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)

The HLA of 56 unrelated Japanese with insulin-dependent diabetes mellitus (IDDM) was investigated and reconfirmed their role in the pathogenesis by restriction fragment length polymorphism (RFLP). DQw4 showed the highest correlation to IDDM not only within the DQ system but among all the antigens, suggesting that HLA-DQ might play the most important role in the development of IDDM similar as in Caucasians. When the amino acid sequences of DQA1 and DQB1 alleles were analyzed to find susceptibility to IDDM, common features were observed. That is, in any ethnic group, DQA1 alleles of non-Leu at 76th residue combined with DQB1 alleles of non-Asp at 57th residue show association with IDDM, whereas other combinations give rise to negative association. However, two exceptions were observed in case of Japanese IDDM patients with DQw4 and DQw9. Since DQw4 and DQw9 are in strong linkage disequilibrium with DRB1 containing non-Asp-57th, mixed isotype molecules of DQA1 and DRB1 might be responsible to determine IDDM susceptibility. Furthermore, several non-HLA genes, the polymorphism in the genes encoding the alpha (A), beta (B) and gamma (G) chains of the T-cell receptor (TCRA, TCRB and TCRG), insulin gene (INS) and three closely linked polymorphic genes on chromosome 11q23; Thy-1 (THY1), T3-D (CD3D) and c-ets proto oncogene (ETS1) were analyzed. Only the EST1 gene showed a significant association with IDDM by AvaII-polymorphic fragment (P less than 0.03). These results were discordant with some of the strongly associated genes observed in Caucasians. The discrepancy of the HLA and non-HLA results between both ethnic groups is discussed.
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PMID:HLA and non-HLA genetic factors in Japanese IDDM. 168 10

The method of flow cytometry employing monoclonal antibodies a Leu 7 (CD57), a Leu 11 (CD16) and a NKH-1 (CD56) was used to examine to content of different subpopulations of natural killer cells in the blood of primary patients with insulin-dependent diabetes mellitus and in healthy subjects. Patients with insulin-dependent diabetes mellitus showed as compared with healthy persons a lower content of natural killer cells carrying all the examined markers, in particular, CD56. The degree of reduction of the number of natural killer cells of different subpopulations is individual for each patient that, possibly, reflects the diversity of causes leading to development of the disease.
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PMID:[Natural killer cells of different immunological phenotypes (CD16+, CD56+ and CD57+) in the blood of patients with insulin-dependent diabetes mellitus]. 171 35

A low-protein diet (8 vs. 20%) administered during pregnancy affects the structure and function of the endocrine pancreas of the offspring. At 21.5 days of gestation, we reported a reduction of cell proliferation, islet size, islet vascularization, and pancreatic insulin content. In this study, we demonstrated an impairment of insulin secretion of these fetal islets when stimulated in vitro with amino acids such as arginine and leucine. If the offspring is kept on the same low-protein diet during suckling, weaning, and adulthood, fasting insulin levels remain low in the presence of normal blood glucose levels. Glucose tolerance at 70 days is impaired, with lower insulin response. In addition, permanent functional damage seems to be induced in utero by a low-protein diet, because a normal diet given from birth to adulthood does not restore normal insulin response after a glucose challenge. Our experimental results stress the impact of a balanced diet with qualitative and quantitative amino acid composition for the fetal endocrine pancreas to develop normally, without lasting functional and structural consequences in adulthood.
Diabetes 1991 Dec
PMID:Islet function in offspring of mothers on low-protein diet during gestation. 174 39

To assess the effect of insulin deficiency on whole body glutamine kinetics, five young adults with type I (insulin-dependent) diabetes received 4-h primed continuous infusions of L-[1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state after blood glucose had been clamped overnight at either a normoglycemic level (approximately 85 mg/dl) or a moderate hyperglycemic level (approximately 260 mg/dl) by means of an automated glucose control insulin infusion system. The hyperglycemic state was associated with a significant rise in leucine level [from 165 +/- 23 to 242 +/- 62 (SD) microM], appearance rate (from 125 +/- 11 to 142 +/- 17 mumol.kg-1.h-1), and oxidation (from 27 +/- 10 to 31 +/- 10 mumol.kg-1.h-1). In contrast, neither the plasma level nor the appearance rate of glutamine (333 +/- 51 vs. 318 +/- 58 mumol.kg-1.h-1) was affected. We conclude that insulin deficiency resulting in moderate hyperglycemia induces a 13% rise in whole body proteolysis and yet does not stimulate glutamine de novo synthesis, despite increased precursor availability.
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PMID:Glutamine nitrogen kinetics in insulin-dependent diabetic humans. 176 31

