Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 37-amino acid peptide called amylin is a major component of the islet amyloid deposited in the pancreases of persons with type 2 diabetes mellitus. We report the isolation of a partial cDNA clone and a phage lambda genomic clone of the coding region of the amylin gene. The DNA sequence encodes a protein sequence identical to that of amylin isolated from the amyloid found in the diabetic pancreas and shows that amylin is likely to be synthesized as a precursor peptide, now named proamylin. We have demonstrated that the amylin gene is present on chromosome 12 and that it is probably transcribed in the islets of Langerhans. The sequences of the genes for amylin and the calcitonin gene-related peptides (CGRPs) show strong similarity, especially over their 5' coding regions, where both peptides have a conserved intramolecular disulfide bridge, and also over their 3' coding regions, where the presence of a glycine codon strongly suggests that the carboxyl-terminal residue of amylin, like that of CGRP, is amidated. To examine the functional relevance of these posttranslational modifications, the biological activity of amylin synthesized with or without the disulfide bridge and/or amidation was measured. It was found that both features are necessary for full biological activity, thereby confirming the functional importance of those regions of the molecule whose sequences are conserved at both protein and genetic levels.
Proc Natl Acad Sci U S A 1989 Dec
PMID:Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus. 269 69

Amylin, the major peptide component of the islet amyloid commonly found in the pancreases of patients with type 2 (non-insulin-dependent) diabetes mellitus (NIDDM), is a recently discovered islet polypeptide. This peptide has many structural and functional features suggesting that it is a novel hormone, which may control carbohydrate metabolism in partnership with insulin and other glucoregulatory factors. Amylin is synthesised in, and probably secreted from, the beta-cells of the islets of Langerhans, where it has recently been immunolocalised to secretory granules. DNA cloning studies indicate that in the human and the rat, amylin is generated from a precursor, preproamylin, which displays a typical signal peptide followed by a small prohormone-like sequence containing the amylin sequence. The presence of the signal peptide suggests that amylin is secreted and plays a physiological role. Amylin is probably generated by proteolytic processing similar to that for proinsulin and other islet prohormones. The human amylin gene encodes the complete polypeptide precursor in two exons which are separated by an intron of approx. 5 kb, and is located on chromosome 12. Amylin is a potent modulator of glycogen synthesis and glucose uptake in skeletal muscle, and is capable of inducing an insulin-resistant state in this tissue in vitro, and perhaps also in the liver in vivo. In normal metabolism, amylin could act in concert with insulin as a signal for the body to switch the site of carbohydrate disposal from glycogen to longer-term stores in adipose tissue, by making skeletal muscle relatively insulin-resistant, whilst at the same time leaving rates of insulin-stimulated carbohydrate metabolism in adipose tissue unaltered. Several lines of evidence now implicate elevated amylin levels in the pathogenic mechanisms underlying NIDDM, and suggest to us that the obesity which frequently accompanies this syndrome is a result of, rather than a risk factor for, NIDDM. Following the beta-cell destruction which occurs in type 1 (insulin-dependent) diabetes mellitus (IDDM), it is probable that amylin secretion disappears in addition to that of insulin. As patients with insulin-treated IDDM frequently experience problems with hypoglycaemia, and as amylin acts to modulate the action of insulin in various tissues, it is possible that amylin deficiency may contribute to morbidity in insulin-treated IDDM, perhaps through the loss of a natural damping mechanism which guards against hypoglycaemia under conditions of normal physiology.
Biochim Biophys Acta 1989 Dec 14
PMID:Amylin and the amylin gene: structure, function and relationship to islet amyloid and to diabetes mellitus. 269 Sep 58

Both sporadic cases and outbreaks of legionnaire's disease have been reported. To date, no outbreaks have occurred but several case reports have been published in Switzerland. The newly organized surveillance system of notifiable diseases, introduced in 1987, makes it possible for the first time to analyze reported sporadic cases more precisely. In 1988, the laboratories reported a total of 32 cases with cultural or serologic proof of legionellosis. In 75% of cases patients were aged over 40 years, 78% occurred among males. The majority of them were known to be smokers. In 9 cases an underlying predisposing condition was known: hairy cell leukemia (3 cases), immune hemolytic anemia (1), type 2 diabetes (2), chronic lung disease (1), heart failure (1). The case fatality was 9%. A possible source of exposure, such as air-conditioned rooms or evaporative condensers, was reported in 4 cases.
Schweiz Med Wochenschr 1989 Dec 23
PMID:[Epidemiology of legionnaires' disease in Switzerland in 1988]. 269 49

