Characterization of insulin binding to isolated swine adipocytes.

The objectives of this study were to determine if binding sites for insulin were present on isolated swine adipocytes and to characterize insulin receptors in terms of kinetics and specificity if they existed. The binding of purified porcine [125I]iodoinsulin to isolated adipocytes at 30 C was rapid, achieving a steady state within 45 min that was maintained for 2 h. Specific binding of [125I]iodoinsulin tracer was 2.5-3.0% for 2 X 10(5) cells/ml after 2h. Competition for binding was observed with half-maximal displacement of [125I]iodoinsulin at insulin concentrations of 4.2 X 10(-10) M. Porcine proinsulin was 16-fold less potent that insulin in displacing [125I]iodoinsulin from receptor sites. Glucagon did not cause displacement of [125I]iodoinsulin. Scatchard analysis of the data from competitive binding studies indicated the presence of two classes of binding sites. The Ka was approximately 4.5 X 10(9) M-1 for high affinity sites and approximately 2.1 X 10(-8) M-1 for low affinity sites. These findings indicate that 1) receptors which specifically bind insulin are present on swine adipocytes and 2) the affinity and number of the two classes of binding sites are similar to those of adipocytes isolated from the rat, a species in which insulin elicits a much greater in vitro stimulatory effect on glucose metabolism than previously observed for swine adipocytes.

Characterization of porcine growth hormone (pGH) binding to porcine liver microsomes: chronic administration of pGH induces pGH binding.

The effect that GH has on regulating GH binding to its receptors has not been resolved. This report describes the characterization of porcine (p) GH binding to pig liver membranes and clarifies the issue of regulation of GH binding by measuring pGH binding to liver membranes prepared from pigs treated daily for 35 days with different doses of pGH (0, 10, 30, or 70 micrograms/kg BW). Specific binding of [125I]pGH was dependent on time, pH, and membrane protein concentration. At 23 C, pGH binding reached a steady state after 24 h. Maximal pGH binding was observed at pH 7. Binding increased linearly as membrane protein concentration was increased from 150 to 450 micrograms/tube. Specificity studies indicated that the hepatic GH receptor was somatogenic, since porcine PRL poorly inhibited [125I] pGH binding (cross-reactivity, 0.1%). Treatment of microsomes from control pigs with 4 m MgCl2 to remove endogenously bound pGH did not affect pGH binding, whereas binding was significantly increased to microsomes from pGH-treated pigs. Binding of pGH increased in a linear manner with the dose of pGH given for 35 days (r = 0.79), thus establishing the inductive effect of chronic pGH administration on pGH binding in pig liver. GH binding was highly correlated with weight gain in pigs treated with pGH (r = 0.76). In addition, the serum insulin-like growth factor I (IGF-I) concentration was increased linearly (r = 0.87) by pGH. This increase in serum IGF-I was also highly correlated with the increase in pGH binding (r = 0.71). These results suggest that hepatic GH binding plays an important role in regulating pig growth, which may be mediated, in part, by an increase in hepatic IGF-I synthesis and secretion. The present report is also the first to establish that exogenous pGH induces pGH binding to pig hepatic GH receptors and to relate this increase in binding to an enhancement in pig growth.

Preparation of isolated bovine adipocytes: validation of use for studies characterizing insulin sensitivity and binding.

The present study was undertaken to develop techniques to isolate bovine adipocytes, to compare their rates of glucose metabolism and insulin sensitivity with adipocytes in adipose tissue, and to determine if isolated bovine adipocytes specifically bind insulin. Cell size and diameter distributions were the same for adipocytes fixed with OsO4 after isolation with collagenase and adipocytes liberated from OsO4-fixed adipose tissue slices. On a per cell basis, lipogenic rates were greater for isolated adipocytes compared with intact adipose tissue. Similar differences were found for glucose oxidation. In short term incubations, glucose oxidation and lipid synthesis were not stimulated by insulin (0-100 ng/ml) in either isolated adipocytes or tissue. Specific binding of [125I]iodoinsulin at 30 C was low (0.8%) in the first group of six beef cattle sampled, but increased with increasing cell concentration. Insulin degradation after 90 min was less than 5%. The specificity of [125I]iodoinsulin binding was studied in a second group of six animals. There was no specific binding of insulin in this group. In summary, bovine adipocytes can be isolated which are metabolically active and provide a valid system for studying hormone binding and action. In the present study, glucose metabolism in bovine adipocytes was not stimulated by insulin in vitro. This insensitivity to insulin was associated with a negligible capacity for insulin binding. These findings suggest that the lack of insulin sensitivity in bovine adipose tissue may be due to an inability to specifically bind insulin. This may be related to the unique metabolism of ruminant adipose tissue, which is less dependent upon glucose for fatty acid synthesis than is adipose tissue from nonruminant species.

