. The immunostaining procedures were applied on frozen tissue sections, tumour imprints, and fine-needle aspirates in order to compare the variations in the distribution of the antigens detected in the three different types of preparations. Positive reactions detected with peroxidase-antiperoxidase and avidinbiotin-peroxidase, and alkaline phosphatase-antialkaline phosphatase complexes were evaluated through a computerized system of image analysis referred to as SAMBA 200 (SAMBA TITN, Grenoble, France). Application programs specifically developed for the analysis of tissue sections and of cytologic preparations were applied. This system allowed a multiparametric, accurate, reliable, reproducible and automatized evaluation of the heterogeneity of the antigenic sites in tumors. For each markers positive cell surface (PS), and integrated and mean optical densities (IOD, MOD) and IOD histograms were compared. It was shown that (1) there was no significant variation in optical densities in cell imprints and aspirates whereas PS significantly (P less than 0.01) differed in both preparations; (2) there were significant differences of the optical densities between tissue sections and cytological preparations, either imprints or aspirates, likely due to randomly cut nuclei in tissue sections; and (3) there was a significant difference between the PS of tissue sections and aspirates but no significant difference between tissue sections and imprints. It is concluded that fine-needle aspiration constitutes a convenient method for cell sampling, reliable for the diagnosis of malignancies. However, it may not reflect the heterogeneity of cell subpopulations in tissue.
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PMID:Immunodetection in fine-needle aspirates and multiparametric (SAMBA) image analysis. Receptors (monoclonal antiestrogen and antiprogesterone) and growth fraction (monoclonal Ki67) evaluation in breast carcinomas. 264 15

The effect of mild, non-insulin-dependent diabetes (NIDDM) on bone calcification and calcium (Ca) homeostasis was studied in growing rats (males and females). The diabetic state was characterized by mild insulin deficiency, plasma levels being 73% of controls, and mild hyperglycemia, with nonfasting plasma glucose levels of 1.5 times normal. There was no difference in plasma levels of Ca, phosphate (Pi), magnesium (Mg), alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), calcitonin, 25-(OH)vitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D), and 24,25-dihydroxyvitamin D (24,25[OH]2D) between the NIDDM rats and their controls of either sex. Metabolic Ca and Pi balance studies revealed that the experimental animals of both sexes were in positive Ca and Pi balance similar to that of their controls. Histologic studies of the kidney and intestinal slices from the experimental group were normal. Ca and Pi bone content calculated per gram bone ash of the femur, mandible, and second and fourth caudal vertebrae, and the organic content in the bones of the NIDDM animals showed no difference from their controls. Femur bone density and tibial epiphyseal growth plate width and morphology were similar histologically in the experimental and control rats. No decreased osteoid content in the tibial bone was found in the diabetic rats compared with controls. Physiologic sex differences, consisting of lower plasma Pi, higher plasma calcitonin levels, increased ratio of femur dry bone weight to total body weight, and increased percentage of mineralized and total bone volume at the tibial metaphysis seen in female compared with male control rats were also seen in the diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone calcification and calcium homeostasis in rats with non-insulin-dependent diabetes induced by streptozocin. 397 85

It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulin-dependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44.1 +/- 7.2 to 31.5 +/- 7.2 (S.E.M.) mmol/l (P = 0.001), and insulin and C-peptide levels fell from 920 +/- 62 to 542 +/- 45 mU/l (P = 0.008) and 5466 +/- 633 to 3071 +/- 297 pmol/l (P = 0.02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48 +/- 10.2 to 410 +/- 50.1 micrograms/l (P = 0.001), and those of IGF-II fell from 279.8 +/- 8.3 to 104.3 +/- 7.9 micrograms/l (P = 0.001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655 +/- 127 to 2197 +/- 334 micrograms/l (P = 0.002), despite a significant fall in GH concentrations from 10.7 +/- 2.6 to 4.1 +/- 1.1 mU/l (P = 0.007), suggesting that IGFBP-3 regulation is also IGF-I-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) and IGFBP-3 to IGF-I treatment in severe insulin resistance. 751 62

