Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the past 4 years this author has treated almost 300 patients with Megace (megestrol acetate) for periods ranging from 6 weeks to 18 months and, in a few instances, longer. Most of the patients received Megace alone, with the remaining group receiving it in combination with 4 other compounds. The development of diabetes mellitus as described in the paper by J.C. Bottino and C.K. Tashima was not observed in any patients. The majority of patients had SMA 12/60 profiles at 6-week intervals during the 1st several months on therapy and later at about 2-month intervals including blood sugars. The several patients who had controlled adult diabetes when placed on Megace therapy alone or in combination developed no exacerbation of their diabetes while on this steroid. All of the patients received 40 mg 4 times daily throughout the period they were on Megace. It is this author's opinion that in the case described by Bottino and Tashima the development of diabetes mellitus was simply coincidental. This opinion is based on the treatment of a large number of patients with this compound.
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PMID:Megace and no diabetes mellitus. 84 8

The screening practices of 146 members of the Society of Teachers of Family Medicine (STFM) and 129 members of the American Academy of Family Physicians (AAFP) are compared. The screening practices of physicians from the two organizations were generally similar for psychosocial and behavioral problems, many forms of cancer, and numerous other conditions considered for inclusion in the routine periodic screening of asymptomatic individuals. However, for numerous diseases and tests, the screening practices of physicians from the two groups were significantly different. AAFP physicians were more likely to screen for lung and skin cancer, thyroid dysfunction, diabetes, and anemia, AAFP physicians were more likely to utilize chest x-ray, ECG, urinalysis, and SMA 6/12. STFM physicians were more likely to perform gonoccocal culture and tetanus-diphtheria immunization as well as to inquire about seat belt use. Three variables were found to predict physician screening practices as well as to account for the differences found between physicians drawn from the two organizations: completion of a residency in family medicine, year of graduation from medical school, and number of patients seen per week. Physicians reported practices were compared with recommendations in the major critical reviews: Frame and Carlson, Breslow and Sommers, the Canadian Task Force, and the American Cancer Society. For a number of tests and diseases physicians' reported practices were divergent with recent recommendations.
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PMID:Screening practices of family physicians: a comparison of STFM and AAFP members. 367 72

160 children and young adults (aged 7-21 years) and 84 diabetics (aged 2-19 years) were screened for thyroglobulin (TgA), thyroid microsomal (MsA), smooth muscle (SMA), parietal cell (PCA), reticulin (RA), glomerular (GIA) and mitochondrial (MA) antibodies. The diabetics were also screened for islet cell antibodies (ICA). The overall incidence of other antibodies than ICA at the lowest serum titre studied was 18.1 percent for healthy children and 30.9% for diabetic children. The elevation in diabetics is significant (p less than 0.01). Females were overrepresented in both groups and had the highest titres of antibodies. The age group 10-14 years was observed to be a special time at which antibody titres became positive. As compared with the controls, diabetics exhibited an increased incidence of MsA (4.4 and 11.9% respectively, p less than 0.001), PCA (5.0 and 10.7% respectively, p less than 0.05) and RA (3.8 and 9.5% respectively, p less than 0.05). The presence of ICA or the duration of diabetes showed no correlation with other autoantibodies. The results indicate that autoantibodies at a low titre are a common phenomenon. Diabetics seem to be susceptible to react against their own tissue, which is probably associated with their increased frequency of autoimmune diseases.
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PMID:Organ-specific antibodies in healthy and diabetic children and young adults. 675 72

The aim of the current study was to characterize the effects of prolonged hyperglycemia on renal structure and function using a model of non-insulin-dependent diabetes mellitus: the Goto Kakizaki (GK) rat, which does not have confounding variables, such as hyperlipidemia, obesity, or elevated blood pressure. The data show that hyperglycemia in this model was not associated with the development of significant proteinuria, but it was associated with the development of definitive age-dependent renal structural changes. These changes consisted of thickening of glomerular basement membrane at 35 weeks and tubular basement membrane. This thickening was accompanied by marked glomerular hypertrophy resulting from a parallel increase in total capillary luminal volume and mesangial volume, but fractional capillary and mesangial volumes remained unchanged. There was evidence of podocyte injury, as assessed by de novo expression of desmin. In contrast, there was no evidence of mesangial cell activation, as assessed by their de novo expression of alpha-SMA. Interstitial monocyte/macrophage influx increased significantly in GK rats at 12 weeks compared with Wistar controls. Glomerular macrophage infiltration was elevated significantly in 35-week GK rats. The structural changes described in the GK rat are similar to those described in prolonged non-insulin-dependent diabetes mellitus patients who have not developed overt renal disease. This model allows us to investigate further the mechanisms involved in the pathogenesis of the consequences of prolonged hyperglycemia.
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PMID:Association of prolonged hyperglycemia with glomerular hypertrophy and renal basement membrane thickening in the Goto Kakizaki model of non-insulin-dependent diabetes mellitus. 1115 83