Antagonism of insulin action in cultured pig adipose tissue by pituitary and recombinant porcine growth hormone: potentiation by hydrocortisone.

The effects of physiological levels of pituitary porcine GH (ppGH) and recombinant pGH (rpGH) on lipogenesis in pig adipose tissue incubated with insulin and hydrocortisone (HC) were measured in short term (2-h) incubations and after long term culture (50 h). HC (50 ng/ml) had no effect on lipogenesis in 2-h incubations; however, HC and insulin (10 ng/ml) maintained the lipogenic capacity of cultured tissue at rates comparable to those in fresh adipose tissue. Neither ppGH nor rpGH (1 and 10 ng/ml, respectively) had any effect in short term incubations. After 50 h of culture, ppGH and rpGH both directly antagonized the ability of insulin to maintain lipogenesis; however, this antagonism was markedly enhanced by HC. The present study is the first to demonstrate a direct antagonism of insulin action by ppGH and rpGH in pig adipose tissue, and a marked potentiation of this antagonism by HC. This intrinsic property of pGH may account, in part, for the decrease in adipose tissue growth rates in pigs treated chronically with pGH.

Native and recombinant bovine growth hormone antagonize insulin action in cultured bovine adipose tissue.

The current study was undertaken to determine if pituitary bovine GH (pbGH) and recombinant bGH (rbGH) antagonized insulin action in bovine adipose tissue after acute (2-h) and chronic (48-h) exposure and whether this was an intrinsic property of bGH. Insulin action (measured as the effect on incorporation of acetate-carbon into long-chain fatty acids) was unaffected by bGH in short term incubations regardless of whether hydrocortisone (HC) was present. After 48 h of culture, however, both pbGH and rbGH similarly antagonized the ability of insulin to maintain lipogenic capacity. This antagonism was dependent upon the presence of HC and was dose dependent, with half-maximal inhibition of insulin action occurring at about 0.5 ng/ml bGH. Bovine PRL did not mimic the effects of bGH on insulin action. These results establish that bGH antagonizes insulin action in bovine adipose tissue and that this effect is dependent upon long term exposure and the inclusion of HC in the culture medium. The fact that both rbGH and pbGH acted similarly indicates that this is an intrinsic property of bGH. The effect of bGH on insulin-dependent maintenance of lipogenic capacity may play an important role in redirecting nutrients away from adipose tissue to other tissues, such as muscle or mammary tissue. It is speculated that this metabolic effect of bGH plays an important role in the adaptive response to chronic bGH treatment, which increases milk yield of dairy cows and growth performance of beef cattle.

Ontogeny of insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in porcine serum during fetal and postnatal development.

