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)

The insulin and glucagon responses to arginine infusion were investigated in patients with maturity-onset diabetes under control conditions and during metformin therapy. Metformin did not significantly affect the insulin nor the glucagon response to arginine. These data support the concept that biguanide do not act directly on the islets of Langerhans.
 ...
PMID:Influence of metformin on arginine-induced glucagon secretion in human diabetes. 123 63

Thirty-seven children and adolescents of several diagnostic entitites (constitutional growth retardation, diabetes mellitus and pituitary insufficiency) were tested with an i.v. bolus injection of glucagon for plasma human growth hormone (HGH) response. Most of the subjects were also tested for the same purpose by the arginine stimulation test, and the data were compared. It was found that i.v. glucagon is a potent stimulus of human growth hormone release. The HGH is released in two peaks, the first one occuring within 30 min, most probably by a direct effect. The second peak occurs after 120 min, most probably as a secondary effect caused by the drop in blood glucose after its initial rise, which is induced by glucagon. The peak concentrations of HGH induced by glucagon, were very similar to those provoked by i.v. arginine in the same subjects.
 ...
PMID:Comparative HGH response to i.v. glucagon and i.v. arginine stimulation tests in children and adolescents. 124 86

The effect of insulin on the glucagon response to intravenous arginine was studied in eight juvenile-type and six adult-onset diabetics. In the juvenile-type diabetics, concomitant administration of insulin significantly blunted the glucagon response from a mean maximal rise of 310 +/- 54 pg./ml. to only 184 +/- 39 pg./ml. (p less than 0.01), about the same as in nondiabetics. In the adult-onset patients, however, insulin had no effect, the mean maximal rise being 250 +/- 50 pg./ml. without insulin and 307 +/- 71 pg./ml. with insulin (N.S.). This study demonstrates that in juvenile-type diabetics concomitant administration of supraphysiologic quantities of insulin can reduce the exaggerated glucagon response to intravenous arginine to normal, whereas in the adult-type group, it has no apparent effect.
Diabetes 1976 Mar
PMID:Effect of insulin on the exaggerated glucagon response to arginine stimulation in diabetes mellitus. 125 12

Groups of 27 nondiabetic Pima Indians, 34 nondiabetic Caucasians, and 12 diabetic Pima Indians with recent onset of their disease received an arginine infusion to determine if (1) nondiabetic Pima Indians and Caucasians had a similar glucagon response to arginine and (2) diabetic Pimas had excessive glucagon response to arginine as reported in other racial groups. The fasting glucagon levels in the three groups were not significantly different. During arginine monochloride infusion (5 mg./kg./minute for 40 minutes) the diabetic Pimas had glucagon levels significantly higher at 10 minutes and at all sampling points thereafter than the normo-glycemic Pimas. Plasma insulin levels also increased during the infusion but, notably, never differed significantly between these two groups. There was no significant difference in the glucagon levels at any sampling point between the nondiabetic Pimas and Caucasians. The differences in glucagon levels between the nondiabetic and diabetic Indians are similar to those differences reported between diabetic and nondiabetic subjects of other racial origins.
Diabetes 1976 May
PMID:Arginine-stimulated hyperglucagonemia in diabetic Pima Indians. 126 39

We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.
 ...
PMID:Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes. 130 65

Hyperglycemia has been shown to diminish Na(+)-K+ ATPase activity in rabbit aorta. To examine the basis for this effect, aortic rings were incubated for 3 h in Krebs-Henseleit solution containing 5.5 or 44 mM glucose, and Na(+)-K+ ATPase activity was then quantified on the basis of ouabain-sensitive (OS) 86Rb-uptake. Incubation with 44 mM glucose medium caused a 60% decrease in Na(+)-K+ ATPase activity in rings with intact endothelium (from 0.22 +/- 0.01 to 0.091 +/- 0.006 nmol/min per mg dry wt; P less than 0.01). Similar decreases (45%; P less than 0.01) in Na(+)-K+ ATPase activity were seen when rings incubated with 5.5 mM glucose were exposed to NG-monomethyl L-arginine (300 microM), an inhibitor of endothelium-derived nitric oxide (EDNO) synthesis or when the endothelium was removed (43% decrease). The decrease in Na(+)-K+ ATPase activity induced by hyperglycemia was totally reversed upon adding to the medium either L-arginine, a precursor of EDNO biosynthesis or sodium nitroprusside, which bypasses endothelium and directly activates the soluble guanylate cyclase in vascular smooth muscle. A decrease in Na(+)-K+ ATPase activity (42%; P less than 0.05), only seen in the presence of endothelium, was also observed in aortas taken directly from alloxan-induced diabetic rabbits. These studies suggest that the decrease in vascular Na(+)-K+ ATPase activity induced by hyperglycemia is related, at least in part, to a decrease in the basal release of EDNO. They also suggest that alterations in basal EDNO release and possibly Na(+)-K+ ATPase activity contribute to the impairment in vascular relaxation caused by hyperglycemia and diabetes.
 ...
PMID:Endothelium-dependent inhibition of Na(+)-K+ ATPase activity in rabbit aorta by hyperglycemia. Possible role of endothelium-derived nitric oxide. 132 96

