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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The highest risk for the development of type I diabetes resides with first-degree relatives of the diabetic proband, this risk being in the order of 2.9%, 6.6% and 4.9% for parents, siblings and children of the proband, respectively. The major genetic markers associated with the development of insulin-dependent diabetes mellitus (IDDM) is the possession of the HLA alleles DR3/DR4 and more recently the absence of aspartate in the 57th position on the beta-chain of the HLA DQ gene (HLA DQ beta Asp 57 negative). The most important auto-immune marker for predicting preclinical IDDM is the presence of high titres (greater than 40 Juvenile Diabetes Foundation units) of islet cell antibodies (ICA), while the finding of insulin auto-antibodies (IAA) is a good predictive marker in children less than 5 years of age. The presence in a susceptible individual of ICA plus IAA is a better predictor of impending IDDM than the presence of either of these two markers alone. Antibodies which precipitate an islet membrane protein (MW 64K) are highly sensitive and specific markers of preclinical IDDM. The presence of 64K antibodies may well be the most important predictive marker of impending IDDM in the future. The progressive decline of the first phase of insulin secretion in response to an intravenous glucose challenge is associated with the onset of IDDM within 18 months. Of the immunotherapeutic agents at present used in clinically manifest IDDM, azathioprine has been shown to be ineffective in increasing the remission phase, while the value of nicotinamide is controversial.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Can we predict and/or prevent type I diabetes? 221 82

Rats with streptozotocin-induced diabetes of 10 weeks' duration showed significant changes in the total content of somatostatin, substance P and vasoactive intestinal polypeptide in the stomach and small intestine compared with control animals. An increase (p less than 0.05) in the concentration and total content of gastric somatostatin and a decrease (p less than 0.05) in the concentration and content of gastric substance P were seen in the streptozotocin-treated rats. The increase in the vasoactive intestinal polypeptide (VIP) content (54%, p less than 0.05) and the decrease in the substance P content (35%, p less than 0.05) of the gut may contribute to the impaired intestinal motility observed in animals with experimentally produced diabetes. Both the diabetogenic effect of streptozotocin and the changes in regulatory peptide concentrations were prevented by injection of nicotinamide before streptozotocin suggesting that the changes did not arise from a non-specific toxic effect of streptozotocin upon gastrointestinal neurones and/or endocrine cells.
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PMID:Changes in the somatostatin, substance P and vasoactive intestinal polypeptide content of the gastrointestinal tract following streptozotocin-induced diabetes in the rat. 241 23

Changes in the tissue content of phosphoribosyl pyrophosphate (PPRibP), glucose 6-phosphate, ribose 5-phosphate (Rib5P), RNA and DNA, of the activity of PPRibP synthetase (EC 2.7.6.1) and the conversion of [1-14C]- and [6-14C]-glucose into 14CO2 were measured at mid-lactation in the normal and diabetic rat and in pregnancy, lactation and mammary involution in the normal rat. The PPRibP, glucose 6-phosphate and Rib5P contents increase during pregnancy and early lactation to reach a plateau value at mid-lactation, before falling sharply during weaning. The PPRibP content, PPRibP synthetase activity and flux of glucose through the oxidative pentose phosphate pathway (PPP) all change in parallel during the lactation cycle. Similarly, after 3 and 5 days duration of streptozotocin-induced diabetes, ending on day 10 of lactation, there were parallel declines in PPRibP content, PPRibP synthetase and PPP activity. The effect of streptozotocin was prevented by pretreatment with nicotinamide and partially reversed by insulin administration. Addition of insulin to lactating rat mammary-gland slices incubated in vitro significantly raised the PPRibP content (+47%) and the activity of the PPP (+40%); phenazine methosulphate, which gives a 2-fold increase in PPP activity, raised the PPRibP content of lactating mammary gland slices by approx. 3-fold. It is concluded that Rib5P, generated in the oxidative segment of the PPP, is an important determinant of PPRibP synthesis in the lactating rat mammary gland and that insulin plays a central role in the regulation of the bioavailability of this precursor of nucleotide and nucleic acid synthesis.
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PMID:Phosphoribosyl pyrophosphate and phosphoribosyl pyrophosphate synthetase in rat mammary gland. Changes in the lactation cycle and effects of diabetes, insulin and phenazine methosulphate. 243 83