Testicular peritubular and prostatic stromal cells produce extracellular matrix elements and paracrine factors that modulate the cytodifferentiation and function of the corresponding epithelial cells. The present paper describes the establishment and characterization of five rat testicular cell lines with peritubular characteristics and one prostatic stromal cell line. Four peritubular cell lines were isolated after transfection of a mixed peritubular-Sertoli cell culture with a v-myc-containing plasmid. The same immortalization procedure applied to prostatic stromal cells yielded one cell line. An additional testicular cell line arose by spontaneous immortalization during serial subculture. Except for one testicular cell line (RTC-8T1), the morphology of all of the immortalized cell lines strongly resembled that of primary cultures of peritubular and stromal cells. Flow cytometric analysis demonstrated that all cell lines scored positive for alpha-smooth muscle isoactin and negative for cytokeratins, confirming their myofibroblast-like nature. None of the cell lines, however, stained positive for alkaline phosphatase, and androgen receptor expression was also lost. Typical Leydig cell characteristics, such as steroidogenesis, and Sertoli cell markers, such as transferrin secretion, were absent. Coculture of the cell lines with Sertoli cells resulted in the formation of tubular structures. A cell attachment assay and an enzyme-linked immunosorbent assay for fibronectin confirmed the production of extracellular matrix elements by all of the established cell lines. Media conditioned by the cell lines stimulated Sertoli cell transferrin production. The active principle was partially purified and resembled the P-MOD-S-like factors produced by primary cultures of peritubular and stromal cells. It is concluded that the immortalized cell lines have retained several of the characteristics of primary cultures of peritubular and stromal cells and may be useful for further studies on mesenchymal-epithelial interactions in testis and prostate.
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PMID:Characterization of newly established testicular peritubular and prostatic stromal cell lines: potential use in the study of mesenchymal-epithelial interactions. 778 11

We measured lumbar bone mineral density (L2-4 MBMD) in the postmenopausal elderly diabetic women and made comparisons with age-matched controls in terms of the age, body mass index (BMI) and % BMD of age-matched. In addition we evaluated the correlation between BMD and menarche age, menopause age, HbA1c, serum calcium, serum phosphate, serum alkaline phosphatase (S-Alp) and the ratio of urine calcium to urine creatinine (UCa/Cr). Moreover we divided non-insulin dependent diabetic patients (NIDDM) into two groups; the high BMD group and the low BMD group. Serum Alp and the ratio of UCa/Cr were compared in these two groups. The relationships between regimen of therapy and BMD were also analyzed in female NIDDM. There were no significant differences of BMD and background factors between controls and NIDDM. The ratio of UCa/Cr in the high BMD group were significantly less than that in low BMD group (p < 0.05). BMD in NIDDM with retinopathy was lower, but not significantly, than that in NIDDM without retinopathy. The methods of therapy for NIDDM such as diet alone, an oral hypoglycemic agent and insulin did not influence BMD in elderly postmenopausal diabetics. These results indicated that BMD in elderly postmenopausal diabetics are dependent on UCa/Cr and retinopathy.
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PMID:[Bone mineral density in postmenopausal elderly women with type 2 diabetes]. 859 32

