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

Expression under the control of the mouse transferrin promoter of a transgene encoding a soluble secreted derivative of the ectodomain of the human insulin receptor in transgenic mice results in the accumulation of this high-affinity insulin-binding protein in the plasma. Alterations of glucose homeostasis are observed including postabsorptive hyperglycemia concomitant with increased hepatic glucose production and hyperinsulinemia. Thus, this is the first transgenic animal model of chronic hyperglycemia with alterations in glucose homeostasis that are produced without a targeted alteration of pancreatic function. These mice provide a new experimental model to follow the progression and long-term consequences of chronic hyperglycemia.
Diabetes 1994 Jan
PMID:A new transgenic mouse model of chronic hyperglycemia. 750 43

To assess the effect of glucose, foetal calf serum (FCS) and iron-saturated transferrin (Fe-TRF) on DNA synthesis of fibroblast-free neonatal rat islets cultured in Ham's F-12 medium, we measured [3H]thymidine uptake in cultures and used immunohistochemistry to quantitate nuclear 5-bromo-2'-deoxyuridine staining. Addition of glucose to a concentration of 26.1 mmol/l resulted in a significant increase from baseline in DNA synthesis in islet cells as measured by both methods (22,591 counts/min per microgram DNA +/- 3628 S.E.M., vs. 9631 counts/min per microgram DNA +/- 1912 S.E.M., P < 0.002 and 19.19% positive beta-cells +/- 2.72 S.E.M., vs. 11.98 positive beta-cells +/- 0.26 S.E.M., P = 0.05). At a glucose concentration of 16.1 mmol/l we could demonstrate an increase compared with baseline only in [3H]thymidine uptake (15,700 counts/min per microgram DNA +/- 3323 S.E.M., P < 0.05). Supplementation with 10% or 15% FCS also increased [3H]thymidine uptake compared with baseline (to 15,809 counts/min per micrograms DNA +/- 136 +/- S.E.M., P < 0.05 and 23,746 counts/min per microgram DNA +/- 3114 S.E.M., P < 0.01, respectively) but did not significantly effect the BrDU labelling index. Addition of Fe-TRF to islet cultures significantly increased [3H]thymidine uptake at a concentration of 45 micrograms/ml compared with baseline (23,149 counts/min per microgram DNA +/- 6387 S.E.M., P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1995 Feb
PMID:DNA synthesis in cultured neonatal rat islets--a comparison of two methods. 760 49

A 54 year-old previously healthy woman was admitted with staphylococcus aureus septicaemia. The patient had been treated with oral iron supplementation for two years due to fatigue. In the evaluation of postinfectious anaemia, serum transferrin saturation and serum ferritin were found persistently elevated with values of 74% and 950 micrograms/1, respectively. Hereditary haemochromatosis was suspected even though there was no history of liver disease or diabetes mellitus in the family. A bone marrow biopsy showed a normal content of haemosiderin iron. The liver biopsy revealed haemosiderosis, mainly located to the periportal hepatocytes, and fibrosis in the portal tracts. The HLA-type was A3, B7, B37. Over a period of ten months, a total of 3.9 g of iron was removed by venesection while S-ferritin declined to 31 micrograms/l. A sister to the proband had an identical HLA type, but normal iron status markers, either indicating heterozygosity or homozygosity with lack of penetrance. In preclinical hereditary haemochromatosis, early diagnosis and treatment is essential in order to prevent organ damage and to improve prognosis. Prophylactic screening is recommended. The identification of one homozygous subject in a Danish year-cohort of 60.000 persons costs approximately 40.000 Danish kroner (7.000 US+).
 ...
PMID:[Preclinical hereditary hemochromatosis--is there an indication for preventive screening?]. 765 9

