Postprandial adipose tissue lipoprotein lipase activity in primary hypertriglyceridemia

The fasting activity of adipose tissue lipoprotein lipase has been previously reported to be either normal or reduced in subjects with a primary form of hypertriglyceridemia. The postprandial activity of adipose tissue lipoprotein lipase has not been previously reported in these subjects. In subjects with primary hypertriglyceridemia the fasting lipoprotein lipase activity eluted from pieces of adipose tissue by heparin and the enzyme activity present in extracts of acetone-ether tissue powders were similar to the level of enzyme activity found in normal subjects. There also was no difference in the postprandial adipose tissue heparin-elutable lipoprotein lipase activity between these two groups when measured after high carbohydrate feeding. When the subjects with primary hypertriglyceridemia were further subdivided by genetic diagnosis, there was no difference in the level of adipose tissue lipoprotein lipase of subjects with familial hypertriglyceridemia, familial combined hyperlipidemia, or in those in whom no specific genetic diagnosis could be made. The change in lipoprotein lipase activity after feeding was inversely related to the fasting enzyme level in both the normal subjects (r = ?0.58, p < 0.05, n = 12) and the hypertriglyceridemic subjects (r = ?0.92, p < 0.01, n = 11). In the normal subjects, the plasma triglyceride response to feeding correlated inversely with the postprandial change in lipoprotein lipase activity (r = ?0.76, p < 0.02, n = 12). Adipose tissue lipoprotein lipase activity in patients with primary lipoprotein lipase deficiency was markedly reduced in the fasting state and remained essentially zero after feeding. This suggests that a functional role exists for the enzyme activity as measured.     

Lipid and lipoprotein triglyceride and cholesterol interrelationships: Effects of sex,hormone use,and hyperlipidemia

The interrelationships of lipid and lipoprotein cholesterol and triglyceride concentrations in normolipidemic and hyperlipidemic employees of the Pacific Northwest Bell Telephone Company were examined bivariately using correlation analysis and multivariately by factor analysis. Application of the latter resulted in the identification of three distinct lipoprotein lipid clusters, which succinctly describes their metabolic relationships. Among normolipidemic subjects, the interrelationships were found to be similar in male and female subjects, but hormone use by women considerably altered interrelationships that involved high-density lipoprotein cholesterol (HDL-C) and triglyceride. Among hyperlipidemic subjects, we found that elevation in cholesterol level alone rarely altered relationships, but elevation in triglyceride level either alone or in conjunction with an elevation in cholesterol concentration was associated with substantial changes in relationships involving the low-density lipoprotein (LDL) fraction. In many instances, positive relationships between LDL cholesterol (LDL-C) and other lipoprotein lipids became inverse in the presence of triglyceride elevation. We conclude that hormone use by women and hypertriglyceridemia with or without an elevation in cholesterol level clearly alter lipoprotein relationships, whereas pure hypercholesterolemia does not. These alterations provide a basis for investigating pathophysiologic mechanisms in hypertriglyceridemia.     

Heterogeneity of primary lipoprotein lipase deficiency

Lipoprotein lipase activity appeared in plasma within 10 min of beginning a heparin infusion in control subjects in whom adipose tissue lipoprotein lipase activity was normal. Plasma lipoprotein lipase activity was maintained throughout a heparin infusion lasting 4–6 hr. Three subjects with primary diminished adipose tissue lipoprotein lipase activity had markedly decreased lipoprotein lipase activity for the duration of the heparin infusion. However, the findings in two additional subjects suggest that the activity released during the early phase and during the late phase of the heparin infusion might come from different tissues. One subject had no adipose tissue lipoprotein lipase activity, but had levels of lipoprotein lipase in postheparin plasma similar to controls during the early phase of the heparin infusion. The other subject had normal adipose tissue lipoprotein lipase activity in the fasted and fed state, yet had little lipoprotein lipase activity in postheparin plasma during the early phase of the heparin infusion. This patient developed levels similar to that seen in plasma in the control subjects at the end of the heparin infusion. These findings suggest that (1) the activity that appears soon after initiating the heparin infusion is released from tissues other than adipose tissue, while that appearing later is of adipose tissue origin and (2) subjects with primary abnormalities of lipoprotein lipase form a heterogenous group of individuals.     

