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

There is a very high probability that lipoprotein metabolism plays a central role in the etiology of coronary heart disease. In sedentary persons one way to favorably alter lipoprotein metabolism and possibly delay the progression of coronary atherosclerosis is by an increase in their habitual physical activity. More physically active persons tend to have lower plasma triglycerides and very low density lipoprotein concentrations, and a greater high-density lipoprotein mass due to higher concentrations of the subfraction HDL2 and apoprotein A-I. Plasma low-density lipoprotein concentrations usually are not significantly reduced by exercise unless accompanied by weight loss, but there may be important changes in the distribution among the low-density subfractions. These exercise effects are most likely mediated by alterations in the activity of enzymes involved in the synthesis, transport and catabolism of the various lipoproteins including lipoprotein lipase, hepatic lipase and lecithin: cholesterol acyltransferase. In healthy persons as well as in patients with ischemic heart disease, diabetes and renal failure, an increase in moderate-intensity, endurance-type activity requiring an expenditure of approximately 4 MJ (1,000 kcal) per week usually produce favorable lipoprotein changes. Above this level a dose-response relationship exists, with greater changes occurring up to energy expenditures of 19 MJ (4,500 kcal) per week.
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PMID:The influence of exercise training on plasma lipids and lipoproteins in health and disease. 353 12

The objective of this paper is to review the extent and mechanisms of lipoprotein alterations in pregnancy, present new data relating to placental lipid transport in normal humans and diabetic animals and consider possible effects on fetal growth and development in normal and diabetic pregnancy. The concentration of all lipoprotein fractions increases during pregnancy. VLDL cholesterol and triglyceride increase 2.5-fold over prepregnancy levels and LDL cholesterol increases 1.6-fold, all with peak levels at term. HDL cholesterol is maximally increased in midgestation by 1.45-fold and subsequently declines to 1.15-fold at term. The mechanisms of these lipoprotein changes have not been studied in humans but the hypertriglyceridemia in animal models is related to enhanced VLDL entry into the circulation. In addition, diminished adipose tissue lipoprotein lipase (LPL) activity in late gestation may cause a rerouting of triglyceride fatty acids to other tissues such as muscle and uterus for oxidation, rather than storage, since triglyceride transport is not reduced in pregnancy. All of these changes appear to be sex hormone mediated. In diabetic pregnancies, the available data indicate that triglyceride concentrations are increased and HDL cholesterol concentrations are decreased with reference to lipoproteins in nondiabetic pregnant women. Previously unpublished data show that a transplacental FFA gradient exists across the umbilical circulation in the direction of the fetus and is proportional to the maternal FFA concentration. No gradient is seen for triglyceride or total plasma cholesterol. However, transport of unmeasured amounts of triglyceride fatty acids may still occur via placental LPL and be exaggerated in diabetes where LPL declines in adipose tissue but not in placenta. The mechanism of transplacental cholesterol transport remains to be defined. Preliminary studies suggest that it depends on HDL as well as LDL since both can provide cholesterol for placental progesterone synthesis. In addition, fetal weight and length are associated with maternal apoproteins A-I and A-II, both major apoproteins of HDL. By lowering HDL in pregnancy, diabetes mellitus could negatively affect these relationships. In conclusion, sex hormone mediated modifications of lipoprotein physiology are described in pregnancy which may enhance triglyceride fatty acid transport to muscle for oxidation and LDL and HDL cholesterol delivery to growing maternal and fetal tissues, a process that diabetes could globally disrupt.
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PMID:Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effects of diabetes. 354 67

High levels of triglycerides (TG) and free fatty acids (FFA) in maternal plasma, in diabetes, promote fat passage to the fetus. In the streptozotocin-diabetic rat a significant correlation exists between maternal plasma and fetal tissue lipid contents, as shown by the accretion of labeled fatty acids or linoleate used as markers of maternal fat transfer. The passage of lipids through the placenta is not direct--this organ serves as an interim storage barrier with its lipid content increasing in proportion to the maternal TG and FFA level. Very low density lipoprotein (VLDL) TG are taken up with the aid of lipoprotein lipase as evident from TG = glycerol exchange when doubly labeled VLDL-TG are presented to the placenta. Esterification rate of albumin-bound FFA is considerably higher indicating that the rate of TG lipolysis is rate limiting and that the FFA are the main precursor of the placental lipids. The uptake of both FFA and VLDL-TG is associated with the retention of a substantial amount of FFA in the placenta. The size of the FFA pool corresponds to the size of the extracellular fluid space. The FFA cannot be eluted by repeated washing, suggesting that they are membrane bound. Placental slices with prelabeled TG gradually release FFA into the medium upon reincubation with FFA-free albumin, indicating that TG and FFA traverse the placenta in part by a sequential process of esterification and lipolysis and in part by diffusion as FFA. The latter are probably moving from the maternal to the fetal side within the interfacial capillary membrane lipids.
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PMID:Placental function in maternal-fetal fat transport in diabetes. 355 56