Insulin-dependent diabetes mellitus (IDDM) is a frequent complication in patients with beta-thalassaemia major. It is believed to be a consequence of the damage inflicted by iron overload to the pancreatic beta-cell. Liver disorders and genetic influences seem to be additional predisposing factors to diabetes mellitus in patients with beta-thalassaemia. Ethnic variations are frequently reported on prevalence and complications of diabetes mellitus in the beta-thalassaemia patients. We investigated 50 Saudi children (< 15 years) with beta-thalassaemia major and 50 beta-thalassaemia minor, and age- and sex-matched controls for the prevalence of diabetes mellitus, and its relation to hitherto claimed predisposing factors. Fasting blood glucose, plasma insulin level, liver function tests, plasma ferritin, iron, and transferrin were assessed in each patient and glucose tolerance was evaluated. Results in patients with beta-thalassaemia major were compared with those obtained for beta-thalassaemia minor and the controls. The results showed moderate elevation of ferritin level in the majority of the beta-thalassaemia major despite desferroxamine therapy. Either hyperinsulinaemia or hypoinsulinaemia was encountered in the majority of these patients. The prevalence of diabetes mellitus was 6 per cent compared to 2 per cent in the beta-thalassaemia minor and normal children. Impaired glucose tolerance (IGT) occurred at a significantly higher (24 per cent) frequency in the beta-thalassaemia major compared to 2 and 0 per cent in the beta-thalassaemia minor patients and normal controls, respectively. The prevalence of diabetes mellitus was significantly lower in the Saudi thalassaemic patients compared to the results obtained from patients of other ethnic groups reported in literature.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Diabetes mellitus in children suffering from beta-thalassaemia. 780 19

We report two brothers with complete caeruloplasmin deficiency. The brothers presented with dementia and diabetes mellitus. Twelve relatives have partial caeruloplasmin deficiency. There is no copper overload. Transmission is autosomal recessive. DNA analysis showed genetic linkage between the deficiency and various polymorphic markers flanking the caeruloplasmin gene on chromosome 3q25. This is consistent with a mutation of the caeruloplasmin gene. Caeruloplasmin catalyses the oxidation of ferrous iron to ferric iron. Both brothers have low serum iron and increased liver iron. The index patient was given caeruloplasmin-containing, fresh-frozen plasma. A dose of 2.6 mg caeruloplasmin increased serum iron from 5 microM/l to 10 microM/l. A dose of approximately 72 mg increased serum iron from 5 microM/l to 19 microM/l. The abnormal serum and liver iron levels, and the caeruloplasmin-induced rise in serum iron, confirm a previous suggestion that caeruloplasmin maintains the normal rate of flow of iron from store to transferrin. Dementia and diabetes mellitus have been described in only one other homozygote. The absence of copper overload, and the linkage of the deficiency with chromosome 3q25, distinguish this condition from Wilson's disease.
 ...
PMID:Hereditary caeruloplasmin deficiency, dementia and diabetes mellitus. 782 May 40

Our objective was to determine the role of increased glomerular clearance (GC) or reduced tubular reabsorption (TR) of transferrin in producing microtransferrinuria. An infusion of L-arginine was used to inhibit TR of transferrin, permitting the determination of both GC and TR of transferrin in 64 patients with non-insulin-dependent diabetes mellitus (NIDDM), with or without microtransferrinuria. Thirty-one healthy volunteers served as control subjects. The GC of transferrin in NIDDM patients with microtransferrinuria did not differ significantly from that in healthy controls or in NIDDM patients with normal transferrin excretion rates (TfER). No correlation was found between TfER and GC of transferrin in any group of the subjects. However, the TR of transferrin was inversely correlated with TfER in healthy controls and in the NIDDM patients, with or without microtransferrinuria. When transferrin absorption was plotted against the filtered load of transferrin, the regression lines for the three subject groups were parallel. The regression line for NIDDM patients with microtransferrinuria was shifted to the right of those for healthy controls and NIDDM patients with a normal TfER. These findings suggest that microtransferrinuria in patients with NIDDM is caused by the impaired tubular reabsorption of transferrin.
Diabetes Res Clin Pract 1994 Oct
PMID:Glomerular clearance and tubular reabsorption of transferrin in microtransferrinuric patients with non-insulin-dependent diabetes. 785 Dec 71

