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)

Hepatic lipase has a putative role in the catabolism of HDL particles and, while its activity is dependent upon insulin in the rat, no such insulin responsiveness has been demonstrated in man. We studied 21 patients with type 2 diabetes to examine whether hepatic lipase activity was influenced by hyperinsulinaemia during a 2-4 h isoglycaemic clamp study. Acute changes in lipids, lipoproteins and apolipoproteins were also documented in pre- and post-clamp serum. Hepatic lipase activity during hyperinsulinaemia was compared with activity measured after an equivalent period without insulin. For comparison, nine non-diabetic subjects (matched for age and body mass index) underwent similar clamp studies. In the control experiment without insulin, hepatic lipase activity did not change significantly (mean 9.7 (range 2.3-22.3) in the morning and 9.9 (3.0-22.5) mmol h-1 l-1 in the afternoon, NS). In contrast, after the hyperinsulinaemic clamp, hepatic lipase activity fell significantly in diabetic subjects from 12.8 (4.4-30.6) to 10.4 (3.3-31.3) mmol h-1 l-1, P less than 0.0002 along with serum triglycerides and total and LDL cholesterol. The change in hepatic lipase activity was positively related to the fasting apoprotein B concentration (Spearman r = 0.54, P = 0.016). In the normal subjects, a similar decline in hepatic lipase activity was observed during hyperinsulinaemia (from 15.1 (9.8-32.7) to 12.6 (6.3-28.3) mmol h-1 l-1, P less than 0.01) along with decreases in total, HDL and LDL cholesterol, triglycerides and apoproteins A1 and B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The response of hepatic lipase and serum lipoproteins to acute hyperinsulinaemia in type 2 diabetes. 159 86

Short-term studies have suggested that analogs of prostaglandin E may have favorable effects on the carbohydrate and lipid metabolism in patients with type II diabetes mellitus. The present study was undertaken to investigate the long-term effects of a prostaglandin E1 analog on the regulation of glycemic control and plasma lipids. Twenty patients with type II diabetes received enisoprost, 300 mcg/day, for three months. Fasting serum glucose, glycosylated hemoglobin, insulin and C-peptide levels as well as triglyceride, total cholesterol, high density lipoprotein cholesterol and its subfractions, apolipoproteins B and AI and post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. During the first month, enisoprost treatment caused significant decreases in plasma glucose (baseline = 8.72 +/- 0.39 mmol/L, 4 week = 7.78 +/- 0.5 mmol/L, change = -0.94 +/- 0.28 mmol/L, p less than 0.01) and total cholesterol (baseline = 5.30 +/- 0.23 mmol/L, 4 week = 5.01 +/- 0.26 mmol/L, change = -0.28 +/- 0.06 mmol/L, p less than 0.05). The decrease in cholesterol level was due to a reduction in high density lipoprotein, specifically in high density lipoprotein2 fraction (baseline = 1.29 +/- 0.1 mmol/L, 4 week = 1.12 +/- 0.08 mmol/L, change = -0.018 +/- 0.04 mmol/L, p less than 0.05 for the former and baseline = 0.40 +/- 0.06 mmol/L, 4 week = 0.27 +/- 0.03 mmol/L, change = -0.12 +/- 0.03 mmol/L, p less than 0.05 for the latter): All of these values returned to the pretreatment levels despite continuation of enisoprost.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the prostaglandin E1 analog enisoprost on glucose and lipid metabolism in patients with type II diabetes mellitus. 160 93

In order to assess whether insulin concentration or plasma lipolytic activity has any role in the regulation of HDL cholesterol concentrations in type 2 diabetes, fasting plasma C-peptide and HDL2-cholesterol concentrations and the post-heparin plasma activities of lipoprotein lipase and hepatic endothelial lipase were measured in 148 patients with type 2 diabetes (76 male, 72 female). HDL2-cholesterol was related negatively to hepatic lipase activity in men (r = -0.49, p less than 0.001) and women (r = -0.43, p less than 0.001) and positively to lipoprotein lipase activity in men (r = -0.33, p less than 0.01) and women (r = 0.36, p less than 0.01). A significant inverse relationship was confirmed between C-peptide and the HDL2-cholesterol subfraction in both sexes (men, r = -0.40, p less than 0.001, women r = -0.51, p less than 0.001). This persisted after adjustment for the effects of alcohol intake, mode of hypoglycaemic treatment, plasma glucose and body mass index. The relationship was lost in men and greatly diminished in women when hepatic lipase activity was included in multiple linear regression analysis, whereas the inclusion of lipoprotein lipase activity in the analysis had little effect on the relationship between C-peptide and HDL2-cholesterol. We suggest that hepatic lipase may be partly responsible for the commonly observed inverse relationship between measures of insulin secretion and HDL-cholesterol concentrations. We speculate that this may occur through a direct stimulatory effect of insulin on the enzyme's activity.
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PMID:Association of high density lipoprotein cholesterol with plasma lipolytic activity and C-peptide concentration in type 2 diabetes. 181 5