With use of the alpha-glucosidase inhibitor bay g 5421 (acarbose), it is possible to improve glycemic profiles in diabetics without a concomitant increase in insulin levels or weight reduction. We have taken advantage of this feature to test whether an improvement in glycemic control alone can ameliorate some of the known abnormalities of type II diabetes (ie, impaired insulin secretion, elevated rate of basal hepatic glucose output, peripheral insulin resistance). We have studied eight type II diabetics (mean +/- SE fasting serum glucose 193 +/- 25 mg/dL) before and after 2 weeks of acarbose therapy (100 mg with each meal). Assessment of endogenous insulin secretion, peripheral and hepatic insulin sensitivity, and adipose tissue lipoprotein lipase (ATLPL) activity were performed. Results showed significant lowering of postprandial glucose excursions above basal but no change in basal serum glucose levels, marked reduction in fasting and day-long triglyceride levels and in spite of a reduction in ATLPL activity, an increase in hepatic sensitivity to insulin's ability to suppress hepatic glucose output, and no effect on peripheral insulin sensitivity. In conclusion, inhibition of carbohydrate digestion with alpha-glucosidase inhibitors ameliorates many of the metabolic abnormalities in type II (noninsulin-dependent diabetics), suggesting that agents of this type can be of therapeutic value.
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PMID:The effect of short-term alpha-glucosidase inhibition on carbohydrate and lipid metabolism in type II (noninsulin-dependent) diabetics. 355 48

Human adipose tissue lipoprotein lipase (LPL) is stimulated in vivo by an insulin-glucose infusion. However, previous work by us showed no effect of physiologic insulin concentrations on LPL in isolated human adipocytes. To pursue further the regulation of LPL in vitro, primary cultures of isolated human adipocytes were prepared and exposed to glucose concentrations of 0-4.5 mg/ml. LPL activity was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests (EXT). After 5 h in culture, a stimulatory effect of glucose on HR was observed. After 24 h there was a gradual increase in CM, HR, and EXT in parallel with increasing glucose concentrations of 0-1.0 mg/ml. At glucose concentrations greater than 1.0 mg/ml, however, there was a decrease in CM. At a glucose concentration of 4.5 mg/ml, CM was only 51 +/- 14% (P less than .02) of its value at glucose concentrations of 1.0 mg/ml. Cellular LPL (HR and EXT) was not affected by high glucose concentrations. Response of cellular LPL to the hormonal regulator insulin-like growth factor I (IGF-I) was modulated by medium glucose. HR in cultures treated with 50 ng/ml IGF-I was 166 +/- 40 and 147 +/- 23% of HR in control cultures at glucose concentrations of 1.0 and 2.5 mg/ml, respectively (P less than or equal to .05). However, IGF-I failed to stimulate HR at glucose concentrations greater than 2.5 mg/ml or less than 1.0 mg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Nov
PMID:Regulation of lipoprotein lipase by glucose in primary cultures of isolated human adipocytes. Relevance to hypertriglyceridemia of diabetes. 366 16

The effect of progressive, diabetes-associated adiposity on reproductive tract structure and function was examined in 4- to 16-week-old C57BL/KsJ, control (+/?) and diabetic (db/db) mice. Uterine and ovarian tissues were analyzed by transmission electron microscopy for ultrastructural changes associated with increased intracellular lipid accumulation. In addition, the same tissues were analyzed for changes in activity of tissue lipoprotein lipase, an enzyme that hydrolyzes lipoprotein-associated triacylglycerols and supports the cellular uptake and storage of free fatty acids. Between 8 and 16 weeks of age, intracellular lipid deposits increased dramatically in the ovarian granulosa, thecal and stromal cell populations, as well as in the uterine epithelium, of diabetic mice compared to controls. By 16 weeks of age, the lipid deposits essentially occupied the entire cytoplasmic area of both the ovarian and uterine cell types in diabetics. The basal lamina underlying the uterine epithelium was expanded in the diabetics relative to controls, and the hyperglycemic condition induced an observable increase in endometrial intercellular space that was occupied by a hyaline type of ground substance of unknown composition and origin. In association with these structural changes, both ovarian and uterine lipase activities were greatly increased in the db/db mice compared with controls. These data suggest that the structural adiposity and functional decline in reproductive tract condition of the db/db mutants are related to the enhanced cellular lipid deposition observed in this species. These changes in structural and metabolic parameters are related to the reproductive incompetence characteristic of this murine model.
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PMID:Ultrastructural and metabolic changes associated with reproductive tract atrophy and adiposity in diabetic female mice. 378 18