The insulin-like growth factors (IGF-I and IGF-II) circulate in plasma in association with IGF-binding proteins (IGFBPs). As a first step to understanding the regulation of expression of these proteins in pigs, we characterized the ontogeny of circulating IGFs and IGFBPs during fetal and early postnatal development. Serum IGFs were separated from IGFBPs, before IGF RIA, by acidification and chromatography on C18 Sep-Pak cartridges. The IGF-I levels increased during the latter half of fetal life from 11 +/- 1 ng/ml on day 60 to 37 +/- 3 ng/ml on day 112 (2-3 days before term) and further increased postnatally to 227 +/- 21 to 265 +/- 26 ng/ml) and also increased higher than IGF-I levels, with no obvious developmental pattern, during fetal life (170 +/- 21 to 265 +/- 26 ng/ml) and also increased postnatally by 2-fold (463 +/- 29 ng/ml on day 42). These results support the view that IGF-II is a fetal and postnatal growth factor, whereas IGF-I is primarily a postnatal growth mediator in pigs. Serum IGF-binding proteins were identified by Western ligand blotting. Five IGFBPs with apparent mol wt of 43K, 39K, 34K, 31K, and 26K were detected in fetal and postnatal sera. The two largest proteins were shown to be glycoproteins and immunologically related to porcine (p) IGFBP-3, suggesting that they are glycosylation variants of pIGFBP-3. The abundance of these two IGFBPs increased coincidently with increasing serum IGF-I levels. The 34K IGFBP was immunologically related to rIGFBP-2 and was 2- to 3-fold more abundant in fetal serum than in postnatal serum. The 31K IGFBP was resolved into a triplet and also was a component of pIGFBP-3 immunoprecipitates. Similarly, the 26K IGFBP was present in pIGFBP-3 immunoprecipitates. The 31K and 26K IGFBPs represented a minor portion of serum IGF-binding activity in fetal and postnatal pigs and exhibited no obvious developmental patterns. It is hypothesized that the postnatal increases in serum IGF-I and 43K and 39K IGFBPs as well as the decrease in the 34K IGFBP are driven by GH action.

Clinical review 21: The efficacy and safety of growth hormone for animal agriculture.

Public understanding, perception, and acceptance are important for the benefits of biotechnology to be realized. Based upon sound scientific evidence, GH does not appear to pose any risk to the consumer. More than 1000 papers have been published about bGH and pGH, and the principal lines of evidence supporting the position that they are safe are reviewed herein. Recently, an independent committee appointed by The National Institutes of Health examined the available data and concluded that "The evidence clearly indicates that the overall composition and nutritional quality of milk and meat from bGH-treated cows is equal to that from untreated cows". Similarly, the FDA has concluded that the use of bGH presents no increased health risk to consumers. In addition, there is compelling evidence to indicate that GH poses no increased health risk to the target animal. Thus, GH treatment of farm animals is not only an effective technology for increasing productive efficiency but one that poses no increased health risk for either the consumer or the target animal.

Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic.

In the present study we used regression analyses to evaluate the effects of stearic acid (18:0) on total cholesterol (TC), low-density-lipoprotein-cholesterol (LDL-C), and high-density-lipoprotein-cholesterol (HDL-C) concentrations (mmol/L). Using data from 18 articles, we developed the following predictive equations (monounsaturated fatty acids, MUFAs; polyunsaturated fatty acids, PUFAs): delta TC = 0.0522 delta 12:0-16:0 - 0.0008 delta 18:0 - 0.0124 delta MUFA - 0.0248 delta PUFA; delta LDL-C = 0.0378 delta 12:0-16:0 + 0.0018 delta 18:0 - 0.0178 delta MUFA - 0.0248 delta PUFA; delta HDL-C = 0.0160 delta 12:0-16:0 - 0.0016 delta 18:0 + 0.0101 delta MUFA + 0.0062 delta PUFA. Our analyses revealed that unlike the other long-chain saturated fatty acids (SFAs), stearic acid had no effect on TC and lipoprotein cholesterol concentrations in men and women. MUFAs elicited an independent hypocholesterolemic effect that we believe is due to the small amount of 12:0-16:0 in the experimental diets evaluated. The observation that stearic acid has unique effects on TC, LDL-C, and HDL-C provides additional compelling evidence that it be distinguished from the other major SFAs in blood cholesterol predictive equations.

Mechanisms by which somatotropin decreases adipose tissue growth.

When growing pigs are treated daily with recombinantly derived porcine somatotropin (pST) for 30-60 d there is a dose-dependent decrease in lipid accretion. Maximal doses of pST can reduce lipid accretion by as much as 70%. The reduction in lipid accretion occurs because of a marked decrease in glucose transport and lipogenesis that is the result of a pST-dependent decrease in the ability of insulin to stimulate these processes in the adipocyte; lipolysis is not affected. The decrease in insulin sensitivity is not due to a decrease in insulin binding or insulin receptor kinase activity. Little is understood about the somatotropin (ST) intracellular signal pathway(s) that mediate the biological effects of ST. These effects are chronic rather than acute as was previously believed. This pattern likely reflects that ST decreases transcription of important insulin-responsive genes such as the muscle-adipose tissue transporter gene (GLUT4) and key lipogenic enzymes.