Hereditary hemochromatosis is a common disorder of iron metabolism with a prevalence as high as 8 per 1000. Affected individuals absorb excessive amounts of dietary iron and over time, tissue iron deposition results in skin discoloration, arthropathy, hepatic cirrhosis, heart failure, diabetes mellitus and impotence. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening. This conclusion is supported by cost-effectiveness analysis based on available data. A reasonable screening strategy would start with a serum transferrin saturation. A value > or = 55% should trigger a repeat transferrin saturation in a fasting state and a serum ferritin level. If both these tests are abnormal, a liver biopsy with quantitative iron determination is the currently accepted confirmatory test.
 ...
PMID:Management of hereditary hemochromatosis. 788 27

The clinical diagnosis of diabetes is often prompted by symptoms such as increased thirst and urine volume, and weight loss. High levels of glucosuria are usually present. A single blood glucose estimation of diagnostic value indicated > or = 200 mg/dl at random, or > or = 140 mg/dl at fasting in specimens of venous plasma. Only if blood glucose values lie in the uncertain range (i.e., between the level that establish or exclude diabetes) need an oral glucose tolerance test (OGTT) be considered in order to establish the diagnosis status. Diagnostic interpretation of the 75 g OGTT responses is performed by the criteria of the expert committee of the Japan Diabetic Society. Glycated hemoglobin (HbA1c, HbA1) is widely used as a cumulative estimate of the mean blood glucose concentration over the preceding one approximately two months. Reference ranges of HbA1c are 4 approximately 6%. Labile glycohemoglobin often influences the estimate. Fructosamine and glycated albumin are also used as means of evaluating the degree of control. These data reveal the mean blood glucose concentration over the preceding 2 weeks. 1.5-Anhydroglucitol in blood is measured as a means of diagnosis and control evaluation of diabetes. Microalbuminuria is widely measured for early detection of diabetic nephropathy. Recently other microproteinuria such as urinary transferrin and IgG are assayed for the same purpose. There are highly significant correlations between microalbuminuria and urinary transferrin or IgG.
 ...
PMID:[Clinical laboratory tests in diabetes mellitus]. 793 14

A 79-year-old native American female with a history of diabetes mellitus, but no history of hepatic or renal disease, presented with anasarca and hypoalbuminemia. Laboratory tests for fecal alpha 1-antitrypsin and an indium III-labeled plasma transferrin nuclear scan revealed a protein-losing enteropathy. A serological test was positive for antinuclear antibody in a titer of 1:1250 with a homogeneous pattern. This finding combined with low normal serum complement levels suggested the diagnosis of systemic lupus erythematosus (SLE). This case is unusual in that protein-losing enteropathy was the only presenting symptoms. The late onset of this disease is also unusual.
 ...
PMID:Primary lupus-associated protein-losing enteropathy. 804 95

An elevated concentration of carbohydrate-deficient transferrin in serum (CDT) has been reported to indicate excessive ethanol consumption. However, in hypertensive men, we found low values for diagnostic sensitivity and specificity. Furthermore, in the individuals with high CDT values, the concentrations of serum triglycerides and blood glucose were low rather than high, indicating that factors related to insulin/glucose metabolism may be operative. The current study addresses this issue by examining 48 patients with treated hypertension and at least 1 of following: hypercholesterolemia, history of smoking, and diabetes mellitus. We determined serum CDT, fasting plasma insulin, and glucose disposal rate during hyperinsulinemic euglycemic clamp. Seven patients had elevated CDT concentrations. This group of patients had higher glucose disposal rates than the others (mean difference, 19 mumol/min.kg lean body mass; 95% confidence interval, 5-33 mumol/min.kg lean body mass; P = 0.0096), but did not differ in body mass index or alcohol intake. Serum CDT correlated positively with glucose disposal rate (r = 0.55; P = 0.0004) and negatively with fasting plasma insulin (r = -0.43; P = 0.0039). These relationships remained after exclusion of 8 patients with diabetes mellitus and adjustment for potentially confounding factors. We conclude that the serum CDT concentrations in our patients were associated with insulin sensitivity.
 ...
PMID:Carbohydrate-deficient transferrin is associated with insulin sensitivity in hypertensive men. 807 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>