Human fetal pancreas (HFP) is a potential source of beta-cells for transplantation to insulin-dependent diabetic patients. We have previously described a method for tissue culture of HFP that results in the in vitro development of isletlike cell clusters (ICCs) containing a minority of insulin-positive cells. Recently we found that nicotinamide, an inhibitor of poly(ADP-ribose) synthetase, induces an increased islet cell DNA replication both in vivo and in vitro. In this study, this culture technique was used to evaluate the effects of addition of 10 mM nicotinamide on HFP explants cultured in RPMI-1640 medium plus 10% human serum. ICCs developed in 11 of 19 consecutive cultures with nicotinamide increased the yield of ICCs by 40%. Also, the insulin content of ICCs increased approximately 50% with nicotinamide supplementation, although measurements of DNA indicated an unchanged number of cells in each ICC. Neither the rates of insulin release in response to 16.7 mM glucose plus 5 mM theophylline nor the (pro)insulin or total protein biosynthesis rates were affected by nicotinamide addition. The combined results of this study suggest that nicotinamide is useful for stimulating the formation of ICCs from HFP.
Diabetes 1989 Jan
PMID:Tissue culture of human fetal pancreas. Effects of nicotinamide on insulin production and formation of isletlike cell clusters. 252 29

We examined the effects of desferrioxamine (DFX), a potent inhibitor of the formation of oxygen-derived hydroxyl radicals, and nicotinamide (NIC), a poly(ADP-ribose) synthetase inhibitor and a weak free-radical scavenger, on two models of immune destruction of murine islets [i.e., allograft rejection and multiple low-dose streptozocin (STZ)-induced insulitis]. Freshly isolated or low-temperature-cultured BALB/cJ islets were transplanted beneath the kidney capsules of C57BL/6J recipients. The recipients were treated with NIC alone (500 mg.kg-1.day-1), DFX alone (4.2 mg/day x 14 days), or NIC + DFX. Only recipients treated with NIC + DFX, receiving cultured islets, showed a mean graft survival time significantly longer than control mice receiving freshly isolated or cultured islets. Control CD-1 mice treated with multiple low doses of STZ developed insulitis and diabetes. Treatment with NIC alone, DFX alone, or NIC + DFX decreased the severity of hyperglycemia relative to the controls. Treatment with DFX alone was more effective than NIC alone or NIC + DFX. Only the group treated with DFX alone had a lower incidence of diabetes (mean plasma glucose level greater than 200 mg/dl) than the controls after 4 wk. Histologically, islets from control mice showed severe insulitis, islet destruction, and absence of stainable insulin, whereas islets from DFX-treated mice showed only mild peri-insulitis and a relative preservation of beta-cell granulation. Our study showed that NIC and DFX partially protect islets from immune destruction in allograft rejection and in low-dose STZ-induced insulitis. Apparently, hydroxyl radicals play important roles in both of these models.
Diabetes 1989 Mar
PMID:Oxygen free-radical scavengers and immune destruction of murine islets in allograft rejection and multiple low-dose streptozocin-induced insulitis. 252 36

The effect of insulin-dependent diabetes on the hepatic microsomal activation of chemical carcinogens to mutagenic intermediates in the Ames test was investigated in rats pretreated with streptozotocin. In order to discern between the effects of streptozotocin itself and that of the resulting diabetes, groups of streptozotocin-treated rats received either nicotinamide simultaneously with the diabetogenic agent to prevent the onset of diabetes or daily treatment with insulin in order to antagonise the effects of diabetes. The activation of two nitrosamines, nitrosopiperidine and nitrosopyrrolidine was markedly increased following treatment of the animals with streptozotocin, the effect being preventable by nicotinamide and effectively antagonised by insulin. A similar increase in mutagenic response was also seen when Glu-P-1, a carcinogen generated during the cooking of proteinaceous food, was employed as the mutagen. In contrast, the diabetic rats were less efficient than control animals in activating the aromatic amine 2-aminofluorene to mutagenic intermediates. Concomitant administration of nicotinamide with streptozotocin prevented the decrease in mutagenicity, and daily treatment of diabetic rats with insulin partially restored mutagenic response to control levels. Streptozotocin-induced diabetes had no effect on the mutagenicity of 4-aminobiphenyl and the two polycyclic aromatic hydrocarbons, benzo(a)pyrene and 3-methylcholanthrene. The present findings clearly illustrate that diabetes modulates the metabolic activation of carcinogenic chemicals, the effect being dependent on the nature of the carcinogen.
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PMID:Metabolic activation of chemical carcinogens by hepatic preparations from streptozotocin-treated rats. 252 16

This study describes the effects of nicotinamide therapy on B-cell function in Type 1 (insulin-dependent) diabetes. C-peptide secretion was studied in 20 patients newly diagnosed with Type 1 diabetes at basal state and also after an i.v. glucagon stimulus. Patients were randomly allocated according to a single-blind schedule, to one of the following treatments over a 45-day period: Group 1: 10 patients, nicotinamide 1 g/day; Group 2: 10 patients, placebo. The C-peptide secretion tests were performed before treatment and on days 15, 45, 180, 365 of the follow-up. The clinical and metabolic data were similar in the two groups of patients. Basal and stimulated C-peptide levels increased by 45 days in both groups, but the increase in stimulated C-peptide response was greater in the nicotinamide group (p less than 0.01). However, the B-cell function decreased after the period of nicotinamide administration. No difference in the number of clinical remissions or insulin requirement and HbA1 between the groups was observed. These data suggest that treatment of Type 1 diabetes with nicotinamide at diagnosis is associated with a moderate increase of C-peptide secretion recovery.
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PMID:Effect of nicotinamide therapy upon B-cell function in newly diagnosed type 1 (insulin-dependent) diabetic patients. 252 67

