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)

Oral administration of foreign proteins, e.g. cow's milk (CM) proteins, stimulates the immune system and induces humoral and cellular immune response against these antigens in infants. Up-regulation of adhesion molecules is known to be associated with activation of the immune system. The purpose of the study was to examine whether orally administered CM proteins induce elevation in soluble adhesion molecules, i.e. intercellular adhesion molecule-1 (ICAM-1) and L-selectin, in infants. In a double-blind trial, 10 infants received CM-based formula and 10 infants casein hydrolysate formula until the age of 9 mo. The infants of mothers with insulin-dependent diabetes mellitus (IDDM) were recruited into a pilot study of a trial for primary prevention of IDDM by elimination of CM proteins from the diet during early infancy. A cord blood sample and peripheral blood samples were taken at the ages of 3, 6, 9, and 12 mo of age. The levels of soluble ICAM-1 and L-selectin were measured by ELISA. The levels of soluble ICAM-1 were higher at the ages of 3, 6, 9, and 12 mo in infants who received CM-based formula than in infants who received hydrolyzed formula (p = 0.05). Instead, no difference was found in the the levels of soluble L-selectin. The levels of soluble ICAM-1 and L-selectin were higher in all infants when compared with the levels reported in adults or to the levels seen in cord blood. Orally fed CM proteins induce an elevation in soluble ICAM-1 in infants. This may reflect the generation of an immune response against these proteins, because ICAM-1 has an important costimulatory role in lymphocyte activation.
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PMID:Soluble adhesion molecules and oral antigen feeding in infants. 882 77

We studied 20 infants of mothers with IDDM participating in a pilot study for a dietary intervention trial, testing the hypothesis that avoidance of cow's milk proteins early in life will reduce the risk of subsequent IDDM. The aim was to evaluate the elimination of IDDM-associated antibodies from the peripheral circulation of the infants, the possible emergence of autoantibodies indicating beta-cell destruction, and the influence of the dietary intervention and genetic disease susceptibility on the development of these autoantibodies. Transplacentally transferred islet cell antibodies (ICAs) and antibodies to the 65-kDa isoform of glutamic acid decarboxylase (GAD65As) disappeared from the peripheral circulation of most infants over the first few months of life and in all infants before the age of 9 months. Insulin antibodies were eliminated before the same age in all cases but one. The higher the initial antibody level was, the longer the time required for elimination. Four infants tested positive for insulin autoantibodies (IAAs) on at least one occasion during the first year of life, and 5 out of 16 unaffected subjects (31%) had IAAs at the age of 2 years. One infant became positive for IAA before the age of 6 months, with increasing levels later, seroconverted to positivity for ICAs and GAD65As between 6 and 9 months and presented with clinical IDDM at the age of 14 months. He had the HLA DQB1*0302/x genotype, which predisposes carriers to IDDM, and had been given the casein hydrolysate formula as supplementary milk. There were no significant differences in the levels of various autoantibodies between two groups of subjects defined either on the type of dietary intervention or the degree of genetic susceptibility. The findings indicate that transplacentally transferred antibodies related to IDDM are usually eliminated from the peripheral circulation of infants before 9 months of age and that IDDM-associated autoantibodies may emerge before the age of 6 months. Our results also illustrate that avoidance of cow's milk proteins over the first 9 months of life does not provide total protection against IDDM.
Diabetes 1996 Dec
PMID:Disease-associated antibodies in offspring of mothers with IDDM. 892 55

Clinical as well as experimental studies in insulinopenic diabetes mellitus have demonstrated abnormal pancreatic exocrine responses to cholecystokinin (CCK). In the present study, we examined pancreatic exocrine and endocrine function in the recently developed genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and compared them with those in the control Long-Evans Tokushima Otsuka (LETO) rats of the same age. Stepwise increasing doses of CCK octapeptide (CCK-8; 0.027-7.0 nmol.kg-1.h-1) evoked a characteristic biphasic dose-response curve for pancreatic juice and protein output in the LETO rats, whereas the OLETF rats were totally insensitive to CCK-8 stimulation. However, the responsiveness and the sensitivity to both carbamylcholine and secretin were similar in the two groups. Intraduodenal infusion of casein (500 mg/h) failed to stimulate pancreatic exocrine secretion in the OLETF rats despite a greater CCK response than in the LETO rats (peak response: 8.43 +/- 0.97 vs 5.12 +/- 0.30 pmol/l in LETO, P < 0.01). Intravenous infusion of CCK-8 (4.4 nmol.kg-1.20 min-1) caused a significant increase in serum insulin concentrations and a concomitant decrease in glucose levels in the LETO rats but not in the OLETF rats. On the other hand, an intravenous bolus injection of 1.1 mmol/kg glucose caused a greater insulin release in the OLETF rats than in the LETO rats. In contrast, gastric acid secretion in the OLETF rats was significantly high in basal and in response to intravenous infusion of CCK-8 compared with that in the LETO rats. Four subcutaneous injections of 20 micrograms/kg caerulein at hourly intervals over 3 h induced acute pancreatitis in the LETO rats but did not elicit any significant increase in serum amylase or lipase activities and pancreatic wet weight or histological evidence of acute pancreatitis in the OLETF rats. These results indicate that the exocrine and endocrine pancreas of the recently developed genetically diabetic OLETF rats are totally and specifically insensitive to exogenous and endogenous CCK stimulation, whereas parietal cells in these rats are sensitive to CCK stimulation.
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PMID:Defect in pancreatic exocrine and endocrine response to CCK in genetically diabetic OLETF rats. 892 5