Acute effects of insulin on protein metabolism (whole body and forearm muscle) were simultaneously assessed using doubly labelled (13C15N) leucine in post-absorptive Type I diabetic patients. Whole body protein kinetics were calculated using either plasma 13C leucine or alpha-ketoisocaproic acid (alpha-KIC) enrichment to represent labelling of the precursor pool. Forearm muscle protein metabolism was measured using a previously described arterio-venous model. Acute insulin infusion (2-3 units per hour) for 2-3 hours reduced whole body protein breakdown (p < 0.01), synthesis (p < 0.05) and oxidation (p < 0.05) irrespective of the basis of calculation. Across forearm muscle, insulin reduced overall net negative protein balance (p < 0.05) by inhibiting protein breakdown, 80% and synthesis, 71%. Insulin reduced the deamination of leucine to alpha-KIC (p < 0.05) and its reamination (p < 0.05). This study demonstrates that whole body protein metabolism is broadly paralleled by events in skeletal muscle though the forearm approach is considerably more sensitive to noise than whole body protein kinetic measurements. This results from the less damped nature of the forearm model and the necessity to measure a greater number of variables required to solve the appropriate balance equations. Failure of insulin per se to promote protein synthesis in man is not model dependent and suggests that the observed differences relating to insulin mediated control of protein kinetics found in man compared with small mammals are both real and species related.
Diabetes Res 1991 Dec
PMID:Influence of insulin on leucine kinetics in the whole body and across the forearm in post-absorptive insulin dependent diabetic (type 1) patients. 184 50

Radioautography revealed data on protein synthesis dynamics in pancreacytes of intact mice, subjected to alloxan diabetes and isoproterenol (ISP) injection after synchronized secretion. Rhythmic fluctuation of protein synthesis with maximum uptake of 3H-leucine 40 and 80 min after treatment was observed in intact animals. The above maximums correlated with the increase in the cell size. In alloxan diabetes, injections of ISP and their combination the rhythm of protein synthesis is retained, the total intensity of isotope uptake increases significantly, but at the same time secretion periods, particularly in the latter case decrease. The results obtained revealed the existence of endogenic rhythms in protein synthesis with certain secretion plasticity within pancreacytes.
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PMID:[Rhythmic changes in protein synthesis in mouse pancreatocytes after food stimulation, in alloxan diabetes and in isoproterenol exposure]. 185 54

The involvement of Zn2+ in the inhibitory action of insulin and phenformin on bulk proteolysis was studied in the Langendorff rat heart with a Zn(2+)-buffering perfusate (0.1 mM citrate, physiological complete amino acids and 0.2% albumin). Proteins were biosynthetically labeled in vitro for 10 min with [3H]leucine. Rapidly degraded proteins were eliminated during a 3-h preliminary degradation without insulin or added Zn2+ (2 mM nonradioactive leucine). Insulin (5 nM), the lysosomal inhibitor chloroquine (30 microM), and the biguanide antihyperglycemic agent phenformin (2 microns) each caused a sustained 35-40% inhibition of [3H]leucine release beginning within 1-2 min and reaching a maximum at 1-1.5 h. When these agents were combined, their simultaneous proteolytic inhibitory effects were not appreciably greater than the effect of chloroquine alone. Infusion of supraphysiological perfusate Zn2+ (greater than 15 microM) mimicked the inhibitory effect of insulin and chloroquine on lysosomal proteolysis. Infusion of supraphysiological Co2+, Mn2+, Fe2+, and Cr3+ (30 microM, 0.5 h) caused no change in proteolysis; however, 30 microM Cu2+ caused a slight inhibition. Presumptive chelation of the background (approximately 20 nM) Zn2+ by infusion of 3 microM CaNa2 EDTA caused no change in protein degradation over 1-2 h. The infusion of a physiological concentration of 1 or 5 microM Zn2+ (as ZnCl2) caused no change in protein degradation over 1-2 h. Biguanides are known to reversibly form a Zn2+ complex with affinity less than that of Zn2+ for EDTA. Prior infusion of 3 microM CaNa2 EDTA inactivated the proteolytic inhibitory effect of maximal (2 microM) phenformin over at least 1.25 h of concurrent infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 May
PMID:Effect of Zn2+ on the proteolytic inhibitory action of insulin and biguanide antihyperglycemic drugs. 190 28