Abnormalities of plasma lipid and lipoprotein concentrations are common in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In general, individuals with IDDM who are untreated or inadequately treated have elevations in both postprandial and fasting triglyceride levels in association with reduced activity of lipoprotein lipase. Low-density lipoprotein (LDL) cholesterol levels can rise when insulin deficiency impacts on LDL-receptor function. When patients with IDDM are treated and plasma glucose levels well controlled, plasma very-low-density lipoprotein (VLDL) triglyceride and LDL cholesterol levels are usually normal. In addition, plasma high-density lipoprotein (HDL) cholesterol levels are normal or elevated in well-controlled IDDM subjects. In NIDDM, increased VLDL triglyceride and reduced HDL cholesterol concentrations are common and are only partially related to glycemic control. Overproduction of VLDL leads to hypertriglyceridemia, which can be exacerbated if lipoprotein lipase activity is also reduced. The regulation of LDL levels is complex; catabolism can be reduced if significant insulin deficiency exists or increased if significant hypertriglyceridemia is present. The reduced levels of HDL cholesterol in NIDDM appear to be related to increased exchange of HDL cholesteryl esters for VLDL triglycerides, although other mechanisms may exist. The roles of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of NIDDM are complex and require further investigation. Finally, the effects of diabetes on glycosylation of apoproteins; on other lipid enzymes, particularly hepatic triglyceride lipase; on lipoprotein surface lipids; and on hepatic uptake of remnants have only just begun to be defined. In view of the marked increase in atherosclerotic cardiovascular disease in individuals with diabetes mellitus, prompt attention to and aggressive therapy for dyslipidemia should be a central component of care for these patients.
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PMID:Lipoprotein physiology in nondiabetic and diabetic states. Relationship to atherogenesis. 195 76

Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.
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PMID:Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. 220 Jul 27

We investigated the effects of omega-3 fish oil (FO) supplementation on lipid metabolism, glycemic control, and blood pressure (BP) in patients with type II diabetes mellitus. In 22 diabetic patients without overt hyperlipidemia, serum triglyceride, total cholesterol, high density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, HDL3-cholesterol, and apolipoprotein A-I (apo A-I) levels did not change during omega-3 FO supplementation for 8 weeks. The mean serum apo B concentration increased significantly [baseline, 2.56 +/- 0.11 (+/- SEM) mmol/L; 4 weeks, 2.82 +/- 0.13 mmol/L; 8 weeks, 2.80 +/- 0.13 mmol/L; P less than 0.01]. The mean plasma postheparin lipoprotein lipase activity increased transiently during the fourth week (baseline, 168 +/- 17 U/mL; 4 weeks, 182 +/- 18 U/mL; P less than 0.05), whereas postheparin hepatic triglyceride lipase activity did not change. Glycemic control worsened transiently during the fourth week, (baseline, 7.7 +/- 0.4%; 4 weeks, 8.4 +/- 0.3%; P less than 0.05). Both systolic and diastolic BP decreased significantly throughout the study (systolic BP: baseline, 142 +/- 5 mm Hg; 8 weeks, 128 +/- 5 mm Hg; diastolic BP: baseline, 88 +/- 4 mm Hg; 8 weeks, 80 +/- 3 mm Hg; P less than 0.01). These findings suggest that in type II diabetics without overt hyperlipidemia, omega-3 FO supplementation does not improve either the glycemic control or serum lipids, and it is associated with a potentially detrimental rise in serum apo B concentrations. Until more information is available, use of such supplementation should be discouraged.
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PMID:Effects of omega-3 fish oils on lipid metabolism, glycemic control, and blood pressure in type II diabetic patients. 337 25

We investigated the regulation of serum high density lipoprotein (HDL) cholesterol metabolism in patients with type II diabetes mellitus by determining the activities of the two lipolytic enzymes that play major roles in the production and degradation of HDL. The activity of lipoprotein lipase (LPL), the enzyme responsible for HDL cholesterol production, and the activity of hepatic triglyceride lipase (HTGL), the enzyme that facilitates the catabolism of HDL, were measured in plasma obtained after iv injection of heparin. Thirty patients were selected to represent a wide range of serum HDL cholesterol concentrations (low, normal, and high HDL cholesterol groups). Mean lipoprotein lipase activity was similar in all three groups [122 +/- 10 (SEM) U/mL in the low HDL, 141 +/- 11 U/mL in the normal HDL, and 148 +/- 30 U/mL in the high HDL group]. Mean HTGL activity was markedly decreased in the high HDL group; the mean values were 346 +/- 28 U/mL in the low HDL, 320 +/- 25 U/mL in the normal HDL, and 191 +/- 23 U/mL in the high HDL groups, respectively. Body weight and insulin requirement correlated directly with HTGL activity and inversely with serum HDL cholesterol levels. These findings suggest that in type II diabetes mellitus low serum HDL cholesterol levels may be due to an increased rate of clearance by HTGL.
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PMID:Significance of hepatic triglyceride lipase activity in the regulation of serum high density lipoproteins in type II diabetes mellitus. 358 94