We postulated whether interventions capable of restoring euglycemia would correct whole-body protein metabolism, shown previously to be elevated in hyperglycemic persons with non-insulin-dependent diabetes (NIDDM). The kinetics of protein metabolism were estimated in obese subjects with NIDDM in the hyper- and normoglycemic states during isoenergetic feeding and in the normoglycemic state induced by 4 wk of a very-low-energy diet (VLED) with constant protein intake. Seven NIDDM subjects [three males and four females with a body mass index (in kg/m2) of 39 +/- 2] were given a weight-maintaining, liquid formula providing 95 g protein/d for 15 d, followed in six subjects (two males and four females) for 27 d by a diet providing 1.7 MJ, 93 g protein derived from casein-soy, 13 g carbohydrate, 2 g fat, multivitamins and minerals, and a potassium bicarbonate supplement (32 mmol) per day. Exogenous insulin was given to achieve normoglycemia during the first 8 d of isoenergetic feeding. On days 6-8, 12-14, and 25-27, nitrogen flux rate was calculated from the urine [15N]urea enrichment by using the 60-h oral [15N]glycine method to obtain "integrated" feeding and fasting values. Rates of synthesis and breakdown were calculated from nitrogen flux. During isoenergetic feeding, normoglycemia was associated with more positive nitrogen balance (2.6 +/- 0.5 compared with -0.6 +/- 0.6 g N/d, P < 0.05); 18-23% lower nitrogen flux, and synthesis and breakdown rates (P < 0.05), and a 3% decrease in resting energy expenditure (P < 0.05). During the VLED, euglycemia was achieved but nitrogen balance, although it became less negative with time, never reached equilibrium. This was associated with significant (P < 0.05) decreases in the synthesis rate, resulting in net protein losses. Thus, the altered protein metabolism in moderately hyperglycemic NIDDM subjects was improved with exogenous insulin in doses sufficient to restore normoglycemia in the isoenergetic fed state, but it remained abnormal with a reduced non-protein energy intake. This suggests that protein metabolism is more sensitive to insulinization than was thought previously.
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PMID:Effect of glycemic control on the kinetics of whole-body protein metabolism in obese subjects with non-insulin-dependent diabetes mellitus during iso- and hypoenergetic feeding. 906 41

Human epidemiological studies delineated early exposure to intact dietary protein (e.g., most infant formulas) as an environmental risk factor for the development of IDDM. The Trial to Reduce IDDM in the Genetically at Risk (TRIGR), an international IDDM prevention trial, has been designed to determine if avoidance of intact dairy protein in high-risk infants < or =6 months of age can reduce the subsequent diabetes incidence. We here studied the casein hydrolysate-based trial diet (Nutramigen) in NOD mice. When given either continuously or for 10 weeks after weaning, the test diet was highly effective in preventing autoimmune diabetes (32-week incidence: 4.6 vs. 58.8%) and in preserving pancreatic insulin levels, with little effect on islet inflammation. Spleen cells from protected NOD mice failed to adoptively transfer diabetes into irradiated syngeneic recipients. When co-transferred with splenocytes from diabetic donors, cells from diet-protected mice inhibited adoptive diabetes transfer (incidence 50 vs. 94%, P < 0.001). T-cell reactivity to the islet cell autoantigens ICA69 (islet cell antigen 69) and GAD65 developed only in diabetic recipients of spleen cell grafts, indicating that diabetes protection extends to more than one autoantigen. In protected mice, ICA69 T-cell reactivity was not detectable spontaneously nor after priming with this autoantigen; however, priming with the cross-reactive non-self-antigen bovine serum albumin recruited T-cells responsive to ICA69. Thus, diabetes prevention with the clinical trial diet is effective in NOD mice, where it affects some T-cell repertoires and allows development of regulatory cells that interfere with destructive autoimmunity.
Diabetes 1997 Apr
PMID:Immunological aspects of nutritional diabetes prevention in NOD mice: a pilot study for the cow's milk-based IDDM prevention trial. 907 94

