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)

Diazoxide 5 mg/kg/day was administered to four normal subjects for five days and, together with insulin, to ten diabetic subjects for seven days. In every case there was a substantial increase in the insulin response to combined stimulation of the pancreatic beta cells with 1 mg of glucagon and 2 g of tolbutamide given intravenously. Similar increases were not seen in four diabetics who received placebo with insulin. It is likely that the observed improvements reflected increased insulin stores which resulted from diazoxide inhibition of insulin release. These findings suggest that poor insulin responses in diabetics may be due, at least in part, to chronic overstimulation of the beta cells. Pharmacological agents such as diazoxide, which inhibit glucose-induced insulin release, may have a place in preserving and restoring insulin secretion in diabetes.
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PMID:Improvement in insulin secretion in diabetes after diazoxide. 5 17

These studies suggest that the immunologic indicator in the radioimmune assay, 125I-iodoinsulin, selects antibody populations from within the antiserum that interact with determinants distant from the solvent surface on the insulin molecule to which iodine is substituted. Evidence is presented that the connecting peptide of proinsulin is in close proximity to regions on the solvent surface of the A-chain of insulin that include the tyrosyl residues at A-14 and A-19. A marked immunologic cross-reaction between derivatives of insulin with perturbations in the regions of tyrosyl A-14 and A-19 was noted in the radioimmune assay employing desalanine-(B-30)-desasparagine-(A-21)-insulin antiserum. This observation is consistent with the presence of a restricted population of antibodies in such antisera that is directed toward immunologic determinants in or near the insulin dimer site. The apparent immunologic activity of insulin derivatives depends on which antibody populations from the antiserum pool can react with the immunologic indicatory employed on the one hand and on the composition of antibodies in that antiserum on the other. These studies indicate that the specificity of antibody populations in a given antiserum can be identified and their levels quantitated with several assay systems, each employing one of a variety of indicators.
Diabetes 1976 May
PMID:Structural studies of insulin and insulin derivatives using various immunologic indicators and antibody populations. 5 91

To gain further insight into the genetic determinants of diabetic small vessel disease, we studied 22 HLA antigens in 110 juvenile-onset, insulin-dependent diabetics with terminal glomerulosclerosis and retinopathy, who were being prepared for kidney transplant. HLA antigens were comtemporarily determined in non-diabetic kidney transplant recipients and healthy controls. The frequency of antigens A1 and B8 were significantly higher in diabetics than in controls (P less than .02 and .011), but the frequency of BW15 was normal. The data are compatible with the concept that juvenile diabetes with microangiopathy is one of the HLA-B8 associated disorders.
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PMID:Histocompatibility (HLA) antigens and diabetic microangiopathy. 5 63

The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, alpah1-acid glycoprotein, alpha2-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 mug.) used was insufficient to induce synthesis of alpha2-acute phase globulin, net syntheses of albumin, fibrogen, alpha1-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and alpha1-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.
Diabetes 1976
PMID:Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins. 6 Nov 40

Autoantibodies reacting with discrete populations of cells in normal human pancreatic islets were found by immunofluorescence in 17 out of 1279 sera. A double immunofluorescence technique, with antisera to pancreatic glucagon, insulin, somatostatin, and human pancreatic polypeptide was used to show that 13 of the sera contained anitbodies reacting specifically with glucagon cells, while the other 4 reacted with somatostatin cells. These antibodies were directed against intracellular components and not against the hormones themselves. Both types of antibody occurred independently of the islet-cell antibodies which have been described in diabetes mellitus. These findings suggest selective damage to individual cell types in the pancreatic islets and raise the possibility of corresponding hormone deficiency syndromes.
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PMID:Separate autoantibodies to human pancreatic glucagon and somatostatin cells. 6 13

Pancreatic islet-cell antibodies (I.C.Ab) were detected in 31 patients with organ-specific autoimmune disorders, 4 first-degree relatives of I.C.Ab-positive diabetics, and 1 apparently normal subject, none of whom had clinical evidence of diabetes. 10 of these 36 subjects were found to have diabetic glucose-tolerance tests (G.T.T.S), 4 had lag storage, and 22 had normal G.T.T.S.2 had latent diabetes, as evidenced by diabetic G.T.T.S during pregnancy and thyrotoxicosis; another 2 subsequently developed insulin-dependent diabetes (I.D.D.) Serum from 26 subjects had been stored for 1-11 yr before the G.T.T.S were done. The titres in some were shown to rise and fall over the years, while in others they remained remarkably constant. There was no correlation between the titre, change in titre or the duration of I.C.Ab or the presence of HLA-B8, BW15, or CW3 and the result of the G.T.T. In addition to acting as a marker for asymptomatic and latent diabetes and prediabetes, it seems that the presence of I.C.Ab in the serum may define a new group of potential diabetics with normal G.T.T.S. Many such subjects have one or more organ-specific autoimmune disorders (irrespective of diabetic family history), but some are first-degree relatives of I.C.Ab-positive subjects (mainly I.D.D.). About 0-5% of the general population also have I.C.Ab in their serum.
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PMID:Pancreatic islet-cell antibody as a marker for asymptomatic and latent diabetes and prediabetes. 6 45