A neutral triacylglycerol lipase activity that is separate and distinct from lipoprotein lipase (LPL) could be measured in homogenates of myocardial cells if protamine sulphate and high concentrations of albumin were included in the assay. This neutral lipase was predominantly particulate, with the highest relative specific activity in microsomal subcellular fractions. The induction of diabetes by the administration of streptozotocin to rats resulted in a decrease in LPL activity in myocyte homogenates and in particulate subcellular fractions, but the percentage of cellular LPL activity that was released during incubation of myocytes with heparin was normal. In contrast, neutral lipase activity was increased in diabetic myocyte homogenates and microsomal fractions. Acid triacylglycerol lipase activity was not changed in diabetic myocytes. The decrease in LPL in myocytes owing to diabetes may result in the decreased functional LPL activity at the capillary endothelium of the diabetic heart.
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PMID:Effect of diabetes on acid and neutral triacylglycerol lipase and on lipoprotein lipase activities in isolated myocardial cells from rat heart. 380 Sep 35

Although lipoprotein lipase (LPL) is believed to be rate limiting in the catabolism of triglyceride-rich lipoproteins, LPL activity has not correlated with plasma triglyceride concentrations in experimental rat diabetes. To gather more information about this enzyme system in diabetes, LPL activities were measured in representative tissues from control and streptozocin-induced diabetic rats fed fat-free chow and in 48-h-starved animals. The DNA content of each tissue was determined so that LPL activity could be expressed in a way that was unaffected by tissue wasting. Diabetic animals lost approximately 20% of their body mass. Adipose tissue and soleus muscle cell masses were reduced, and there was marked fat atrophy at necropsy. Adipose tissue LPL was decreased in both starved and diabetic animals, whereas skeletal muscle activities were variably affected. Lipase content and distribution among the individual organs were calculated with published data for rat carcass composition. In diabetic rats, total LPL (adipose tissue, muscle, and parenchymal organs) was reduced by nearly two-thirds so that skeletal muscle became the predominant source of LPL. Ketonuria was less frequent in diabetic than in starved rats (P less than .018) despite their severe wasting. Serum triglyceride concentrations were higher in ketonuric than nonketonuric diabetic animals, and severe hypertriglyceridemia was seen exclusively in heavily ketonuric animals. These observations together with published information suggest that plasma triglyceride concentrations in the rat model are determined by a complex interplay between very-low-density lipoprotein synthesis, the capacity of the LPL removal system, properties of the lipoprotein substrate, and other unidentified factors.
Diabetes 1987 Apr
PMID:Relationship of organ lipoprotein lipase activity and ketonuria to hypertriglyceridemia in starved and streptozocin-induced diabetic rats. 381 3

Circulating triglyceride is cleared by a combination of hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL). Although LPL has been extensively studied in diabetes, the effect of insulinization on H-TGL activity has not been well characterized. To determine whether H-TGL activity is altered in insulin-deficient diabetes, postheparin plasma was obtained from eight beagle dogs: three normal (nondiabetic) control dogs and five pancreatectomized diabetic dogs were studied acutely in poor diabetic control (underinsulinized), and again in short-term good control (well insulinized). Plasma glucose, measured at the start of the studies, was 88 +/- 10 mg/100 mL (mean +/- SD) in the normal control dogs, 434 +/- 31 mL in pancreatectomized dogs in poor diabetic control, and 87 +/- 16 in good diabetic control. Peak (five minutes) postheparin plasma H-TGL activity was increased in dogs in poor diabetic control (212 +/- 43 nmol FFA/min/mL) v the normal control dogs (135 +/- 21 nmol FFA/min/mL, P less than 0.02). When the dogs were in good diabetic control, the peak H-TGL (202 +/- 40 nmol FFA/min/mL) was also significantly increased compared with the level in normal dogs, while the sum of five and 45 minute postheparin H-TGL levels for the dogs in good diabetic control was less than when they were in poor diabetic control (P less than 0.01). Thus, insulin-deficient diabetes in dogs increases H-TGL, and short-term improvement of glycemic control with insulin partially corrects this increase.
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PMID:Hepatic triglyceride lipase in diabetic dogs. 388 96

Severely diabetic (150 mg/kg streptozocin, STZ) rats were transplanted with fetal pancreatic islets: (1) under the renal capsule to model peripheral insulin delivery, and (2) into the splenic pulp to model portal delivery. In both groups of transplanted animals, weight gain and blood glucose levels were normal as were peripheral plasma insulin levels. Plasma nonesterified fatty acids, glycerol, acetoacetate, 3-hydroxybutyrate, triglyceride, and cholesterol levels were normal in the two groups of transplanted animals as were VLDL-triglyceride turnover and total ketone body turnover. Adipose tissue lipoprotein lipase activity was also normal in both the fed and fasting states. The findings indicate that consistent normoglycemia and normalization of many aspects of lipid metabolism can be achieved in the rat with peripheral insulin delivery without associated hyperinsulinemia.
Diabetes 1985 Jun
PMID:Comparison of portal and peripheral insulin delivery on lipid metabolism in streptozocin-diabetic rats. 389 72


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