Certain diets can have major effects on the development of IDDM in DP-BB rats, but data are scant on the timing, dose, and mechanisms involved. We therefore determined the dose response, timing, and duration of exposure required to induce diabetes, and characterized the effects of nutritionally adequate diets with widely different diabetogenicity on the pancreatic islet area and cytokines. DP-BB rats were fed a diabetogenic, cereal-based, NIH-07 (NIH) diet or a protective, casein or hydrolyzed casein (HC)-based, semipurified diet. Rats were fed from weaning to 50 or 100 days with the HC diet and then switched to the NIH diet, or fed the NIH diet from weaning to 50 days and switched to the HC diet. Pancreas histology and diabetes outcome were determined. Semiquantitative morphometric analyses of hematoxylin and eosin-stained sections of pancreas from 41-day-old rats were also carried out. Diet-induced effects on pancreatic cytokine levels were measured at 70 days using reverse transcriptase-polymerase chain reaction analysis of gamma-interferon (IFN-gamma), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta). Long-term daily exposure, particularly around the beginning of puberty to late adolescence (50-100 days), was important for development of diabetes. DP-BB rats could be rescued from diabetes development by feeding them a low-diabetogen HC diet as late as 50 days. Diabetes frequency was highest in rats fed 70% and 100% NIH diets. By age 41 days, before classic insulitis, the islet area in HC-fed DP-BB rats was 65% greater than in NIH-fed rats. By 70 days, when mononuclear cells were visible in the islets of most NIH-fed, but not HC-fed rats, the more pronounced inflammatory process in NIH-fed rats was associated with a Th1 cytokine pattern (high IFN-gamma and low IL-10 and TGF-beta), whereas the pancreases of HC-fed rats showed fewer infiltrating cells, low levels of IFN-gamma, and high levels of TGF-beta, typical of a Th2 cytokine pattern. Thus dietary modification can occur as late as puberty. Further, long-term exposure to sufficient amounts of food diabetogens between 50 and 100 days was required for maximum diabetes induction. The islet area was modified by diet before signs of classic insulitis. Pancreatic inflammation in NIH-fed animals is a Th1-dependent phenomenon. The HC diet inhibited insulitis and was associated with a Th2 cytokine pattern in the pancreas, protecting diabetes-prone rats from developing diabetes.
Diabetes 1997 Apr
PMID:Potential mechanisms by which certain foods promote or inhibit the development of spontaneous diabetes in BB rats: dose, timing, early effect on islet area, and switch in infiltrate from Th1 to Th2 cells. 907 98

To investigate the effects of different dietary fatty acids and proteins on glucose tolerance and insulin receptor gene expression, Wistar fatty rats (genetically obese, noninsulin-dependent diabetes mellitus) and their lean littermates (8 wk old) were fed a casein or soybean protein diet containing 9% partially saturated beef tallow (plus 1% corn oil), 10% corn oil or 10% fish oil for 3 wk. In glucose tolerance tests, plasma insulin concentrations were significantly higher in obese rats fed corn oil or fish oil than in those fed partially saturated beef tallow, particularly in the soybean protein groups. However, plasma glucose concentrations were not significantly affected by dietary protein or fat. The insulin receptor mRNA concentrations in livers and adipose tissues were higher in rats fed soybean protein/partially saturated beef tallow than in those fed any other protein/fat combination. Dietary soybean protein may help to reduce the insulin resistance, but only when a diet low in polyunsaturated fatty acids is consumed. On the other hand, the insulin receptor mRNA concentrations in adipose tissue were generally lower in the obese rats of all dietary groups than in the lean rats, suggesting that insulin resistance may be due to a defect of insulin receptor gene expression.
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PMID:Dietary soybean protein increases insulin receptor gene expression in Wistar fatty rats when dietary polyunsaturated fatty acid level is low. 918 20