Patients with poorly controlled noninsulin dependent diabetes mellitus (NIDDM) are shown to have higher bone mass. However, the influence of changes in glycemic control on bone turnover is not known. To clarify whether metabolic improvement of poorly controlled NIDDM affects bone turnover, markers for glucose, mineral, and bone metabolism were assessed before and after glycemic control for 3 weeks in 78 poorly controlled NIDDM patients with initial hemoglobin A1c over 8%. Metabolic improvement caused a reduction in urinary calcium (Ca) and phosphate (Pi) and serum 1,25(OH)2D levels, and an increase in serum Pi without changes in serum Ca or parathyroid hormone levels. Bone resorption markers, urinary deoxypyridinoline (Dpd) and type I collagen carboxy-terminal telopeptide (CTx), as well as a bone formation marker, serum bone type alkaline phosphatase (BALP), were reduced. However, another bone formation marker, serum osteocalcin (OC), was low before treatment and was elevated after treatment. The decrease in Dpd, CTx and BALP, but not the increase in OC, correlated with each other and with the improvement in glycemic indices. In conclusion, metabolic improvement of poorly controlled NIDDM decreases bone turnover within a short period. Thus, glycemic control may protect NIDDM patients from bone loss. It is possible that serum OC is affected by hyperglycemia per se, and may not correctly reflect bone turnover.
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PMID:Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. 928 19

Investigations of liver function and histology were undertaken in thirty four patients with Fibrocalculous Pancreatic Diabetes (FCPD). The data obtained were compared with those of similarly aged members of a diabetic control group comprising twelve patients with Protein Deficient Diabetes Mellitus (PDDM), twelve with Type 1 diabetes or Insulin Dependent Diabetes Mellitus (IDDM) and four young patients with Type 2 Diabetes of Non-Insulin Dependent Diabetes Mellitus (NIDDM). None of them had apparent past or present liver disease. Elevations of serum ALT (SGPT) and alkaline phosphatase levels were fairly common and was often associated with mild fatty changes and occasionally with focal necrosis and inflammatory changes. Cirrhosis and inflammatory changes per se were infrequent and fatty changes per se did not occur. In contrast patients belonging to the other diabetic subsets were very occasionally afflicted with hepatic abnormalities or not afflicted at all. We propose that loss of hepatotrophic actions mediated by insulin and glucagon could initiate and/or enhance hepatic abnormalities in FCPD where deficiencies of insulin and glucagon coexist.
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PMID:Observations on hepatic structure and function in fibro-calculous pancreatic diabetes (FCPD) vis-a-vis other diabetic subtypes. 967 Jun 24

Osteoblast deficit plays a principal role in the development of diabetic osteopenia. We have previously reported that high glucose conditions impair the function of osteoblast-like MG-63 cells. This study was performed to assess the sensitivity of osteoblasts to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients with type 2 diabetes without insulin deficiency or overt diabetic complications. During stimulation with 1,25(OH)2D3 at 2.0 micrograms/day for 6 consecutive days in 9 type 2 diabetic patients, serum levels of bone alkaline phosphatase (BALP), osteocalcin (OC) and the carboxyterminal propeptide of type 1 procollagen, and the urinary excretion of pyridinoline and deoxypyridinoline (DPYR), were monitored. As parameters of glycemic control, the mean level of fasting plasma glucose (mFPG) throughout the 1,25(OH)2D3 stimulation test and the level of HbA1C were used. 1,25(OH)2D3 increased serum 1,25(OH)2D significantly by day 2, which was followed by a significant reduction in the serum level of intact parathyroid hormone. The maximal increment of serum OC adjusted for that of 1,25(OH)2D was negatively correlated with both mFPG and HbA1C levels (p < 0.05). Furthermore, the magnitude of 1,25(OH)2D3-induced bone resorption, as reflected by the maximal increase in urinary DPYR excretion, was negatively correlated with the mFPG level (p < 0.05). Basal BALP tended to be negatively correlated with HbA1C, although not to a significant extent. In conclusion, our findings would indicate that poor glycemic control impairs the responses of osteoblasts and osteoclasts to 1,25(OH)2D3 in normo-insulinemic type 2 diabetic patients.
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PMID:Poor glycemic control impairs the response of biochemical parameters of bone formation and resorption to exogenous 1,25-dihydroxyvitamin D3 in patients with type 2 diabetes. 1062 60

