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 effects of intensive insulin therapy on metabolic control, fatty acid metabolism and platelet function were studied in 18 non-obese non-insulin-dependent diabetics (NIDDs) with secondary failure to oral antidiabetic drugs (OAD). Patients were randomly allocated either to continue maximal OAD (Group I, n = 9) or to receive a multiple injection regimen of insulin therapy (Group II, n = 9) for a 6-month period. At baseline both groups were identical for clinical and biological parameters. At study day 180, fasting blood glucose (P < 0.01) and mean capillary blood glucose (P < 0.05) were reduced in group II but the difference between HbA1 percentages remained non-significant. At study day 60, in total plasma lipids, oleic acid was lower (P < 0.05), linoleic acid (P < 0.05) and the sum of polunsaturated fatty acids (PUFA) (P < 0.05) were higher in group II than I. In triglycerides, palmitic acid was lower in group II at study days 60 (P < 0.01) and 180 (P < 0.05), whereas gamma-linolenic acid was decreased (P < 0.05) at study day 180 only. A similar change was noted in cholesterol esters for gamma-linolenic acid at study day 60 (P < 0.05). No difference was noted between both groups for platelet agregation, insulin sensitivity and clinical parameters despite a significant increase in body weight in group II at study day 180. Positive correlations were obtained between the content of different lipid fractions in some PUFA and the glucose clearance. We conclude that optimized insulin therapy in NIDDs with secondary failure to OAD leads to a transient improvement in glucidic and lipidic metabolism but has no significant effect upon platelet aggregation and insulin sensitivity.
Diabetes Res Clin Pract 1995 Apr
PMID:Effects of insulin therapy upon plasma lipid fatty acids and platelet aggregation in NIDDM with secondary failure to oral antidiabetic agents. 758 8

The aim of the study was to ascertain the metabolic and dietary determinants of changes in serum lipids during a 15-month diet therapy of obese patients (n = 71, 41 males, 30 females) with recently diagnosed Type 2 (non-insulin-dependent) diabetes. The subjects lost weight and improvement in glycaemic control was observed, but due to variation in individual responses the mean serum total cholesterol or non-HDL cholesterol did not change significantly. The proportion of palmitic acid decreased and that of linoleic acid increased in serum lipids during the study, and serum triglycerides decreased and HDL-cholesterol increased. In univariate analyses, decreased serum triglyceride level was associated with serum triglycerides at baseline, decreases in body mass index, fasting blood glucose and palmitic acid proportion of serum triglycerides, and the intake of saturated fats and dietary fibre, but in multiple regression analyses the determinants for decreased serum triglycerides were high serum triglycerides at baseline and a decreased proportion of palmitic acid in serum triglycerides. In univariate analysis, increased HDL-cholesterol was associated with the baseline HDL-cholesterol, decrease in the triceps/subscapularis ratio and the intake of saturated and mono-unsaturated fatty acids, but none of these variables had an independent contribution to the increase in serum HDL-cholesterol in multiple regression analysis. In conclusion, a reduction of palmitic acid in the serum lipids, which was probably due to reduction of dietary saturated fatty acids, had beneficial effects on serum lipids in obese patients with Type 2 diabetes, independently of weight loss and improvement in glycaemic control.
 ...
PMID:Metabolic and dietary determinants of serum lipids in obese patients with recently diagnosed non-insulin-dependent diabetes. 802 29