Plasma lipids and diet of the Mvskoke Indians.

Plasma lipids, lipoproteins, and apolipoproteins were measured in 123 female and 57 male Mvskoke Indians, a population of American Indians with a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). Dietary patterns were assessed with a food-frequency questionnaire. There were no differences in total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), apolipoproteins A-I or B in female Indians with and without diabetes. In males with diabetes, however, LDL-C was lower. Triglyceride and fasting plasma glucose were higher in subjects with diabetes. Total cholesterol and LDL-C were lower and HDL-C was higher than age and sex-matched Lipid Research Clinics values, especially for subjects with diabetes. This is surprising given that the diet of Mvskoke Indians contains foods high in total fat, saturated fatty acids, and cholesterol. We may explain, in part, the low incidence of coronary heart disease in this population.

Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans.

BACKGROUND: Flavonoids are polyphenolic compounds of plant origin with antioxidant effects. Flavonoids inhibit LDL oxidation and reduce thrombotic tendency in vitro. Little is known about how cocoa powder and dark chocolate, rich sources of polyphenols, affect these cardiovascular disease risk factors. OBJECTIVE: We evaluated the effects of a diet high in cocoa powder and dark chocolate (CP-DC diet) on LDL oxidative susceptibility, serum total antioxidant capacity, and urinary prostaglandin concentrations. DESIGN: We conducted a randomized, 2-period, crossover study in 23 healthy subjects fed 2 diets: an average American diet (AAD) controlled for fiber, caffeine, and theobromine and an AAD supplemented with 22 g cocoa powder and 16 g dark chocolate (CP-DC diet), providing approximately 466 mg procyanidins/d. RESULTS: LDL oxidation lag time was approximately 8% greater (P = 0.01) after the CP-DC diet than after the AAD. Serum total antioxidant capacity measured by oxygen radical absorbance capacity was approximately 4% greater (P = 0.04) after the CP-DC diet than after the AAD and was positively correlated with LDL oxidation lag time (r = 0.32, P = 0.03). HDL cholesterol was 4% greater after the CP-DC diet (P = 0.02) than after the AAD; however, LDL-HDL ratios were not significantly different. Twenty-four-hour urinary excretion of thromboxane B(2) and 6-keto-prostaglandin F(1)(alpha) and the ratio of the 2 compounds were not significantly different between the 2 diets. CONCLUSION: Cocoa powder and dark chocolate may favorably affect cardiovascular disease risk status by modestly reducing LDL oxidation susceptibility, increasing serum total antioxidant capacity and HDL-cholesterol concentrations, and not adversely affecting prostaglandins.

Polyunsaturated fatty acids in the food chain in the United States.

In the United States, intake of n-3 fatty acids is approximately 1.6 g/d ( approximately 0.7% of energy), of which 1.4 g is alpha-linolenic acid (ALA; 18:3) and 0.1-0.2 g is eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6). The primary sources of ALA are vegetable oils, principally soybean and canola. The predominant sources of EPA and DHA are fish and fish oils. Intake data indicate that the ratio of n-6 to n-3 fatty acids is approximately 9.8:1. Food disappearance data between 1985 and 1994 indicate that the ratio of n-6 to n-3 fatty acids has decreased from 12.4:1 to 10.6:1. This reflects a change in the profile of vegetable oils consumed and, in particular, an approximate 5.5-fold increase in canola oil use. The ratio of n-6 to n-3 fatty acids is still much higher than that recommended (ie, 2.3:1). Lower ratios increase endogenous conversion of ALA to EPA and DHA. Attaining the proposed recommended combined EPA and DHA intake of 0.65 g/d will require an approximately 4-fold increase in fish consumption in the United States. Alternative strategies, such as food enrichment and the use of biotechnology to manipulate the EPA and DHA as well as ALA contents of the food supply, will become increasingly important in increasing n-3 fatty acid intake in the US population.