Poorly controlled type 2 or non-insulin dependent diabetes mellitus (NIDDM) patients exhibit high bone turnover, which decelerate with treatment according to the degree of improvement in glycemic control. In adults, higher bone turnover results in rapid bone loss. Therefore, deceleration of bone turnover is beneficial for bone. Troglitazone (Tro), a new anti-diabetic drug, is a thiazolidinedione (TZD) which promotes adipocyte differentiation by activating peroxisome proliferator activated receptor gamma (PPARgamma). Because, in the bone marrow, adipocytes and osteoblasts originate in common mesenchymal stem cells that are also essential for osteoclastogenesis, TZDs may directly affect bone metabolism. Thus, we examined the effects of Tro on metabolic bone markers in type 2 DM patients. Tro (400 mg/day) was administered to 33 type 2 DM patients for four weeks. The day before and four weeks after starting Tro, serum and urine samples were collected after overnight fasting. Metabolic bone markers and glycemic indices were assessed. As bone resorption markers, urinary free and total deoxypyridinoline as well as urinary collagen type I C-terminal telopeptide were measured; as bone formation markers, serum bone type and total alkaline phosphatase (BALP and ALP) levels along with osteocalcin (OC) were used. No significant changes in fasting plasma glucose or HbA1c levels were observed in our short-term treatment with Tro. All the bone resorption markers, BALP and ALP were significantly decreased. OC was not significantly changed. The discrepant changes of OC from all the other metabolic bone markers suggest limitation of the use of OC as a reliable bone formation marker in diabetics. Our results that Tro decreased metabolic bone markers before significantly improving glucose metabolism suggest that it has direct effects on bone and decreased bone turnover. TZDs may spare bone mass in NIDDM subjects through its dual effects on glucose and bone metabolism.
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PMID:Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus. 1072 55

The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. The membrane protein plasma cell membrane glycoprotein-1 (PC-1) has been identified as an inhibitor of insulin receptor tyrosine kinase (IRTK) activity. We investigated insulin receptor function and PC-1 levels in muscle from three groups of obese subjects: women with GDM, pregnant women with normal glucose tolerance, and nonpregnant control subjects. Subjects (n = 6 for each group) were similar in age and degree of obesity (body fat >30%). IRTK activity, insulin receptor tyrosine phosphorylation, and protein levels of membrane glycoprotein PC-1 were determined in rectus abdominus muscle biopsies obtained at the time of either elective cesarean section or gynecological surgery. No significant differences were evident in basal insulin receptor tyrosine phosphorylation or IRTK activity in the three groups. After maximal insulin (10(-7) mol/l) stimulation, IRTK activity measured with the artificial substrate poly(Glu,Tyr) increased in all subjects but was lower in women with GDM by 25% (P < 0.05) and 39% (P < 0.001) compared with pregnant and nonpregnant control subjects, respectively. Similarly, insulin receptor tyrosine phosphorylation was significantly decreased in subjects with GDM (P < 0.05) compared with pregnant and nonpregnant control subjects. Treatment of the insulin receptors with alkaline phosphatase to dephosphorylate serine/threonine residues increased insulin-stimulated IRTK activity significantly in pregnant control and GDM subjects (P < 0.05), but these rates were still lower compared with nonpregnant control subjects (P < 0.05). PC-1 content in muscle from GDM subjects was increased by 63% compared with pregnant control subjects (P < 0.05) and by 206% compared with nonpregnant control subjects (P < 0.001). PC-1 content was negatively correlated with insulin receptor phosphorylation (r = -0.55, P < 0.05) and IRTK activity (r = -0.66, P < 0.05). These results indicate that pregnant control and GDM subjects had increased PC-1 content and suggest excessive phosphorylation of serine/threonine residues in muscle insulin receptors and that both may contribute to decreased IRTK activity. These changes worsen in women with GDM when controlling for obesity. These postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life.
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PMID:Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 overexpression in skeletal muscle from obese women with gestational diabetes mellitus (GDM): evidence for increased serine/threonine phosphorylation in pregnancy and GDM. 1087 Nov 98


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