Growth-hormone-induced changes in postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities

A comparison of treated and untreated patients with growth hormone deficiency revealed that administration of growth hormone reduced lipoprotein lipase and hepatic lipase activities, total cholesterol, and high-density lipoprotein cholesterol concentrations. The possible significance of these results is discussed.     

The relationship of exercise and diet on high-density lipoprotein cholesterol levels in women

The relationship of exercise and diet on high-density lipoprotein (HDL) cholesterol was investigated in 45 long-distance runners (LD), 49 joggers (J), and 47 inactive (I) women. Fasting plasma triglycerides (TG), HDL cholesterol, total cholesterol (TC), and percent body fat (%BF) were measured in women ages 24-58 yr. TG levels were significantly lower in LD compared to I (p less than 0.02). Although TC was not significantly different among groups, HDL-cholesterol was higher in LD (78 mg/dl) compared to J (70 mg/dl) or I (62 mg/dl) (p less than 0.001). Multiple regression analyses indicated that alterations of plasma lipids and lipoprotein levels could not be attributed to intake differences of nutrients. Distance run and %BF were the strongest predictors of HDL-cholesterol in women. LD (23 %BF) were leaner than J (26 %BF) or I (30 %BF); however, when results were adjusted for %BF, significant differences between exercise groups remained for HDL cholesterol.     

Postheparin plasma triglyceride lipases in chronic hemodialysis: evidence for a role for hepatic lipase in lipoprotein metabolism.

Elevated plasma triglyceride levels frequently occur in patients with chronic renal failure receiving longterm hemodialysis. Postheparin plasma lipolytic activity, an indirect measure of triglyceride removal, is low in hemodialysis patients, but this activity measures both hepatic triglyceride lipase (HTGL) and lipoprotein lipase (LPL). To determine if HTGL and/or LPL are low in hemodialysis patients and related to lipoprotein lipid levels, both activities were measured by a selective antibody-inhibition technique in postheparin plasma from 20 hemodialysis patients with a wide range of plasma triglyceride levels ($\text{104–676}\text{mg}\text{100}\text{ml}$), and the relationships between the enzyme activities and lipoprotein lipid levels were examined. To more accurately compare subjects, the heparin doses were adjusted for the differences in plasma volumes between the hemodialysis patients and the nonuremic control subjects. Hemodialysis patients with elevated plasma triglyceride levels (↑TG) had HTGL levels (148 ± 67 nmole/min/ml, n=10) which were similar to the dialysis patients with normal triglyceride levels (nlTG) (134 ± 64 nmole/min/ml, n=10) and both groups were significantly lower (p<0.05, p<0.02, respectively) than the levels of the control subjects (208 ± 61 nmole/min/ml, n=11). The HTGL levels of the hemodialysis patients with ↑TG correlated inversely with plasma total cholesterol (r_s=−0.833, p<0.01) and the d>1.006 fraction cholesterol (low + high density lipoproteins, r_s=−0.863,p<0.01), but not triglyceride. The activity of HTGL of the entire group of hemodialysis patients correlated with the plasma total cholesterol (r_s=−0.615, p<0.01), d>1.006 fraction cholesterol (r_s=−0.731, p<0.01) and low density lipoprotein cholesterol (r_s=−0.659, p<0.01). The LPL levels of the hemodialysis patients with the ↑TG (52 ± 24 nmole/min/ml) were lower than those with nlTG (70 ± 25 nmole/min/ml) and the levels of both hemodialysis groups were significantly lower (p<0.01, p<0.02, respectively) than the LPL levels in the control subjects (110 ± 43 nmole/min/ml). The ratio of LPL to total postheparin plasma lipolytic activity was lower in the hemodialysis patients with ↑TG (0.32 ± 0.15), than in the hemodialysis patients with nlTG (0.47 ± 0.18, p<0.06) or the control subjects (0.45 ± 0.09, p<0.05). Unlike HTGL, the levels of LPL did not correlate with lipid levels in the hemodialysis patients. Thus, both postheparin plasma HTGL and LPL are low in hemodialysis patients. The relationship between HTGL and low density lipoprotein cholesterol levels suggests a possible role for HTGL in low density lipoprotein catabolism.     