Aging and disease may contribute to alterations in drug pharmacokinetics. The purpose of this study was to determine the effects of aging, the presence of NIDDM, and multiple dosing on the pharmacokinetics of glipizide, an oral hypoglycemic drug. Ten healthy young men (under age 25), ten healthy older men (over age 65) and 15 older diabetic men ingested a single 5 mg tablet of glipizide after an overnight fast. Blood samples for measurement of serum glipizide were obtained over the next 24 hours. The study was repeated in the diabetics after 2 weeks of daily therapy. The mean values for Tmax (range 2.0-2.5 hours), Cmax (385-465 micrograms/l), and t1/2 (4.0-4.2 hours) were not significantly different in the three populations after single doses of glipizide. Several subjects in each population had slow absorption, with peak concentrations delayed for up to 12 hours. Only one elderly diabetic subject had evidence of drug accumulation at steady state. AUC, Cl, Vss and V area were not significantly different in the three populations or at steady state, but there was a trend for AUC to be smaller and each of the other parameters to be increased in the older diabetics. The young subjects had a significantly higher fp (0.83%) than either of the two elderly groups (0.55-0.64%), but Cl int did not differ between groups. Age, diabetes, and multiple dosing appear to have little effect on the pharmacokinetics of glipizide and should have little influence on the clinical response to this drug.
J Clin Pharmacol 1989 Dec
PMID:Glipizide pharmacokinetics: effects of age, diabetes, and multiple dosing. 269 2

The chronically hyperinsulinemic Zucker fatty rat, with peripheral insulin resistance and glucose intolerance, represents a model of noninsulin dependent diabetes mellitus (NIDDM). These animals have elevated hepatic glycogen levels. Hepatic levels of synthase phosphatase and phosphorylase phosphatase, which are diminished in the IDDM rat, were markedly increased in the obese rats. Glyburide, a sulfonylurea used in treatment of NIDDM, resulted in reduced levels of glycemia and increased insulin levels in Zucker rats. Hepatic glycogen levels were increased, as was the activation of glycogen synthase, although there were no effects of drug administration on synthase phosphatase or phosphorylase phosphatase activities. G6P levels were increased by glyburide in lean rats but not in obese animals. These effects of glyburide on liver glycogen metabolism are accounted for via potentiation of the glycogenic effects of insulin.
Life Sci 1987 Dec 14
PMID:Hepatic glycogen synthase phosphatase and phosphorylase phosphatase activities are increased in obese (fa/fa) hyperinsulinemic Zucker rats: effects of glyburide administration. 282 45

10 patients with type 2 diabetes mellitus, in stable weight and diet therapy, followed a 2 months nutritional supplementation with guar, 15 g/day. Their previous nutritional and pharmacological therapy was not modified throughout the study. No changes occurred in body weight or major parameters of metabolic control. However, a significant fall occurred in fasting plasma, total and LDL cholesterol, and apolipoprotein B concentrations. Insulin sensitivity, measured by the "steady state plasma glucose", obtained after a 150 min glucose-insulin-somatostatin infusion, improved in all patients but two. A significant correlation was observed between steady state plasma glucose variations, the glycosylated haemoglobin A1c (r = 0.70; p less than 0.005), total (r = 0.77; p less than 0.001), and LDL cholesterol (r = 0.69; p less than 0.005) and apolipoprotein B concentrations (r = 0.75; p less than 0.005).
Minerva Med 1987 Dec 15
PMID:[Effect of guar on plasma lipids and on the biological activity of insulin in patients with type 2 diabetes mellitus]. 282 61

In 249 individuals of different age groups, taking a high fibre diet naturally, glucose tolerance studies were done after a standard glucose load (1.73 g/kg body weight or 100 g glucose). A group of 156 of the subjects were also studied after a standardized hospital meal (258 g carbohydrate, 14 g fat, 47 g protein and 32 g fibre). Mean blood glucose values after the high fibre mixed meal were lower than after the glucose load. The mean 2-h postprandial blood glucose was 2-4 mmol/l lower compared to that observed in other studies using less carbohydrate. The postprandial blood glucose pattern is likely to be as a result of (a) the large amount of carbohydrate and fibre in the test meal (b) the fat and protein content of the test meal (c) the habitual intake of such a meal and (d) the nature and type of fibre consumed in the meal. Among the subjects 1.2 per cent were found to have non-insulin dependent diabetes mellitus while 2 per cent had impaired glucose tolerance. This prevalence of non-insulin dependent diabetes mellitus in subjects, who came predominantly from a rural or semi-rural background, is lower than that found in urban areas of Northern India. The effect of age on glucose tolerance was clearly seen after the glucose load (0.4 mol/l/decade) and after the mixed meal (0.1 mmol/l/decade). These findings suggest the potential of the constituents of a typical North Indian diet in improving glucose tolerance.
Eur J Clin Nutr 1988 Dec
PMID:Glucose tolerance in north Indians taking a high fibre diet. 285 48