Palmitate has been shown to stimulate glucose transport, translocation of GLUT4 and insulin receptor autophosphorylation in isolated rat adipocytes (Biochem Biophys Res Commun 177:343-49, 1991). Here we further characterize the ability of short-term treatment with free fatty acids to stimulate glucose transport in isolated rat adipocytes and demonstrate that prolonged treatment induces insulin resistance. Treatment of adipocytes for 15 min with 1 mM myristate (14:0), palmitate (16:0), or stearate (18:0) stimulates glucose transport by 119 +/- 33, 89 +/- 29, and 114 +/- 30%, respectively. In contrast, oleate (cis 18:1), 1), elaidate (trans 18:1), and linoleate (cis 18:2) do not stimulate glucose transport. Palmitate stimulates glucose transport in a concentration-dependent manner, demonstrating saturation at 1 mM and half-maximal stimulation at 0.25-0.5 mM. Prolonged treatment (4 h) of rat adipocytes with 1 mM palmitate induces insulin resistance. After a 4-h preincubation with palmitate (1 mM), insulin stimulates glucose transport in rat adipocytes by 4.4-fold +/- 0.8, vs. 8.8-fold +/- 0.8 in controls (n = 3). Palmitate-induced resistant cells demonstrated a 40% inhibition in maximal insulin responsiveness with little change in insulin sensitivity. Insulin binding is only slightly decreased (8%) in palmitate-pretreated cells. These studies indicate that saturated fatty acids stimulate glucose transport acutely and on prolonged exposure induce insulin resistance via a post-insulin binding defect. The underlying molecular mechanisms of insulin resistance induced by prolonged treatment with saturated fatty acids may now be investigated using this unique cellular model.
Diabetes 1994 Apr
PMID:Saturated fatty acid-induced insulin resistance in rat adipocytes. 813 59

The membrane fluidity of intact erythrocytes from diabetic patients and sex-matched controls has been examined between 20 and 40 degrees C by electron spin resonance spectroscopy using the 5-doxyl palmitic acid spin label. In contrast to the normal erythrocytes, in both types of diabetes a significant non-linearity was found around 30 degrees C in the fluidity-temperature plots of the lipid bilayer. This was assigned to a phase transition normally absent in the 20-40 degrees C range. The magnitude of the bilayer fluidity showed a little decrease in insulin-dependent diabetes and an increasing trend vanishing around 37 degrees C in non-insulin-dependent diabetes. In addition, we observed two protein-immobilized lipid subpopulations, showing slightly higher apparent concentrations and modified fluidity in diabetes. Membrane composition alterations, mainly in the fatty acid concentrations, may explain the fluidity changes. Our results, although preliminary in a clinical sense because the number of investigated patients was too small, evidenced specific and complex changes of the erythrocyte membrane fluidity in diabetes and demonstrated the high potential of the spin label approach for the diabetic medicine.
 ...
PMID:Electron spin resonance study of the erythrocyte membrane fluidity changes in diabetes. 814 79

The mechanisms by which fatty acids increase insulin release are not known. In this study, mouse islets were used as a model and palmitate as a reference compound to study in vitro how saturated fatty acids influence pancreatic beta-cells. Palmitate (625 microM) was bound to albumin. It did not affect basal insulin release (3 mM glucose) but increased the release induced by 10-15 mM glucose. This effect was dependent on the concentration of free rather than total palmitate. It was reversible and abolished by epinephrine, diazoxide, nimodipine, or omission of extracellular Ca. Bromopalmitate and methyl palmoxirate, two inhibitors of fatty acid oxidation, were ineffective alone, and only bromopalmitate partially inhibited the effects of palmitate on insulin release. The increase in insulin release produced by palmitate could not be ascribed to a blockade of ATP-sensitive K(+)-channels because the fatty acid only barely decreased 86Rb efflux and did not depolarize beta-cells in 3 mM glucose. The small effect on 86Rb efflux might be attributed to a slight rise in the ATP/ADP ratio. No such rise occurred when palmitate was tested in 15 mM glucose, and the fatty acid consistently accelerated 86Rb efflux under these conditions. Measurements of beta-cell membrane potential (intracellular microelectrodes) and of free cytoplasmic calcium (Cai2+) in beta-cells (Fura 2 technique) showed that palmitate increases Ca2+ influx; it also caused a very small mobilization of intracellular Ca. The persistence of this stimulation of Ca2+ influx in the presence of diazoxide and high K+ suggests that palmitate might act on Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 May
PMID:Mechanisms of the stimulation of insulin release by saturated fatty acids. A study of palmitate effects in mouse beta-cells. 816 48