Lipid metabolism in pregnancy. VIII. Effects of dietary fat versus carbohydrate on lipoprotein and hepatic lipids and tissue triglyceride lipases

We have asked, is hypertriglyceridemia in the fed state in pregnancy due to intolerance to exogenous fat, accumulation of endogenous triglycerides, or accumulation of remnants of d < 1.006 lipoprotein metabolism? To answer these questions, we fed rat-free diets high in starch or sucrose, or diets containing fat or fat plus cholesterol to pregnant and nonpregnant rats for 12 days until gestational day 21 (term = 22 days). Blood was obtained 0, 4, or 8 hr after removal of food from the cages. Lipid concentrations were determined in chylomicrons and very low, low, and high density lipoproteins. Hypertriglyceridemia in pregnancy exists on both starch and sucrose containing fat-free diets and is exaggerated 4 and 8 hr after food is removed from the cage. The triglyceride rise occurs in d < 1.006 lipoproteins. With fat feeding, chylomicron triglyceride concentrations are not significantly elevated in pregnant rats, 0 or 8 hr postabsorptively despite greater food intake in pregnancy. In contrast, very low density lipoprotein (VLDL) triglyceride concentrations are elevated at all times following fat feeding in pregnant compared to nonpregnant animals. A significant contribution of lipoprotein remnants to the triglyceride rise in d < 1.006 lipoproteins seems unlikely since an isolated increase in VLDL cholesterol is not observed. No statistically significant accumulation of hepatic triglycerides occurs on any diet in pregnancy. Diet induced shifts in adipose tissue and muscle lipoprotein lipase activity are exaggerated in pregnancy while hepase in unaffected. Fetal weight is similar on all diets except sucrose where weight is reduced. Conclusions: Hypertriglyceridemia in fed pregnant rats is due to an increase in endogenous triglycerides. Remnant lipid accumulation does not appear to contribute to the endogenous hypertriglyceridemia. There is no intolerance to exogenous (dietary) fat. The results are compatible with an unimpaired delivery of exogenous fat to fat oxidizing tissues thereby maximizing glucose availability for fetal growth.     

Plasma lipoprotein abnormalities associated with acquired hepatic triglyceride lipase deficiency

Two enzymes, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL), are released into human plasma after intravenous injection of heparin. LPL is the major enzyme responsible for initiating catabolism of chylomicrons and very-low-density lipoproteins (VLDL). The physiological role of HTGL is less certain. HTGL has been postulated to be an alternate enzyme to LPL in hydrolysis of triglyceride in VLDL and to be an important enzyme for removal of phospholipid from both low-density lipoproteins (LDL) and high-density lipoproteins (HDL). In this latter role, this enzyme would convert larger, lighter lipoprotein particles to smaller denser particles. HTGL deficiency has been found in severe liver disease and with a genetic deficiency of this enzyme. A unique patient is described with acquired hepatic triglyceride lipase deficiency and vitamin A intoxication. This patient developed hypercholesterolemia with an increase in both LDL and HDL. An increased proportion of lighter LDL (LDL1) and HDL (HDL2) was noted. In addition, after administration of heparin there was no shift in the distribution of apoE in plasma fractionated using a column containing 4% agarose. These findings are consistent with a postulated role of HTGL in metabolism of light LDL and HDL particles and some classes of apoE containing lipoproteins.     

A selective decline of postheparin plasma hepatic triglyceride lipase in hypothyroid rats

The present study aimed to define the effect of thyroid status on two postheparin plasma lipases, i.e., lipoprotein lipase and hepatic triglyceride lipase. Rats with hypo- and hyperthyroidism were used for this purpose. Separate measurement of these two lipases was done by an immunochemical method utilizing antiserum specific to hepatic triglyceride lipase. The 5-wk thyroidectomized, hypothyroid rats had normal plasma concentrations of both triglyceride and cholesterol. These rats showed a selective decline in the activity of postheparin plasma hepatic triglyceride lipase with normal lipoprotein lipase activity. The rats made thyrotoxic by thyroxine treatment had normal plasma levels of both triglyceride and cholesterol. These rats showed normal activities of both hepatic triglyceride lipase and lipoprotein lipase. The observed finding of a selective decline of hepatic triglyceride lipase in hypothyroid rats is discussed in connection with the possible function of this enzyme in lipoprotein metabolism.     

