Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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)
 ...
PMID:The response of hepatic lipase and serum lipoproteins to acute hyperinsulinaemia in type 2 diabetes. 159 86

Lipase activities were measured at pH 4 and pH 8 in the placentas of rats made diabetic by streptozotocin treatment and also in the placentas of women classified as having 1) impaired glucose tolerance or type 2 diabetes, 2) type 1 diabetes with no associated vascular complication, and 3) type 1 diabetes with associated vascular disease. In both sets of experiments, the placentas were compared with normal control groups. The placental lipase activity measured at pH 8 was not significantly different in either streptozotocin-treated rats or impaired glucose tolerance/diabetic women as compared with controls, whereas the lipase activity measured at pH 4 increased significantly as compared with controls in both species. Furthermore, in the women there was a significant correlation between placental lipase activity at pH 4 and birth weight in impaired glucose tolerance/type 2 diabetes. It is suggested that the increased placental lipase activity may contribute to the increased fetal weight in human diabetic pregnancy, by contributing to the increased fat transfer across the placenta from mother to fetus.
 ...
PMID:The effects of diabetes on placental lipase activity in the rat and human. 180 50

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.
 ...
PMID:Association of high density lipoprotein cholesterol with plasma lipolytic activity and C-peptide concentration in type 2 diabetes. 181 5

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.
 ...
PMID:Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. 220 Jul 27

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.
 ...
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.
 ...
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.
 ...
PMID:Diabetic dyslipidemia: basic mechanisms underlying the common hypertriglyceridemia and low HDL cholesterol levels. 867 85

This study evaluates the effects of insulin versus glibenclamide on lipoprotein metabolism at comparable levels of blood glucose control, in particular on the concentration and distribution of VLDL subfractions and lipolytic enzyme activities in nine NIDDM men (aged 56 +/- 3 years, BMI 26.5 +/- 0.9 kg/m2) (means +/- SE) participating in a crossover study. After a 3-week washout period, patients were randomly assigned to 2-month treatment periods (insulin or glibenclamide); thereafter, each patient crossed to the other treatment. At the end of each period, mean daily blood glucose (MDBG), HbA1e, plasma lipids, lipoproteins (VLDL, LDL, HDL), lipoprotein subfractions (VLDL1, 2, 3; HDL2, HDL3), and post-heparin lipase activities (lipoprotein lipase [LPL], hepatic lipase [HL]) were evaluated. Although glucose control was similar at the end of both periods (MDBG 8.3 +/- 0.3 vs. 7.9 +/- 0.3 mmol/l; HbA1c 7.4 +/- 0.3 vs. 7.0 +/- 0.2%, insulin versus glibenclamide), insulin compared with glibenclamide induced a significant reduction in plasma triglycerides (0.9 +/- 0.1 vs. 1.1 +/- 0.1 mmol/l, P < 0.05), VLDL triglycerides (50.1 +/- 12.2 vs. 63.6 +/- 12.3 mg/dl, P < 0.02), VLDL1 lipid concentration (24.9 +/- 7.5 vs. 39.9 +/- 9.5 mg/dl, P < 0.006), and increased HDL2 cholesterol (25.2 +/- 1.6 vs. 20.3 +/- 1.3 mg/dl, P < 0.03). In terms of VLDL percentage subfraction distribution, with insulin, there was a decrease in the larger subfractions (VLDL1 26.5 +/- 3.0 vs. 37.8 +/- 3.4%, P < 0.02) and an increase in the smallest (VLDL3 47.3 +/- 3.8 vs. 37.3 +/- 3.3%, P < 0.05). Moreover, HL activity was significantly lower after insulin than after glibenclamide (HL 247.2 +/- 22.3 vs. 263.5 +/- 22.6 mU/ml, P < 0.05). In conclusion, compared with glibenclamide, insulin treatment (independent of variations in glucose control) is able to decrease significantly plasma triglycerides, to increase HDL2 cholesterol, and to reduce only the concentration of the larger VLDL subfractions, with a consequent redistribution of their profile.
 ...
PMID:Insulin and sulfonylurea therapy in NIDDM patients. Are the effects on lipoprotein metabolism different even with similar blood glucose control? 931 56

Segregation analysis of body-mass index (BMI) supported recessive inheritance of obesity, in pedigrees ascertained through siblings with non-insulin dependent diabetes mellitus (NIDDM). BMI was estimated as 39 kg/m2 for those subjects homozygous at the inferred locus. Two-locus segregation analysis provided weak support for a second recessive locus, with BMI estimated as 32 kg/m2 for homozygotes. NIDDM prevalence was increased among those subjects presumed to be homozygous at either locus. Using both parametric and nonparametric methods, we found no evidence of linkage of obesity to any of nine candidate genes/regions, including the Prader-Willi chromosomal region (PWS), the human homologue of the mouse agouti gene (ASP), and the genes for leptin (OB), the leptin receptor (OBR/DB), the beta3-adrenergic receptor (ADRB3), lipoprotein lipase (LPL), hepatic lipase (LIPC), glycogen synthase (GYS), and tumor necrosis factor alpha (TNFA).
 ...
PMID:Recessive inheritance of obesity in familial non-insulin-dependent diabetes mellitus, and lack of linkage to nine candidate genes. 932 33

Obesity is common in NIDDM; in a cohort of 314 diabetics in Singapore, 44.3% are overweight. Management of obesity in diabetics differs from that in non-diabetics in that it is more urgent; weight maintenance is more difficult and hypoglycaemic medication may cause weight changes. Like in the non-diabetic, management of obesity in diabetic requires a pragmatic and realistic approach. A team approach is required: the help of the nurse educator, the dietitian, behaviour modification therapist, exercise therapist etc are required. A detailed history, careful physical examination and relevant investigations are required to assess the severity of the diabetic state and to exclude an occasional underlying cause of the obesity in the obese NIDDM. Weight loss is urgent in the obese NIDDM, especially those with android obesity. There must be a reduction in caloric intake. Weight loss leads to improvement in the glucose tolerance, insulin sensitivity, reduction in lipid levels and fall in blood pressure in the hypertensive. Exercise is of limited value except in the younger obese NIDDM. Metformin is the hypoglycaemic drug of choice as it leads to consistent weight reduction. The sulphonylureas may cause weight gain. Insulin should be avoided where possible as it causes further weight gain. Other hypoglycaemic agents include Glucobay (alpha-glucosidase inhibitor) and Troglitazone (insulin sensitizer) which do not alter the weight. Orlistat (lipase inhibitor) is promising as it causes reduction of weight, blood-glucose and lipid levels. Anti-obesity drugs (noradrenergic and serotonergic agents) have modest effects on weight reduction in the obese NIDDM; a widely use preparation, Dexfenfluramine (Adifax) has been withdrawn because of side effects. Surgery such as gastric plication is the last resort in treating the morbidly obese NIDDM. The discovery of leptin in 1994 has led to intense research into energy homeostasis in obesity; hopefully this will lead to better treatment of obesity in diabetics and non-diabetics.
 ...
PMID:Management of obesity in NIDDM (non-insulin-dependent diabetes mellitus). 984 3


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