To examine whether hyperglycemia is an independent regulator of adipose tissue lipolysis, we measured palmitate flux ([3H]palmitate) on two occasions in eight volunteers with insulin-dependent diabetes. On one. occasion, euglycemia was maintained for 4 h continuously; on a different occasion, hyperglycemia (plasma glucose, 12 mmol/l) was induced after 2 h of euglycemia. Palmitate flux decreased from 1.39 +/- 0.22 to 1.25 +/- 0.18 mumol.kg-1 x min-1 during sustained euglycemia and from 1.43 +/- 0.24 to 1.13 +/- 0.19 mumol.kg-1 x min-1 during the transition from the euglycemic to the hyperglycemic study intervals. There were no significant differences between the changes in palmitate flux from the first to the second study interval on the control (euglycemia-euglycemia) and experimental (euglycemia-hyperglycemia) study days and no difference between palmitate flux on different study days. Thus, in the face of euinsulinemia, euglucagonemia, and the absence of somatostatin, no effect of hyperglycemia on free fatty acid metabolism could be detected in humans.
 ...
PMID:Lack of effect of hyperglycemia on lipolysis in humans. 827 35

To test the hypothesis that the high circulating FFA levels in the diabetes of obesity could contribute to the altered dynamics of insulin secretion seen in that condition, insulin release was measured in isolated perifused rat islet cells, without or with added palmitate. Acutely, as in other systems, palmitate (1 mM) stimulated insulin release. Palmitate (1 mM) suppressed both first and second phase insulin release after 2, 3, or 4 h of perifusion, but not after 1 h. No significant effect was noted with 0.3 mM palmitate, and the effect was maximal at 1 mM. The stimulatory effects of arginine were essentially unaffected. Tolbutamide (1 mM) reversed or counteracted the effect. Glucose oxidation was suppressed in islets incubated with 1 mM palmitate for 4 h. Inhibitors of fat oxidation, alpha-bromostearate (1 mM) and methyl-3-tetradecylglycidate (100 microM) reversed the effects of palmitate on glucose-stimulated insulin release and glucose oxidation. Thus, prolonged incubation of rat islet cells with 1 mM palmitate could suppress the glucose-stimulated release of insulin from perifused rat islets. This suppression could be reversed by inhibitors of fat oxidation. This supports the hypothesis that elevated FFA levels and/or increased fat oxidation could contribute to the altered dynamics of insulin secretion in obese diabetics by fuel antagonism as well as the previously documented suppression of peripheral glucose uptake and stimulation of hepatic gluconeogenesis and may be a key link between obesity and the development of diabetes.
 ...
PMID:Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release. 831 69

Compliance with dietary recommendations and the effect of intensified dietary therapy on energy and nutrient intakes and fatty acid composition of serum lipids were studied in 86 obese subjects (aged 40 to 64 years) with recently diagnosed non-insulin-dependent diabetes mellitus (NIDDM). After three months of basic education, the subjects were randomly separated into an intervention group (n = 40) and a conventional treatment group (n = 46). Members of the intervention group participated in 12 months of intensified education; those in the conventional group visited local health centers. Compliance with dietary instructions was monitored through food records. Intensified dietary therapy resulted in greater weight loss, better metabolic control, and a less atherogenic lipid profile than conventional treatment. Intake of energy and saturated fatty acids tended to decline in the intervention group. A higher percentage of patients in the intervention group had a total fat intake of 30% of energy or less after 15 months (32.5% [12 of 38] vs 17.4% [8 of 46]). Similarly, more patients in the intervention group had a saturated fatty acid intake of 10% or less of total energy intake at the end of the study (35.0% [13 of 38] vs 8.7% [4 of 46]). The mean dietary cholesterol intake was within recommendations in both groups at the end of the study. The relative percentage of linoleic acid of serum lipids increased significantly and the relative percentage of palmitic acid of serum triglycerides, phospholipids, and cholesterol esters decreased in the intervention group. These changes indicate that intensified dietary therapy improved the quality of fat in the diet of patients with NIDDM.
 ...
PMID:Impact of intensified dietary therapy on energy and nutrient intakes and fatty acid composition of serum lipids in patients with recently diagnosed non-insulin-dependent diabetes mellitus. 838 12