Effect of sucrose overfeeding on brown adipose tissue lipogenesis and lipoprotein lipase activity in rats

During cold-induced nonshivering thermogenesis, interscapular brown adipose tissue (BAT) lipoprotein lipase (LPL) activity and lipogenesis are elevated. Because of the many similarities between cold- and diet-induced thermogenesis, we examined the effect of ad libitum access to a 32% sucrose solution on caloric intake, adiposity, and BAT enzyme activities in male rats. Daily caloric intakes of sucrose-fed animals were elevated by 20%-25%, and 8 wk of sucrose feeding doubled carcass fat content. This sucrose-feeding induced obesity was associated with increases in circulating triglyceride and insulin levels as well as increased retroperitoneal white adipose tissue LPL activity. However, the increased carcass lipid content accounted for less than half of the excess calories ingested by the sucrose-fed rats. Sucrose feeding stimulated in vivo lipogenesis in BAT and elevated BAT fatty acid synthetase and acetyl-CoA carboxylase activities but not LPL activity. These findings suggest that overeating enhances endogenous lipogenesis but not uptake of circulating triglyceride in BAT. Thus, both cold- and diet-induced thermogenesis increase BAT lipogenesis, while only cold-induced thermogenesis is associated with elevated LPL activity in BAT.     

Effects of pregnancy, postpartum lactation, and oral contraceptive use on the lipoprotein cholesterol/triglyceride ratio

Lipoprotein cholesterol/triglyceride ratio changes have been observed previously with sex hormone use. To determine if the lipoprotein cholesterol/triglyceride ratio is similarly changed by pregnancy and postpartum lactation, we examined pregnant subjects at 36 weeks gestation and the same women at 6 weeks postpartum and compared them to age-matched, nonpregnant women using or not using oral contraceptives. The cholesterol/triglyceride ratios were examined as means and medians and as curvilinear functions of increasing triglyceride concentration. Median ratios did not predict all ratio changes identified graphically. At very-low-density lipoprotein (VLDL) triglyceride concentrations below 40 mg/dL, the VLDL ratio is less than control in oral contraceptive users and further reduced in pregnant women. Above triglyceride concentrations of 40-60 mg/dL, the curves in the three groups are indistinguishable. No effect of lactation is observed. The low-density lipoprotein (LDL) cholesterol/triglyceride ratio is comparably lower in pregnant subjects and oral contraceptive users at all concentrations of lipoprotein triglyceride and again there is no effect of lactation. In high-density lipoprotein (HDL), there is no effect of either pregnancy or oral contraceptive use on the cholesterol/triglyceride ratio, while it is significantly higher with lactation. Postpartum decreases in the VLDL and LDL cholesterol/triglyceride ratio are seen at all lipoprotein concentrations independent of lactation. We conclude that triglyceride enriches VLDL at low concentrations and LDL at all concentrations in pregnancy and with oral contraceptive use, suggesting a common, hormonal mechanism. HDL is enriched with cholesterol during postpartum lactation, consistent with decreased transfer of cholesterol to other lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of streptozotocin diabetes on hepatic triglyceride lipase activity in the rat

The function of the hepatic triglyceride lipase (H-TGL) is not yet clear. The purpose of the present study was to investigate the possible hormonal regulation of H-TGL. Postheparin plasma was obtained 3 min after the intravenous injection of 50 U/250 g body weight of heparin into male Wistar rats. The lipase activities were measured using substrate containing [¹⁴C] triolein emulsified with gum arabic and were expressed in μmoles of free fatty acid released/ml/hour (mean ± SD). H-TGL was the lipase activity remaining after inhibition of lipoprotein lipase (LPL) by 1.0 M NaCl. Diabetic rats were prepared by intravenous injection of streptozotocin (STZ), 65 mg/kg body weight. The contributions of H-TGL and LPL to the total plasma triacylglycerol hydrolase (TGH) activity depend on the amount of heparin injected and the time of blood withdrawal after heparin injection. H-TGL was maximally released at higher heparin (50 U/250 g body weight) concentrations, compared to LPL which was maximally released at lower heparin (5 U/250 g body weight) concentrations. H-TGL was significantly higher at 3 min after the injection of 50 U of heparin/250 g body weight than at 20 min. Twenty-four-hour fasting produced a significant fall in H-TGL compared to H-TGL in fed rats. Total TGH was significantly lower in diabetic rats 3 days after STZ injection. In diabetic rats 3, 5, and 7 days after STZ injection, H-TGL were significantly lower than those in control rats. H-TGL and H-TGL/total TGH were 9.49 ± 0.99 and 0.551 ± 0.071, respectively, in rats 3 days after STZ injection, compared to H-TGL (13.46 ± 0.69) and H-TGL/total TGH (0.739 ± 0.052) in control nondiabetic rats. When diabetic rats were treated with insulin, total TGH (14.37 ± 3.01) and H-TGL (6.77 ± 4.12) rose to 25.16 ± 1.02 (total TGH) and 16.46 ± 1.13 (H-TGL), that were comparable to activities in control nondiabetic rats. Separation of H-TGL and LPL was performed using heparin-Sepharose affinity chromatography of postheparin plasma. The enzyme activity of peak I from STZ rats, which is eluted by 0.72 M NaCl-Veronal buffer, pH 7.4 and corresponds to H-TGL, was approximately half the activity from control rats. TGH released by heparin from isolated rat liver parenchymal cells was investigated. The enzyme activities released from isolated liver parenchymal cells prepared from STZ rats was approximately half that from control rats. The role of insulin in the regulation of LPL has been well documented. Our findings suggest that H-TGL also is under hormonal regulation by insulin in rats.     