Infusion of somatostatin, an inhibitor of glucagon secretion, in insulin-dependent diabetics resulted in a 75-100% reduction in the blood-glucose rise after oral glucose administration, but did not improve intravenous glucose tolerance. Somatostatin reduced blood-xylose levels by 50-90% after ingestion of this pentose and delayed the peak increment in blood-xylose by 1-2 h. Similar effects on blood-xylose levels and a 30% reduction in splanchnic blood-flow were observed in normal subjects during infusion of somatostatin. Glucagon administration (3 ng per kg per min) or intraduodenal administration of xylose did not reverse somatostatin's effect on xylose tolerance. Somatostatin reduces postprandial hyperglycaemia in diabetes primarily by decreasing and/or delaying carbohydrate absorption rather than enhancing carbohydrate disposal. This effect may be mediated, in part, but a reduction in splanchnic blood-flow. These findings indicate that postprandial hyperglycaemia in diabetes is due primarily to insulin deficiency rather than glucagon excess.
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PMID:Influence of somatostatin on carbohydrate disposal and absorption in diabetes mellitus. 6 40

When guinea pig antibodies (ab) bind insulin (ag), they can make complexes of different sizes. We propose the following model: In ab excess: (see article) Intermediate: (see article) In ag excess: (see article). An insulin molecule acts as a bivalent antigen, although more than two different antigenic determinants may be present. In vivo the large C II type disappears more rapidly from the blood than does the C I. The C II binds to complement factor C1q, whilst C I and C III do not. In sera from insulin treated patients we found C I and C III. The lack of lattice formation, due to the bivalency, may explain the difficulty in obtaining precipitation. The different complexes may influence calculations of antibody concentrations and affinity constants of the binding sites. The in vivo effects and possible clinical effects of antibodies to insulin may depend on the type of complex formed. Possibly, prevailing C II formation tends to cause large insulin requirements, although C II may seldomly be detected in the blood, because of rappid trapping. The immune complexes could affect the progression of angiopathy a) by interfering with insulin metabolism and control of diabetes, and b) by complement activation (mainly C II) and trapping in the vascular bed.
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PMID:Insulin--anti-insulin complexes. 6 11

Islet-cell antibodies (I.C.A.) were found in 38% (319/829) of insulin-dependent diabetic patients, in 5% (6/112) of insulin-independent diabetics, and in 1.7% (3/177) of non-diabetic subjects. In the insulin-dependent group I.C.A. were found in 85% of patients immediately after the onset of symptoms and they became less common as the duration of disease increased I.C.A. were equally common in both sexes and the decline in their prevalence was independent of age. The antibodies were directed against cytoplasmic components of islet cells but not against insulin itself. The appearance of I.C.A. probably follows cell damage occurring before the onset of symptoms. By contrast, thyroid and gastric autoantibodies were more common in older patients and females. There was no correlation between the presence of these antibodies and I.C.A. in patients with either diabetes of recent onset or longstanding disease.
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PMID:Islet-cell antibodies in diabetes mellitus. 6 47

110 people in whom insulin-dependent diabetes developed when they were less than 30 years old were studied as soon as possible after diagnosis. There was evidence for clustering of cases with BW15-positive phenotypes during the winter peak (1976) but not during the autumn peak (1975). Subjects who were BW15-positive, and in particular those who were both B8 and BW15-positive, had higher neutralising antibody titres to Coxsackle virus types B1-B4 58% of cases had islet-cell antibodies (I.C.A.), but the presence of I.C.A. was not correlated with HLA phenotypes or viral antibody titres. In 41 subjects (37%), who gave a definite history of antecedent illness, evidence indicated that this was a precipitating infection and not the initiating event producing islet-cell damage. Nearly half the subjects had had diabetic symptoms for more than 4 weeks before diagnosis.
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PMID:Aetiology of juvenile-onset diabetes. A prospective study. 6 9


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