One theory of the pathogenesis of IDDM proposes that exposure to cow's milk proteins triggers the disease in genetically susceptible individuals. We tested this hypothesis in the BB/Wor rat model of human IDDM. Diabetes-prone (DP) BB/Wor rats spontaneously develop IDDM. Coisogenic diabetes-resistant (DR) BB/Wor rats do not develop diabetes spontaneously, but IDDM can readily be induced by treatment with polyinosinic:polycytidylic acid and depletion of RT6+ T-cells. Pregnant BB/Wor rats were fed one of four experimental diets or a standard Purina commercial rat chow (5010) that was certified to be free of cow's milk protein. Offspring were maintained on the maternal diet after weaning. DP-BB/Wor rats, fed either of two experimental diets based on hydrolyzed casein and free of intact milk protein (Nutramigen or D11236), developed diabetes at only half the rate of animals fed Purina 5010 chow. Neither the addition of bovine serum albumin (BSA) to Nutramigen nor the substitution of total milk protein for the hydrolyzed casein in the D11236 diet increased the frequency of spontaneous diabetes. In contrast, there was no relationship between diet and susceptibility of DR-BB/Wor rats to IDDM induction. However, the methods used to induce IDDM in DR-BB/Wor animals were found to induce antibodies against BSA. We conclude the following: 1) Dietary modification can reduce spontaneous IDDM expression in DP-BB/Wor rats, but the agent of protection is not elimination of cow's milk protein. 2) The addition of BSA or intact milk protein does not abrogate the effectiveness of a protective diet. 3) The genetic susceptibility of the DR-BB/Wor rat to autoimmune diabetes is unaffected by any of the tested diets, but a role of anti-BSA-like autoreactivity in IDDM expression cannot be excluded.
Diabetes 1997 Jul
PMID:Dietary cow's milk protein does not alter the frequency of diabetes in the BB rat. 920 Jun 47

Exposure to cow milk (CM)-based formulas in early infancy has been associated with an increased risk of insulin-dependent diabetes mellitus (IDDM), but studies on the possible pathogenic mechanism(s) linking CM and IDDM are contradicting. We hypothesized that if CM formulas contained bovine insulin (BI), exposure to them could lead to immunization against insulin, which is the only known beta-cell-specific autoantigen in IDDM. We measured immunoglobulin G (IgG) antibodies by enzyme immunoassay (EIA) to BI and human insulin (HI) in children who received, during the first 9 months of life, either a formula containing whole CM proteins or a formula containing hydrolyzed casein (HC) peptides. BI was detectable by radioimmunoassay (RIA) and immunoblotting in the CM-based formula. At 6 months of age the children who received CM formula had higher levels of IgG antibodies to BI than children who received either HC formula or children who were exclusively breast-fed (median levels 0.480 versus 0.185, P = 0.04; and 0.480 versus 0.160, P = 0.04; respectively). Also, at 9 months of age, children in the CM group differed from the HC group (0.403 versus 0.230; P = 0.02). Antibodies to BI and HI showed a positive correlation and cross-reacted in inhibition studies. The high incidence of insulin-binding antibodies in young children with IDDM may be explained by oral immunization to BI present in CM. Exposure to BI, which differs from HI only by three amino acids, may break the tolerance to insulin.
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PMID:Cow milk feeding induces antibodies to insulin in children--a link between cow milk and insulin-dependent diabetes mellitus? 949 88

Diet is an important factor influencing the development of diabetes in the Biobreeding (BB) rat. Changes in gut development and absorption of nutrients in the diabetes-prone rat (Bbdp) and the subsequent effect on pancreatic function may play a role in the ultimate development of the disease. BBdp and normal (BBn) dams were fed one of three diets, chow or semipurified diets containing either soy or casein as the protein source. Pups were weaned at 21 d onto the same diet as their respective dam and killed at 30 d. Chow-fed BBn animals weighed significantly more than casein- or soy-fed BBn animals. Chow-fed BBdp had significantly greater small intestine and colon weight when expressed on a per body weight basis than BBn. With all three diets, BBdp animals had significantly lower colonic proglucagon mRNA abundance than did BBn animals. Adjusting for total colonic RNA content resulted in only casein- and soy-fed BBdp animals demonstrating significantly lower colonic proglucagon mRNA abundance than did BBn animals. BBn animals had higher levels of sodium-dependent D-glucose cotransporter (SGLT)-1 and sodium-independent glucose transporter (GLUT) 5 mRNA than did BBdp. Within BBn animals, casein and soy produced significantly lower levels of SGLT-1 and GLUT5 mRNA than did chow. This study demonstrates that BBn and BBdp animals respond differently to chow versus semipurified weaning diets. These differences may explain the differences in growth and intestinal development among the BBdp and BBn strains weaned onto different diets.
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PMID:Proglucagon and glucose transporter mRNA is altered by diet and disease susceptibility in 30-day-old biobreeding (BB) diabetes-prone and normal rats. 966 73


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