Impaired very low density lipoprotein and triglyceride removal in broad beta disease: comparison with endogenous hypertriglyceridemia.

The removal rate of apoprotein-B (apo B) in very low density lipoprotein (VLDL) was decreased in individuals with broad beta disease when compared with endogenous hypertriglyceridemia. Following the injection of 125I-VLDL isolated from individuals with endogenous hypertriglyceridemia, both VLDL apo B fractional catabolic rate (0.058 +/- 0.029 hr-1) and VLDL apo-B turnover rate (0.300 +/- 0.070 mg/kg/hr) were lower in broad beta disease than in endogenous hypertriglyceridemia (fractional catabolic rate 0.112 +/- 0.046, p less than .05; turnover rate 0.640 +/- 0.199, p less than .005) despite equivalent plasma concentrations of VLDL-apo-B. Furthermore, conversion of VLDL apo-B to LDL was impaired in broad beta disease relative to endogenous hypertriglyceridemia. Differences in the kinetics of lipoprotein lipase-related triglyceride removal during a maximal heparin infusion were also demonstrated between these two disorders. These differences suggest an abnormality in the interaction of lipoprotein lipase with the lipoproteins of unusual composition in broad beta disease. This is further supported by the normalization of lipoprotein composition in broad beta disease by estrogen therapy, with a simultaneous change in the kinetics of lipoprotein lipase-related triglyceride removal towards those seen in endogenous hypertriglyceridemia.     

Adipose tissue lipoprotein lipase activity in type III hyperlipoproteinemia.

An impairment in the catabolism of chylomicron and very low density lipoprotein remnants appears to cause the lipid abnormalities in type III hyperlipoproteinemia. A reduction in the activity of lipoprotein lipase (LPL) has been suggested as the catabolic defect. Results in this study indicate that the activity of adipose tissue LPL measured in the fasted and fed states are in the normal range in type III hyperlipoproteinemia (fasted: type III = 2.7 +/- 1.8 mU/10(6) cells, N = 8; normals = 3.4 +/- 2.5, N = 23, p, not significant; fed: type III = 3.6 +/- 2.1, N = 7; normals = 4.8 +/- 1.8, N = 12, p, not significant). This suggests that perhaps another mechanism, such as the interaction between LPL and its lipid substrate, is abnormal, or that the activity of LPL derived from another tissue source is deficient.     

Availability of apolipoprotein CII in relation to the maximal removal capacity for an infused triglyceride emulsion in man.

The aim of this study was to evaluate whether the transfer to triglyceride-rich particles of apolipoprotein CII is a quantitative determinant of triglyceride removal. An emulsion of triglyceride, Intralipid, which resembles chylomicrons in particle size but does not contain apolipoprotein, was infused at a constant rate for 1 hr in ten subjects with plasma triglyceride levels ranging from 40 to 636 mg/dl. During the infusion, samples were taken for measurement of particulate triglyceride by nephelometry and quantification of apolipoprotein content by polyacrylamide gel electrophoresis of reisolated particles. The maximal removal capacity for Intralipid-triglyceride, calculated as the infusion rate minus the linear increase in plasma Intralipid-triglyceride, was inversely related to the basal plasma triglyceride level. The apolipoproteins bound to Intralipid were apo CI, CII, and CIII. Apo A and apo E were not detected. The $\text{CII}\text{CIII}$ ratio was higher in larger triglyceride-rich particles (Intralipid) than in smaller ones (VLDL and HDL). The $\text{CII}\text{CIII}$ ratio in VLDL isolated before infusion was higher than in VLDL isolated 2 min after starting infusion. The amount of apolipoprotein CII bound to infused Intralipid increased in parallel to the increase in triglyceride level, with a constant $\text{CII}\text{TG}$ ratio between 2 and 60 min. The maximal removal capacity for infused Intralipid-triglyceride was not quantitatively related to the CII binding, expressed as $\text{CII}\text{TG}$. It is concluded that (1) the transfer of apolipoprotein CII from HDL, and also from VLDL, to large triglyceriderich emulsion particles entering the circulation occurs within minutes; (2) the availability of apolipoprotein CII for binding to continuously entering Intralipid particles is unlimited during 1 hr; (3) the amount of apolipoprotein CII bound does not control the rate of Intralipid-triglyceride removal from the plasma.     

