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

The effects of chronic experimental diabetes on electrophysiological properties, contractile behavior, 45Ca2+ transport, fatty acid profiles and ultrastructural characteristics were studied in enzymatically dissociated ventricular myocytes. Diabetes was induced in rats by streptozotocin administration and animals were killed 8-10 weeks later. Myocytes from diabetic rats exhibited electrical behavior similar to that of myocytes from control rats, but their contractile properties were altered. Their sensitivity of the twitch contractions to various positive and negative inotropic agents (isoproterenol, norepinephrine, phenylephrine, acetylcholine, ouabain and veratridine) was greatly diminished. However, a part of the contractile response (the tonic, sustained contractions) were increased in the diabetic myocytes, indicating that the changes are not caused by a decreased sensitivity of myofilaments. Furthermore, the diabetic myocytes exhibited also significant decrease in total Ca2+ content. The fatty acid profile in the diabetic group was changed mainly in that there were slightly elevated levels of docosahexaenoic acid and diminished levels of palmitic acid. The ultrastructure of the diabetic myocytes was affected only slightly. These investigations offer for the first time a comprehensive picture of changes related to diabetic cardiomyopathy as they occur at the level of cardiomyocytes.
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PMID:Effects of chronic diabetes mellitus on the electrical and contractile activities, 45Ca2+ transport, fatty acid profiles and ultrastructure of isolated rat ventricular myocytes. 338 90

The fatty acid composition of phospholipids and triglycerides in heart muscle was examined in normal and alloxan-diabetic male Wistar rats. In diabetes the major phospholipids, phosphatidyl choline and phosphatidyl ethanolamine, showed significant changes in fatty acid composition, whereas cardiolipin and phosphatidyl serine + phosphatidyl inositol did not show marked changes in fatty acid profile. In phosphatidyl choline there was a significant diminution in arachidonic acid, 20 : 4(n-6) and palmitic acid, 16 : 0, and a corresponding increase in linoleic acid, 18 : 2(n-6), and stearic acid, 18 : 0. In phosphatidyl ethanolamine the level of 20 : 4(n-6) was significantly reduced. The diabetic heart had normal levels of individual phospholipids, whereas the triglycerides were increased by 90% and contained significantly higher levels of 18 : 2(n-6). The results confirm that diabetes is associated with a diminution in fatty acid desaturation, affecting the fatty acid composition of phosphatidyl choline in particular. These changes may be relevant to development of atherosclerosis and relative resistance to catecholamine-induced cardiac necrosis in diabetes.
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PMID:Reduced arachidonic acid levels in major phospholipids of heart muscle in the diabetic rat. 343 62

Fatty acid incorporation into specific phospholipids of isolated islets of the rat was investigated using unsaturated [14C]arachidonic acid. Glucose (25 mM) stimulated the incorporation of arachidonic acid into phosphatidylinositol (PI) and phosphatidylcholine (PC) in a time-related manner correlated with two phases of insulin release. Arachidonate incorporation was inhibited by calcium deprivation. The sulfonylurea tolbutamide stimulated an early monophasic release of insulin that was accompanied by increased [14C]arachidonate incorporation into PI and PC. The cholinergic agonist and insulin secretagogue, carbamylcholine, also promoted the incorporation of [14C]arachidonate into PI/phosphatidylserine (PS) and PC fractions. 2-Deoxy-D-glucose, which does not support insulin release, did not enhance arachidonate incorporation into phospholipids. However, phenylephrine, an inhibitor of glucose-induced insulin secretion, stimulated arachidonate turnover in PI. p-Bromophenacyl bromide, an inhibitor of phospholipase A2, markedly depressed both glucose-stimulated arachidonate incorporation into phospholipids and insulin release. The stimulated release of arachidonate from endogenous radiolabeled phospholipids provided additional evidence that phospholipase A2 mediates glucose stimulation. However, since glucose also promoted the incorporation of saturated [14C]palmitic acid into PE (phosphatidylethanolamine) and PI/PS fractions, a phospholipase A1 may also mediate the glucose response. Thus, fatty acid incorporation into islet phospholipids mediates the effects of various secretagogues on insulin release. However, the ability of phenylephrine to stimulate arachidonyl PI turnover suggests that fatty acid turnover is not a sufficient stimulus for release. Augmented levels of unsaturated fatty acids in islet cell membranes may promote fusion or activate enzymes important for hormone release.
Diabetes 1983 Jan
PMID:Fatty acid incorporation into phospholipids of isolated pancreatic islets of the rat. Relationship to insulin release. 633 3