Twenty patients (18 men, 2 women) with non-insulin dependent diabetes mellitus (NIDDM) were randomized to receive either gemfibrozil 1200 mg daily or placebo for 3 months in a double-blind study. The effect of gemfibrozil on plasma HDL subfraction distribution was studied with sequential and density gradient ultracentrifugation and in gradient gel electrophoresis. The concentrations of apo A-I, apo A-II, Lp A-I and Lp A-I:A-II particles were measured. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and plasma cholesteryl ester transfer protein (CETP) activities were also determined. Gemfibrozil increased the concentration of HDL cholesterol (P < 0.01), which was due to the rise of HDL3 cholesterol (+16%), while in the placebo group these values remained unchanged. Gemfibrozil increased the concentrations of apo A-I(+12.6%, NS), apo A-II (+28.2%, P < 0.01) and Lp A-I:A-II particles (+21.6%, P < 0.06) but there were no changes in the placebo group. Neither gemfibrozil nor placebo had any effect on the concentration of Lp A-I particles. As determined by density-gradient ultracentrifugation, gemfibrozil increased the concentration of cholesterol in the most dense HDL fractions (mean density 1.193 g/ml, +22%, P < 0.05 and mean density 1.158 g/ml, +19.3%, P < 0.05). In gradient gel electrophoresis, the gemfibrozil-induced elevations of the cholesterol and protein were most pronounced in the HDL3a (8.8-8.2 nm) region. Gemfibrozil increased LPL and HL activities by 14.7% (P < 0.05) and by 18.8% (P < 0.01), respectively, while in the placebo group LPL and HL activities remained unchanged. Plasma CETP activity was also increased during gemfibrozil treatment while in the placebo group it remained unchanged. We conclude that gemfibrozil causes multiple changes in plasma HDL metabolism. The gemfibrozil-induced elevation of HDL3 and dense HDL subpopulations may reflect the concerted action of LPL, HL and CETP on plasma HDL metabolism.
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PMID:Effect of gemfibrozil on high density lipoprotein subspecies in non-insulin dependent diabetes mellitus. Relations to lipolytic enzymes and to the cholesteryl ester transfer protein activity. 825 55

Six patients with type 2 diabetes underwent detailed metabolic studies before and after a minimum of 3 months' glibenclamide therapy. Treatment was associated with a small but significant increase in body weight. Despite improvements in almost all the measured parameters of glucose homeostasis (plasma glucose, glycosylated haemoglobin (HbA1), hepatic glucose production and insulin-mediated glucose disposal) neither fasting serum triglycerides nor HDL cholesterol changed and apoprotein A1 concentrations actually decreased significantly. NEFA and glycerol in fasting plasma and during the clamp studies did not change significantly with treatment. Post-heparin lipoprotein lipase and hepatic lipase activity did not change significantly. Thus, despite substantial improvements in glycaemic control and insulin sensitivity with sulphonylurea therapy, several aspects of lipid and lipoprotein metabolism remain largely unaffected. This small study suggests either that lipoprotein concentrations in type 2 diabetes are not influenced by insulin sensitivity or that the improvement is offset by another change that occurs during this form of therapy. It also suggests that other forms of therapy will be required to improve these cardiovascular risk factors in type 2 diabetes.
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PMID:The effects of glibenclamide on glucose homeostasis and lipoprotein metabolism in poorly controlled type 2 diabetes. 845 16

Elevated levels of plasma triglycerides (TG) and reduced concentrations of HDL cholesterol are very common in patients with diabetes, particularly NIDDM. Although regulation of the plasma concentrations of VLDL, the major TG-rich lipoprotein is extremely complex, it is clear from in vivo kinetic studies that increased rates of secretion of VLDL into plasma is almost uniformly present in patients with NIDDM and hypertriglyceridemia. Recent studies at the cellular level indicate that increased fatty acid flux to the liver, also common in NIDDM (and other insulin-resistant states associated with elevated plasma TG levels), will stimulate the assembly and secretion of apoprotein (apo) B-containing lipoproteins by targeting apoB for secretion rather than intracellular degradation. Increased rates of secretion of VLDL into plasma appears to drive the exchange of TG from these lipoproteins for HDL cholesteryl ester. This exchange, which occurs in plasma, is facilitated by cholesteryl ester transfer protein, and generates a TG-enriched HDL that is a substrate for either hepatic lipase or lipoprotein lipase. When the TG in HDL is hydrolyzed, the resultant particle is smaller, and this appears to affect the binding of the major HDL protein, apoA-I. ApoA-I dissociates from the smaller, lipid-poor HDL, and the free apoA-I (molecular weight 28,000) can be filtered by the glomerulus in the kidney and most likely is degraded in renal tubular cells after reabsorption. Thus, increased free fatty acid transport in plasma, a common abnormality in insulin-resistant states, may be the underlying driving force for the two common lipid abnormalities seen in diabetes.
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PMID:Diabetic dyslipidemia: basic mechanisms underlying the common hypertriglyceridemia and low HDL cholesterol levels. 867 85


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