Paraoxonase (PON) is an antioxidative enzyme, which eliminates lipid peroxides. PON has two common polymorphisms (M/L55 and R/Q192) that influence PON concentration and activity. We studied whether the M/L55 or R/Q192 genotype relates with the severity of atherosclerosis of the abdominal aorta, and the mesenteric and common iliac arteries in 123 consecutive autopsy cases (90 males and 33 females, aged 18-93 years). The severity of atherosclerosis in the arteries was evaluated, and the percentage of stenosis was measured. The intimal thickness in the internal elastic lamina (IEL) of the coeliac (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries were measured by light-microscopy. The LL homozygous men had more atherosclerotic plaques and complicated lesions in the common iliac arteries (56.8%) than the M allele carriers (28.3%, P=0.007). In logistic regression analysis, age (P<0.001) and the PON M/L55 genotype (P=0.015) were associated significantly with the severity of atherosclerosis in the common iliac arteries independent of smoking status, R/Q192 genotype, hypertension, diabetes mellitus, BMI and sex. The mean intima of the IMA was significantly thicker (P=0.035) and the number of stenotic lesions in SMAs significantly higher (P=0.008) in the LL homozygous men than M allele carriers. In turn, the R/Q192 genotype was not statistically significantly associated with plaque type, intimal thickness in the IEL or with the number of stenotic lesions. This study demonstrates that PON L55 homozygosity is an independent risk factor for autopsy-verified atherosclerosis in Finns.
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PMID:Paraoxonase producing PON1 gene M/L55 polymorphism is related to autopsy-verified artery-wall atherosclerosis. 1147 29

Insulin maintains vascular smooth muscle cell (VSMC) quiescence yet can also promote VSMC migration. The mechanisms by which insulin exerts these contrasting effects were examined using alpha-smooth muscle actin (alpha-SMA) as a marker of VSMC phenotype because alpha-SMA is highly expressed in quiescent but not migratory VSMC. Insulin alone maintained VSMC quiescence and modestly stimulated VSMC migration. Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, decreased insulin-stimulated expression of alpha-SMA mRNA by 26% and protein by 48% but had no effect on VSMC migration. PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, decreased insulin-induced VSMC migration by 52% but did not affect alpha-SMA levels. Platelet-derived growth factor (PDGF) promoted dedifferentiation of VSMC, and insulin counteracted this effect. Furthermore, insulin increased alpha-SMA mRNA and protein levels to 111 and 118%, respectively, after PDGF-induced dedifferentiation, an effect inhibited by wortmannin. In conclusion, insulin's ability to maintain VSMC quiescence and reverse the dedifferentiating influence of PDGF is mediated via the PI3K pathway, whereas insulin promotes VSMC migration via the MAPK pathway. Thus, with impaired PI 3-kinase signaling and intact MAPK signaling, as seen in insulin resistance, insulin may lose its ability to maintain VSMC quiescence and instead promote VSMC migration.
Diabetes 2003 Oct
PMID:Insulin affects vascular smooth muscle cell phenotype and migration via distinct signaling pathways. 1451 41

The initial phase of wound repair involves inflammation, induction of tissue factor (TF), formation of a fibrin matrix, and growth of new smooth muscle actin (alpha-SMA)-positive vessels. In diabetes, TF induction in response to cutaneous wounding, which ordinarily precedes increased expression of vascular endothelial growth factor (VEGF) and alpha-SMA transcription, is diminished, though not to a degree causing excessive local bleeding. Enhanced TF expression in wounds of diabetic mice caused by somatic TF gene transfer increased VEGF transcription and translation and, subsequently, enhanced formation of new blood vessels and elevated blood flow. Furthermore, increased levels of TF in wounds of diabetic mice enhanced wound healing; the time to achieve 50% wound closure was reduced from 5.5 days in untreated diabetic mice to 4.1 days in animals undergoing TF gene transfer (this was not statistically different from wound closure in nondiabetic mice). Thus, cutaneous wounds in diabetic mice display a relative deficiency of TF compared with nondiabetic controls, and this contributes to delayed wound repair. These data establish TF expression as an important link between the early inflammatory response to cutaneous wounding and reparative processes.
Diabetes 2005 Jul
PMID:Tissue factor as a link between wounding and tissue repair. 1598 16