Streptozotocin diabetes [45 mg/kg] in rats fed on a standard diet, with insulin substitutional therapy - 66 [nkat/kg]/d [[4 U/kg b.w.]d] for the first 3 days - led during an 8 days' experiment to marked hypertriglyceridaemia [4.86 mmol/l] and to triglyceride accumulation in the liver [22.35 mmol/kg]. The endogenous triglyceride secretion rate, studied by means of a Triton WR 1339 block of lipoprotein lipase, was almost 30 % lower in diabetic rats. The half-time of plasma 14C-triglycerides [labelled endogenously with 14C-1-palmitic acid] almost doubled and the fractional turnover rate fell to half the value in the control animals. Hypertriglyceridaemia in diabetic rats [60 % insulin deficiency] is caused by slower removal of lipoprotein triglycerides from the plasma space, owing to reduced lipolytic activity in the peripheral tissues.
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PMID:Kinetics of plasma triglycerides in rats with streptozotocin diabetes. 645 36

Moderate insulin deficiency was reported to be accompanied by an increased production of intestinal very low density lipoprotein (VLDL) triglyceride in the rat. Because plasma free fatty acids (FFA) are incorporated into triglyceride by intestinal mucosa of rats and humans and plasma FFA are increased in insulin-deficient diabetes mellitus, we investigated several aspects of the intestinal metabolism of plasma FFA in diabetic rats. All experiments were performed on the third day following the i.v. injection of streptozotocin (45 mg/kg body weight) or buffer alone. A (14 C)palmitic acid-rat serum complex was rapidly injected intravenously and its initial uptake by small bowel mucosa, the intracellular incorporation into lipids and water soluble metabolites and the specific radioactivity of triglycerides of mucosal homogenates was determined. No significant differences could be found between diabetic and control rats at 2 and 5 min after 14C-palmitate i.v., suggesting that neither the influx of plasma free fatty acids into intestinal mucosal cells nor their initial intracellular metabolic pathways are significantly altered in moderately diabetic rats. A pronounced decrease in intestinal mucosal triglyceride at 10 min after 14C-palmitate i.v. might be interpreted as indirect evidence for an enhanced triglyceride efflux from intestinal mucosa into mesenteric lymph in diabetic rats.
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PMID:Intestinal metabolism of plasma free fatty acids in streptozotocin diabetic rats. 652 11

The authors studied acute changes in the fatty acid composition of the tissues of streptozotocin-diabetic rats. They found that streptozotocin diabetes led to changes in the total lipids fatty acid spectrum in serum and in tissues (liver, adipose tissue, renal cortex diaphragm). After only 7 days' diabetes there was an increase in the percentual proportion of saturated fatty acids and a decrease in the amount of polyene fatty acids in the serum and in all the above tissue of diabetic animals. Palmitic acid (16:0) participated in the increase in the proportion of saturated fatty acids in all the given tissues, while stearic acid (18:0) played a role in the increase in the renal cortex and the serum. Among the monoene acids, there was a drop in the proportion of palmitoleic acid (16:1) in the adipose tissue and serum and in the amount of oleic acid (18:1) in the renal cortex, liver and muscle. Linoleic acid (18:2) played a role in the decrease in the proportion of polyene acids in all the given tissues and the serum, while arachidonic acid (20:4) was involved in the drop in the renal cortex, liver and muscle. The results show that diabetes leads to changes in the fatty acid composition of the renal cortex and muscle, as well as of the liver and adipose tissue. At present it is not yet clear whether there is an absolute decrease in the proportion of essential fatty acids, or whether diabetes is characterized by an increase in the amount of lipids in both serum and tissues.
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PMID:The fatty acid composition of the tissues of streptozotocin-diabetic rats. 664 91

Forty-eight patients with symptoms of angina pectoris were studied for adipose tissue fatty acid composition and cardiovascular risk factors while hospitalized for selective coronary angiography. Patients with manifest diabetes mellitus and deviations form the "normal" customary diet were excluded. Pairwise comparison between the groups with absent, slight, moderate, and severe coronary arteriosclerosis showed reasonable comparability for age, relative body weight, and skinfold measurements. The proportion of smokers, but not of hypertensives, showed a significant positive relationship with the degree of arteriosclerosis. Serum cholesterol was similar in all four groups, while triglycerides were clearly, but not significantly (P greater than 0.05) higher in patients with coronary arteriosclerosis. The oral glucose tolerance test (OGTT) index was significantly higher in moderate and severe disease. Significantly higher proportions for palmitic acid lower proportions for linoleic acid were also found in these two groups. Multiple linear regression analysis showed a positive association with coronary arteriosclerosis for: OGTT index greater than palmitic acid greater than arachidonic acid greater than triglycerides. The close negative association between the proportion of stearic acid in adipose tissue and coronary heart disease observed in two previous studies could not be confirmed. On the basis of the present study, stearic acid correlates with age rather than with arteriosclerotic disease.
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PMID:Fatty acid composition of adipose tissue, blood, lipids, and glucose tolerance in patients with different degrees of angiographically documented coronary arteriosclerosis. 680 19