In vivo and in vitro experiments have shown that nicotinamide enhances the regeneration of rat B cells. Nicotinamide has been administered to human subjects at a dose of 3 g/day for more than one year without any serious side effects. A trial was conducted to study if nicotinamide could protect B cells in Type I (insulin-dependent) diabetic patients with established diabetes, but still with residual insulin secretion, the latter being evaluated throughout the study period. A randomized double-blind study was carried out on 26 Type I diabetic patients aged 15 to 40 years who had been treated with insulin for 1 to 5 years but who had a residual insulin secretion characterized by a glucagon stimulated C-peptide level higher than 0.1 nmol/l. They were given either 3 g/day of nicotinamide or a placebo for nine months. At baseline the treated and control groups did not differ according to age, diabetes duration, insulin dose, HbA1c or C-peptide levels. Three patients dropped out of the study. At 9 months there were no significant changes in the insulin doses required. However, HbA1c rose in the control group (8.1 +/- 0.4 vs 9.8 +/- 0.5%, p less than 0.05) but not in the nicotinamide treated group (7.5 +/- 0.5 vs 6.9 +/- 0.4%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nicotinamide treatment on the residual insulin secretion in type 1 (insulin-dependent) diabetic patients. 252 69

Nicotinamide, a poly-(ADP-ribose) synthetase inhibitor, has been shown in animal models to induce islet B-cell regeneration. An open controlled trial was therefore carried out for 1 year in 36 patients with recent onset (less than 4 weeks symptoms) Type 1 diabetes. Twenty-three patients were treated with nicotinamide (200 mg daily) in addition to insulin, and 13 control patients were treated with insulin alone. Metabolic and immunological variables at entry were similar in the two groups. A significant increase of stimulated plasma C-peptide levels compared to diagnosis was observed only in the nicotinamide treated group (1.4 +/- 0.3 (+/- SE) micrograms l-1 at diagnosis vs 2.4 +/- 0.4 at 6 months, p less than 0.04; and 3.0 +/- 0.5 at 1 year, p less than 0.01). Patients receiving nicotinamide had lower glycosylated haemoglobin levels at 6 months and 1 year compared to the control group (p less than 0.04 and p less than 0.03, respectively) although insulin dose was lower. Small doses of nicotinamide may be successful in improving metabolic control in recent onset Type 1 diabetes, probably by increasing residual islet B-cell function.
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PMID:Nicotinamide increases C-peptide secretion in patients with recent onset type 1 diabetes. 252 94

Rats injected i.p. with a single dose of nicotinamide (250 mg/kg) 15 min prior to i.v. injection of streptozotocin (65 mg/kg) develop a very mild form of diabetes characterized by slight elevations of plasma glucose, increased levels of HbA1, and reduced insulin secretion in response to an i.v. glucose tolerance test. These rats gain weight normally and they are not hyperphagic, glycosuric, or polyuric. The effects of this very mild form of diabetes vs overt streptozotocin diabetes of three months duration on regional vascular 131I-albumin clearance, blood flow (assessed by 15 microns 85Sr-microspheres), and renal filtration function were examined in male Sprague-Dawley rats. Plasma glucose levels of rats with mild diabetes were 7.4 +/- 0.9 (mean +/- SD) (mmol/l) vs 6.5 +/- 0.6 for control rats and 31.3 +/- 6.0 for overtly diabetic rats. HbA1 levels were increased 1.4 fold in mildly diabetic and 2.3 fold in overtly diabetic rats. Vascular clearance of 131I-albumin was markedly increased in ocular tissues (anterior uvea, retina, and choroid), sciatic nerve, aorta, new (subcutaneous) granulation tissue, and kidney of both diabetic groups, although increases in overtly diabetic rats exceeded those in the mildly diabetic group (2.2-4.6 times control animals vs 1.6-3.3 times, respectively). Likewise, both overt and very mild diabetes markedly increased glomerular filtration rate (approximately 1.8 times and 1.2 times control animals, respectively), urinary excretion of endogenous albumin (approximately 9 times and 4 times) and IgG (approximately 15 times and 4 times), as well as regional blood flow in the anterior uvea, choroid, and sciatic nerve. Increases in tissue sorbitol levels were much larger in overtly diabetic rats (generally 10-20 times control animals) than in mildly diabetic rats (1.5-3 times controls). myo-Inositol levels were significantly decreased only in lens and sciatic nerve of overtly diabetic rats. These observations indicate that even very mild diabetes is associated with vascular functional changes which develop more slowly than in overtly diabetic rats, but are disproportionately large (in view of the minimal increases in glycaemia and tissue polyol levels) compared to those in overtly diabetic rats.
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PMID:Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats. 253 17


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