The addition of vegetable fibres to the diabetic diet has been reported to ameliorate glycaemic and plasma lipid profiles, and Guar flour seems to obtain the best results. At its usual dose, Guar produces several gastro-intestinal side effects. A lower dose (4 + 4 g/day) was therefore employed in 10 non-insulin dependent diabetics (NIDD). The following parameters were measured at the end of treatment and after a control period: HbA1 levels, hepatic glucose production (3H-Glucose infusion), peripheral sensitivity to insulin and insulin secretion (hyperglycaemic clamp), and specific insulin binding to isolated monocytes. The ultracentrifugal plasma lipid pattern was also measured. No significant body weight change was recorded during the study. A significant glycaemic and insulinaemic decrease in the fasting state was observed after Guar, together with a significant decrease of HbA1 levels (from 8.5 +/- 0.4 to 7.9 +/- 0.4%, p less than 0.05) and amelioration of peripheral sensitivity to insulin (M/I = 14.3 +/- 6.6 versus 24.3 +/- 8.8, p less than 0.025; 50% increase of insulin binding to circulating monocytes) without significant variation of the fasting hepatic glucose production. Decreased B-cell stimulation by flattening post-prandial glycaemic peaks may be an explanation of the reduction of insulin resistance via down-regulation mechanism. As far as the lipid profile is concerned, a significant reduction in total and LDL cholesterol (p less than 0.05 and p less than 0.01) and an increase in HDL-phospholipids (p less than 0.05) were recorded after Guar. These results suggest that Guar in low doses is well accepted and can contribute to a better glycaemic and lipaemic control in NIDDM.
Diabete Metab 1985 Dec
PMID:Moderate guar-gum addition to usual diet improves peripheral sensitivity to insulin and lipaemic profile in NIDDM. 300 79

Erythrocyte sodium, potassium and water contents and sodium fluxes were measured in both normotensive and hypertensive patients with either insulin dependent or non-insulin dependent diabetes mellitus. Hypertensive patients were studied again after two months' treatment with captopril. There were no differences in erythrocyte ion contents or concentrations but sodium fluxes may have been lower in insulin dependent patients and in hypertensive patients. The most marked erythrocyte defects associated with hypertension were low erythrocyte water content and increased potassium concentration in non-insulin dependent diabetic patients. Treatment with captopril caused an increase in erythrocyte water and a decrease in ion content and concentration. In non-insulin dependent diabetic patients, who had the greatest increases in erythrocyte water and falls in potassium concentration, frusemide-sensitive sodium-potassium co-transport activity was reduced. The reduction in blood pressure with captopril treatment was related to the initial erythrocyte sodium content.
J Hum Hypertens 1988 Dec
PMID:Hypertension and diabetes mellitus: erythrocyte electrolytes and the effect of captopril treatment. 307 39

The aim of this study was to evaluate the correlations of the C-peptide and insulin responses after stimulation with glucagon intravenously as well as the 24-h urinary excretion of C-peptide to the C-peptide response to a standard mixed meal in 30 patients with non-insulin dependent diabetes mellitus (NIDDM). Fasting plasma C-peptide as well as the C-peptide and insulin responses to glucagon, showed similar but only modest correlations with the C-peptide response to the meal. Urinary C-peptide showed no correlation with the C-peptide response to the meal, but correlated modestly with fasting plasma C-peptide (r = 0.55, p less than 0.01). The C-peptide and insulin responses after meal stimulation correlated modestly inversely with HbA1. In conclusion, measurement of C-peptide in fasting state, as well as measurements of C-peptide and insulin after glucagon stimulation, only modestly predict the C-peptide response to physiologic stimulation in NIDDM. Twenty-four-hour urinary C-peptide excretion does not predict this response. Patients with NIDDM seem to show a better metabolic control if they have a more pronounced beta-cell response to physiologic stimulation.
Scand J Clin Lab Invest 1988 Dec
PMID:The beta-cell response to glucagon and mixed meal stimulation in non-insulin dependent diabetes. 307 Jul 18


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