Nitric oxide has recently been implicated as the effector molecule that mediates IL-1 beta-induced inhibition of glucose-stimulated insulin secretion and beta-cell specific destruction. The pancreatic islet represents a heterogeneous cell population containing both endocrine cells (beta-[insulin], alpha-]glucagon], gamma[somatostatin], and PP-[polypeptide] secreting cells) and non-endocrine cells (fibroblast, macrophage, endothelial, and dendritic cells). The purpose of this investigation was to determine if the beta-cell, which is selectively destroyed during insulin-dependent diabetes mellitus, is both a source of IL-1 beta-induced nitric oxide production and also a site of action of this free radical. Pretreatment of beta-cells, purified by FACS with IL-1 beta results in a 40% inhibition of glucose-stimulated insulin secretion that is prevented by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (NMMA). IL-1 beta induces the formation of nitric oxide by purified beta-cells as evidenced by the accumulation of cGMP, which is blocked by NMMA. IL-1 beta also induces the accumulation of cGMP by the insulinoma cell line Rin-m5F, and both NMMA as well as the protein synthesis inhibitor cycloheximide prevent this cGMP accumulation. Iron-sulfur proteins appear to be intracellular targets of nitric oxide. IL-1 beta induces the formation of an iron-dinitrosyl complex by Rin-m5F cells indicating that nitric oxide mediates the destruction of iron-sulfur clusters of iron containing enzymes. This is further demonstrated by IL-1 beta-induced inhibition of glucose oxidation by purified beta-cells, mitochondrial aconitase activity of dispersed islet cells, and mitochondrial aconitase activity of Rin-m5F cells, all of which are prevented by NMMA. IL-1 beta does not appear to affect FACS-purified alpha-cell metabolic activity or intracellular cGMP levels, suggesting that IL-1 beta does not exert any effect on alpha-cells. These results demonstrate that the islet beta-cell is a source of IL-1 beta-induced nitric oxide production, and that beta-cell mitochondrial iron-sulfur containing enzymes are one site of action of nitric oxide.
 ...
PMID:Interleukin 1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide. 133 75

This paper reviews recent developments in the biochemistry, pharmacology and physiology of the L-arginine/nitric oxide pathway. Nitric oxide accounts for the biological activity of endothelium-derived relaxing factor (EDRF) and its continuous release plays a crucial role in the regulation of vascular tone and platelet activity. In the nervous system nitric oxide is a neurotransmitter. In the peripheral nervous system, nitroxergic nerves form a part of the non-adrenergic, non-cholinergic innervation of the visceral organs. In the immune system, nitric oxide generated by activated macrophages has tumoricidal and antimicrobial activities. Growing evidence suggests that the alterations in the formation of NO in various tissues contribute to the pathogenesis of various diseases, including hypertension, atherosclerosis, diabetes, subarachnoid hemorrhage and septic shock. Therefore, the improvements in our understanding of the regulation of L-arginine/nitric oxide pathway on the molecular level may lead to the development of new drugs.
 ...
PMID:[Biological role of metabolic pathways from L-arginine to nitric oxide]. 134 93

We investigated in vitro the relaxant effect of exogenous acetylcholine (ACh) and electric-field stimulation (EFS) on rabbit and human corpus cavernosum smooth muscle strips (CC) precontracted with phenylephrine. The effects of EFS and ACh were monitored alone, after muscarinic receptor blockade and after inhibition of nitric oxide (NO) formation with L-N-nitro-arginine (L-NOARG). In rabbit and human CC, both atropine and L-NOARG abolished the relaxant effects of ACh. The relaxant effects of EFS, however, were only slightly reduced by atropine to 97.5 +/- 17.5% in human CC and to 89.0 +/- 6.1% in rabbit CC. L-NOARG further reduced the EFS effects to 0.8 +/- 1.7% in human CC and to 16.2 +/- 8.7% in rabbit CC. In strips obtained from impotent patients with diabetes mellitus, the relaxant effects appeared to be significantly less than in strips from nondiabetic impotent men. Tetrodotoxin blocked the relaxant EFS effects in human and rabbit strips completely. The data indicate the important role of NO in cholinergically induced relaxation of cavernous smooth muscle in rabbits and humans. Our findings support the idea of NO as the nonadrenergic noncholinergic neurotransmitter in penile erection in both species. Rabbit erectile tissue might serve as an in vitro animal model for further investigation.
 ...
PMID:Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth muscle. 135 5

The question of HLA susceptibility to Type 1 (insulin-dependent) diabetes mellitus remains unresolved. In the present study, 127 diabetic patients and 177 unrelated control subjects have been analysed for their class I and class II serological antigens, class II (DR, DQ) DNA restriction fragment length polymorphisms and DQA1 and B1 exon-2 nucleotide sequences and their corresponding amino acid residues. By using the aetiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative Type 1 diabetes susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DR4 less than DR3 less than DR3 or DR4 less than non-Aspartate 57 beta DQ and Arginine 52 alpha DQ less than Arginine 52 alpha DQ. Thus, molecular HLA-DQ markers appear to be more accurate as susceptibility markers than the classic serologically defined ones (DR3 and DR4); however, any effect of DQ markers disappears when non-DR3/DR4 individuals are considered, suggesting that DR factors (or others in between DQ and DR) are also important. In addition, a dominant non-Aspartate 57 beta DQ susceptibility theory does not hold (but a recessive one does) in our diabetic population (probably due to the high frequency of the protective DR7-non-Aspartate 57 beta DQ haplotypes); Arginine 52 alpha DQ is the best single HLA marker found in our population, both as a recessive or as a dominant one. Also there are 13 patients in our sample who bear neither Arginine 52 alpha DQ nor non-Aspartate 57 beta DQ susceptibility factors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison between HLA-DRB and DQ DNA sequences and classic serological markers as type 1 (insulin-dependent) diabetes mellitus predictive risk markers in the Spanish population. 135 47


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