Intravenous administration of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid had no effect on the proportion of pyruvate dehydrogenase complex in the active form in heart, diaphragm or gastrocnemius muscles or in liver, kidney or adipose tissue of fed normal rats. The compound reversed the effect of 48h starvation (which decreased the proportion of active complex) in heart muscle, partially reversed the effect of starvation in kidney, but had no effect in the other tissues listed. The compound failed to reverse the effect of alloxan-diabetes (which decreased the proportion of active complex) in any of these tissues. In perfused hearts of fed normal rats, 2-tetradecylglycidate reversed effects of palmitate (which decreased the proportion of active complex), but it had no effect in the absence of palmitate. In perfused hearts of 48h-starved rats the compound increased the proportion of active complex to that found in fed normal rats in the presence or absence of insulin. In perfused hearts of diabetic rats the compound normalized the proportion of active complex in the presence of insulin, but not in its absence. Palmitate reversed the effects of 2-tetradecylglycidate in perfused hearts of starved or diabetic rats. Evidence is given that 2-tetradecylglycidate only reverses effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle under conditions in which it inhibits fatty acid oxidation. It is concluded that effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle are dependent on fatty acid oxidation. Insulin had no effect on the proportion of active complex in hearts or diaphragms of fed or starved rats in vitro. In perfused hearts of alloxan-diabetic rats, insulin induced a modest increase in the proportion of active complex in the presence of albumin, but not in its absence.
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PMID:Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats. 715 98

The ultrastructural effects of a single brief intra-arterial infusion of palmitic, linoleic and acetoacetic acid on the arterial endothelium of the rat were investigated, and the following results obtained: (1) Palmitic acid, infused at a concentration of 4 mM/l, damaged the arterial lining by producing large cytoplasmic clefts and occasional blebbing and lysis of the endothelial cells. By contrast, linoleic acid, infused at the same concentration, had no damaging effects on arterial endothelium. (2) Acetoacetic acid damaged the arterial wall when infused at concentrations of 0.2 mM/l or higher by inducing extreme swelling and loss of cristae of the mitochondria in arterial endothelium and myocytes. The above results raise the possibility that (a) high saturated fatty acid diets may promote atherosclerosis not only by inducing hypercholesterolemia but also by injuring the arterial lining, and (b) diabetes may promote atherosclerosis not only by inducing hyperlipemia but also by damaging the arterial wall during periods of uncontrolled ketoacidosis.
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PMID:Arterial effects of palmitic, linoleic and acetoacetic acid. 722 70

The in vivo effects of pantethine were investigated on serum lipids and platelet lipid and platelet functions in 31 diabetic patients with hyperlipidemia. Pantethine decreased cholesterol from 236 +/- 62 mg/dl (M +/- SD) to 217 +/- 51 mg/dl (p less than 0.01) and increased high density lipoprotein cholesterol from 40 +/- 11mg/dl to 43 +/- 15 mg/dl. The diabetic platelets were larger when accompanied by higher microviscosity that healthy platelets. The characteristics of lipid composition in diabetic platelets were high levels of free cholesterol, phospholipid, triglyceride, cholesterol ester, palmitoleic acid, linoleic acid and palmitoleic acid/palmitic acid and low levels of the molar ratio of free cholesterol/phospholipids, phosphatidylethanolamine, oleic acid, arachidonic acid and oleic acid/stearic acid. Pantethine normalized these values of fatty acids to the control levels, and concomitantly reduced significantly the hyperaggregation of platelets induced by 10(6) M ADP and the hyper-ADP release reaction from platelets when exposed to 2 microgram of collagen, and made the volume smaller and the microviscosity lower after oral administration. From these data, it was concluded that pantethine normalized the abnormalities of serum lipids as well as platelet lipid compositions and subsequently reduced the hyper-aggregation and hyper-release reactions through the changes of volume and microviscosity of the platelets in diabetes mellitus with hyperlipidemia.
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PMID:Influence of pantethine on platelet volume, microviscosity, lipid composition and functions in diabetes mellitus with hyperlipidemia. 725 94


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