Fatty liver in obese patients is emerging as one of the most common causes of chronic liver disease. Obese patients are at risk of developing type 2 diabetes mellitus (DM), and aggravating non-alcoholic fatty liver disease (NAFLD), developing into steatohepatitis (NASH) and hepatic fibrosis. Little is known of the possible impact on liver fibrogenesis of diabetes type 2 associated with obesity and NAFLD. Fifty-two morbidly obese patients were evaluated with complete clinical and laboratory medical assessment. Liver biopsy material was fixed in formalin, routinely processed to paraffin blocks, cut into 4-microm sections, stained with HE, PAS, Masson's trichrome and reticulin. Immunohistochemical stains included collagen IV, SMA and laminin. Within the initial group of 52, 25 patients had DM type 2, mean age 45.8 years. Patients with diabetes were older; had higher BMI, liver enzyme tests, glucose, cholesterol, and triglycerides; and lower albumin concentration. Livers of diabetics had significantly more severe steatosis and rich perisinusoidal collagen IV, laminin and SMA accumulation without histologically detectable NASH and irrespective of the degree of steatosis. Obese patients with type 2 DM and insulin resistance develop more severe NAFLD and early sinusoidal fibrosclerosis.
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PMID:Fibrogenesis in fatty liver associated with obesity and diabetes mellitus type 2. 1784 88

Peripheral artery disease and critical limb ischemia have become prevalent health risks in the United States due to an increasing elderly population and the prevalence of obesity and diabetes mellitus. Although highly invasive endarterectomy is the most popular method for treatment, angiogenic therapies based on growth factor administration are quickly becoming a popular alternative. Enzymatic degradation of these factors in vivo may be avoided by their incorporation in a delivery vehicle where the growth factor's release rate can be controlled by altering the vehicle's properties (i.e. cross-linking density, material selection, biodegradation, etc.). Herein, we report on the immobilization and controlled release of human recombinant basic fibroblast growth factor (FGF-2) and human recombinant granulocyte colony-stimulating factor (G-CSF) from ionic, gelatin-based hydrogel scaffolds to re-establish perfusion and induce capillary outgrowth in a murine hindlimb ischemic model. In vitro studies showed that endothelial cell proliferation was highly depended on FGF-2, whereas G-CSF stimulated migration and formation of a tubular network. When FGF-2 and G-CSF were used in combination there was an 82% increase in endothelial branch point formation compared to control groups. Leg reperfusion was assessed with laser Doppler perfusion imaging, while capillary outgrowth in the ischemic leg was evaluated using CD31(+) and alpha-SMA immunostaining. The co-delivery of G-CSF (1000 ngml(-1)) and FGF-2 (1000 ng ml(-1)) from the gelatin hydrogels resulted in a 3-fold increase in the perfusion levels and a 2-fold increase in capillary density and positive alpha-SMA vessels compared to the empty vehicle group. In conclusion, the co-delivery of FGF-2 and G-CSF was superior to bolus administration or the delivery of either factor alone in promoting reperfusion and mature vessel formation.
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PMID:Co-delivery of FGF-2 and G-CSF from gelatin-based hydrogels as angiogenic therapy in a murine critical limb ischemic model. 1871 69

Our first aim was to determine the effects of secreted clusterin (sCLU) and nuclear clusterin (nCLU) in diabetic nephropathy. We also aimed to investigate the post-effects of angiotensin II blockage treatment on clusterin expression and to compare these with apoptosis. Five groups of Wistar albino rats were used: First group consisted of healthy controls; the second group included the untreated STZ-diabetics; 30 days of irbesartan or perindopril treated STZ-diabetics formed the third and the fourth groups, respectively; while the subjects receiving a combined treatment with irbesartan and perindopril for 30 days consisted the fifth group. TUNEL method for apoptosis and immunohistochemical staining for TGF-beta1, alpha-SMA, clusterin-beta and clusterin-alpha/beta antibodies were performed. Apoptotic cells especially increased in the kidney tubuli of untreated diabetic group and on the contrary, a significant decrease was observed in the group that received a combined drug treatment. While sCLU was increased in the glomeruli and tubuli of the untreated diabetic group, it was decreased in all the treated groups. An increase in the nCLU immunoreactivity was observed in the podocytes, mesangial cells, and the injured tubule cells of the untreated diabetic group. nCLU immunopositive cells were decreased in all treated diabetic groups. In addition to this, the distribution of nCLU was similar to the distribution of apoptotic cells in the diabetic groups. Our results indicate that sCLU expression in diabetic nephropathy was induced due to renal tissue damage, and the nCLU expression increase in renal tubuli was related to apoptosis. Although irbesartan and perindopril prevented further renal injury in diabetes, a combined application of low-dose ACEI and AT1R blockers revealed more efficient measures, by means of renal damage prevention.
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PMID:The effects of ACE inhibitor and angiotensin receptor blocker on clusterin and apoptosis in the kidney tissue of streptozotocin-diabetic rats. 1894 65


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