Plasma and urinary concentrations of different amino acids were investigated during diabetic ketoacidosis (DKA) and 12, 24, 72 hours after initiation of therapy. In DKA, plasma concentration of glutamic acid, aspartic acid, valine, leucine and isoleucine significantly increased while that of asparagine and glutamine decreased compared to levels in well-controlled diabetic patients. The urinary excretion of branched-chain amino acids, histidine, serine and threonine was elevated while those of glutamic acid, glutamine, glycine and taurine were reduced. Among the different amino acids, histidine excretion had the highest variability. A strong correlation was found between the urinary excretion of several amino acids and that of the beta-2-microglobulin characterizing tubular dysfunction. Changes in the excretion of different amino acids reflect the altered metabolic state and renal function due to DKA.
Diabetes Res Clin Pract 1991 May
PMID:Changes in plasma and urinary amino acid levels during diabetic ketoacidosis in children. 190 67

Tubulointerstitial lesions often develop in the kidneys of patients and experimental animals with diabetes mellitus. In an in vitro model of diabetic renal disease, it has been previously demonstrated in this laboratory that elevated glucose levels stimulate procollagen transcription and secretion in proximal tubule cells in culture while inducing cellular hypertrophy and reducing cellular proliferation. Previous experiments in other tissues have suggested that myo-inositol supplementation, probably by reversing a disturbance in cell myo-inositol metabolism related to increased activity of the polyol pathway, reverses the effects of glucose on cell function. We tested the effect of myo-inositol supplementation on proximal tubule cells in culture in the presence of elevated medium glucose level. Incubation in 450 mg/dL of glucose media reduced cell proliferation; 450 mg/dL of glucose plus myo-inositol (800 microM) increased proliferation, returning the value to that seen in cells incubated in 100 mg/dL of glucose. Incubation in 450 mg/dL of glucose media increased type IV and type I procollagen mRNA levels and peptide secretion rates compared with those seen in cells incubated in medium containing 100 mg/dL of glucose. This glucose-induced stimulation of procollagen mRNA levels and procollagen secretion was not observed when the elevated glucose medium was supplemented with 800 microM myo-inositol. On the other hand, myo-inositol supplementation did not prevent the glucose-induced cellular hypertrophy: there was no reduction in the increased leucine incorporation and cellular protein content. Cell incubation in 450 mg/dL of glucose media did not lead to a measurable decrease in total cellular myo-inositol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of myo-inositol on cell proliferation and collagen transcription and secretion in proximal tubule cells cultured in elevated glucose. 193 34

Abnormalities in proteoglycan metabolism have been implicated in the pathogenesis of diabetic nephropathy. Whether hyperglycemia plays a direct role in these events is unknown. To evaluate the effects of high glucose concentrations and insulinlike growth factor I (IGF-I) on kidney proteoglycan and protein metabolism, we incubated quiescent, subconfluent human fetal mesangial cells for 24 h in serum-free media containing either physiological (5.6-mM) or elevated (25-mM) glucose concentrations with or without 1.3 x 10(-9) M IGF-I. In the presence of physiological glucose concentrations, IGF-I stimulated incorporation of [3H]leucine into protein and [35S]sulfate or [3H]glucosamine into proteoglycans. High glucose concentrations significantly amplified IGF-I-mediated stimulation of protein synthesis but totally abolished IGF-I-induced proteoglycan synthesis. The hydrodynamic size and proportions of heparan-35SO4 and chondroitin/dermatan-35SO4 proteoglycans in all experimental media were the same. However, high glucose concentrations decreased the iduronic acid content of dermatan-35SO4. In separate experiments, quiescent cells were cultured for 7 days in media supplemented with 2% fetal calf serum. IGF-I had no effect on mesangial cell proliferation, but as cells reached confluence, high glucose concentrations significantly inhibited cell proliferation. This inhibition was not mimicked by isosmolar concentrations of mannitol. After 7 days, uptake of radioactive precursors into proteoglycans and proteins over 24 h was similar under all culture conditions. However, IGF-I decreased the ratio of [35S]sulfate to [3H]glucosamine in proteoglycans and their glycosaminoglycan side chains. This difference persisted in disaccharides derived by chondroitin ABC lyase digestion of dermatan-35SO4.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Oct
PMID:Effects of IGF-I and glucose on protein and proteoglycan synthesis by human fetal mesangial cells in culture. 193 96


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