Insulin demand varies with meal intake and physical activity. In this study the feasibility of using two implants to meet varying insulin demands was tested in rabbits with alloxan-induced diabetes. One group of severely diabetic rabbits was maintained on a basal dose released by a 50-mg implant made of a compressed admixture of 15% insulin in palmitic acid. The other group of mildly diabetic rabbits required no basal dose implant, but displayed a transient hyperglycaemia as well upon challenge. The supplemental dose was provided by another silicone implant with reservoirs containing 6 mg of compressed insulin. Serous fluid entered the 100 microliters internal volume of the silicone implant slowly through an orifice, and dissolved some of the solid insulin. When required, sideways compression of this second implant over the abdominal skin fold of the rabbit delivered the supplemental dose. Typically, a severely diabetic rabbit on a basal dose implant exhibited a transient hyperglycaemia after drinking sweetened water, which raised the blood glucose from 5.4 +/- 1.3 mmol l-1 to 14.0 +/- 0.5 mmol l-1 for 3 to 4.5 h. In the three test runs, the supplemental bolus of insulin from the silicone implant interrupted the expected rise in blood glucose at 6.1 +/- 2.2 mmol l-1 within 1 to 2 h, which then decreased to 3.0 +/- 0.2 mmol l-1 for 4 to 5 h before returning to the basal level. A mildly diabetic rabbit showed a blood glucose level of 10.5 +/- 1.9 mmol l-1 without the basal dose implant.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Control of hyperglycaemia in diabetic rabbits by a combination of implants. 845 87

Inflammatory cytokines may participate in the destruction of pancreatic islets during the pathogenesis of insulin-dependent diabetes mellitus, and the cytokine interleukin-1 (IL-1) strongly inhibits insulin secretion from rat pancreatic islets by a process which involves induction of expression of the inducible isoform of nitric oxide synthase and the overproduction of nitric oxide. The signaling events between IL-1 receptor occupancy and induction of nitric oxide synthase in rat islets involve activation of the transcriptional activator NFkappa B. Because sphingomyelin hydrolysis has been implicated as a signaling process both in NFkappa B activation and in IL-1 action in some cells, we have examined the potential involvement of sphingomyelin hydrolysis in the induction of islet nitric oxide overproduction by IL-1. Rat islet sphingomyelin pools were radiolabeled with [3H]choline, and sphingomyelin was then isolated by normal phase HPLC. Electrospray ionization-mass spectrometric analysis revealed islet sphingomyelin consists of at least 4 distinct molecular species, and the most abundant of them contained sphingosine as the long chain base and a residue of palmitic acid as the fatty acid substituent. Molecular species containing residues of stearic acid and arachidic acid were also observed. Neither interleukin-1 nor tumor necrosis factor-alpha was found to induce hydrolysis of islet sphingomyelin species, and neither an exogenous, cell-permeant ceramide species (N-acetyl-D-sphingosine) nor exogenous sphingomyelinase mimicked or potentiated the effect of IL-1 to increase rat islet nitric oxide generation, as reflected by nitrite production. Similar findings were obtained with RINm5F insulinoma cells and with mouse pancreatic islets. These findings provide the first information on the molecular species of sphingomyelin in pancreatic islets and suggest that sphingomyelin hydrolysis is not involved in the signaling pathway whereby IL-1 induces the overproduction of nitric oxide by pancreatic islets.
 ...
PMID:Characterization of the sphingomyelin content of isolated pancreatic islets. Evaluation of the role of sphingomyelin hydrolysis in the action of interleukin-1 to induce islet overproduction of nitric oxide. 860 64


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