Pathophysiology of lipoprotein transport.

A system for classification of genetic and acquired forms of hyperlipidemia in humans based on lipoprotein physiology is described. Most hyperlipidemia can be accounted for by defects in one of four sites of physiologic regulation: (1) triglyceride-rich lipoprotein production, (2) lipoprotein lipase-mediated triglyceride catabolism, (3) remnant lipoprotein catabolism, and (4) extrahepatic cholesterol-rich lipoprotein catabolism.     

Low density lipoprotein receptor activity in freshly isolated human blood monocytes and lymphocytes

Circulating human monocytes and lymphocytes were isolated by counterflow and density gradient centrifugation. Binding and degradation of low density lipoprotein (LDL) occurred predominantly in monocytes and to a much lesser extent in lymphocytes. The findings are consistent with greater LDL receptor activity in freshly isolated monocytes than lymphocytes, in keeping with differences in other cell surface receptors between these two cell types. Therefore, when freshly isolated mixed mononuclear cells are used to study LDL receptor activity in vivo in humans, careful attention needs to be given to the proportions of monocytes and lymphocytes, or alternatively, relatively pure preparations of monocytes should be used.     

Reduction of plasma triglyceride concentration by acute stress in man.

Three different forms of stress all resulted in acute reduction of plasma triglyceride concentrations. Pyrogen reactions in two hypertriglyceridemic men resulted in the lowering of very-low-density lipoprotein (VLDL) triglyceride levels by 93% and 73% due to decreased secretion of this lipoprotein into plasma. More modest reductions in plasma triglycerides were observed after 2-deoxyglucose-induced intracellular glucopenia and insulin-induced hypoglycemia. With hypoglycemia, the lowering of plasma triglyceride concentration correlated significantly with the stimulation of urinary epinephrine output (r = 0.86) but with neither the urinary norepinephrine response nor with the increase in plasma immunoreactive glucagon levels. To further test whether these changes in plasma triglyceride levels were mediated via the sympathetic nervous system, hypoglycemia was evoked by insulin in subjects with traumatic spinal cord transactions. Two such subjects, who demonstrated sympathetic stimulation in response to hypoglycemia, had evidence of reduced VLDL secretion into plasma, while in two who had no evidence of an adrenergic response. VLDL secretion was not inhibited. Thus, acute lowering of plasma triglyceride concentrations by certain forms of stress appears to be mediated via the sympathetic nervous system.     

Abnormal lipoprotein-lipase-mediated plasma triglyceride removal in untreated diabetes mellitus associated with hypertriglyceridemia.

Hypertriglyceridemia is common in untreated diabetes mellitus. An abnormality in the interaction of lipoprotein lipase with endogenous circulating plasma lipoprotein triglyceride has been demonstrated in untreated diabetes. These diabetics have a decreased maximal removal capacity for plasma triglyceride (27.0 mg TG/kh/hr) and increased Km (390 mg/dl) for endogenous plasma triglyceride-lipoprotein lipase interaction compared to that found in nondiabetic hypertriglyceridemic subjects (Vmax, 32.0; km, 157). Diabetics treated for at least two months have a maximal removal capacity and Km similar to that of nondiabetic subjects (Vmax, 32.7; Km, 192). No evidence for an increase in triglyceride production due to diabetes per se was found. When diabetic subjects with triglyceride levels over 400 mg/dl were selected for study, most were found to have an independent familial form of hypertriglyceridemia.     

Hepatic triglyceride lipase in diabetic dogs

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.