Nuts and their bioactive constituents: effects on serum lipids and other factors that affect disease risk.

Because nuts have favorable fatty acid and nutrient profiles, there is growing interest in evaluating their role in a heart-healthy diet. Nuts are low in saturated fatty acids and high in monounsaturated and polyunsaturated fatty acids. In addition, emerging evidence indicates that there are other bioactive molecules in nuts that elicit cardioprotective effects. These include plant protein, dietary fiber, micronutrients such as copper and magnesium, plant sterols, and phytochemicals. Few feeding studies have been conducted that have incorporated different nuts into the test diets to determine the effects on plasma lipids and lipoproteins. The total- and lipoprotein-cholesterol responses to these diets are summarized in this article. In addition, the actual cholesterol response was compared with the predicted response derived from the most current predictive equations for blood cholesterol. Results from this comparison showed that when subjects consumed test diets including nuts, there was an approximately 25% greater cholesterol-lowering response than that predicted by the equations. These results suggest that there are non-fatty acid constituents in nuts that have additional cholesterol-lowering effects. Further studies are needed to identify these constituents and establish their relative cholesterol-lowering potency.

High-monounsaturated fatty acid diets lower both plasma cholesterol and triacylglycerol concentrations.

BACKGROUND: Low-fat diets increase plasma triacylglycerol and decrease HDL-cholesterol concentrations, thereby potentially adversely affecting cardiovascular disease (CVD) risk. High-monounsaturated fatty acid (MUFA), cholesterol-lowering diets do not raise triacylglycerol or lower HDL cholesterol, but little is known about how peanut products, a rich source of MUFAs, affect CVD risk. OBJECTIVE: The present study compared the CVD risk profile of an Average American diet (AAD) with those of 4 cholesterol-lowering diets: an American Heart Association/National Cholesterol Education Program Step II diet and 3 high-MUFA diets [olive oil (OO), peanut oil (PO), and peanuts and peanut butter (PPB)]. DESIGN: A randomized, double-blind, 5-period crossover study design (n = 22) was used to examine the effects of the diets on serum lipids and lipoproteins: AAD [34% fat; 16% saturated fatty acids (SFAs), 11% MUFAs], Step II (25% fat; 7% SFAs, 12% MUFAs), OO (34% fat; 7% SFAs, 21% MUFAs), PO (34% fat; 7% SFAs, 17% MUFAs), and PPB (36% fat; 8% SFAs, 18% MUFAs). RESULTS: The high-MUFA diets lowered total cholesterol by 10% and LDL cholesterol by 14%. This response was comparable with that observed for the Step II diet. Triacylglycerol concentrations were 13% lower in subjects consuming the high-MUFA diets and were 11% higher with the Step II diet than with the AAD. The high-MUFA diets did not lower HDL cholesterol whereas the Step II diet lowered it by 4% compared with the AAD. The OO, PO, and PPB diets decreased CVD risk by an estimated 25%, 16%, and 21%, respectively, whereas the Step II diet lowered CVD risk by 12%. CONCLUSION: A high-MUFA, cholesterol-lowering diet may be preferable to a low-fat diet because of more favorable effects on the CVD risk profile.

The growth hormone-dependent decrease in hepatic fatty acid synthase mRNA is the result of a decrease in gene transcription.

The present study was conducted to determine the chronic effects of porcine growth hormone administration on fatty acid synthase (FAS) mRNA abundance and gene transcription in growing rats. Growth hormone treatment increased growth rate approximately 27% (P<0.01). Porcine growth hormone decreased FAS mRNA levels by 55%. The reduction in FAS mRNA was due to a marked decrease in transcription of the FAS gene (decreased by 80%). In contrast, porcine growth hormone did not affect mRNA abundance or transcription rate of another insulin-regulated gene, phosphoenolpyruvate carboxykinase. In summary, our results have established that chronic treatment with growth hormone decreases FAS mRNA by decreasing the transcription rate of the gene. Furthermore, they suggest that the effects of growth hormone are specific and are not mediated by general changes in insulin-responsive gene expression in liver.

Effects of porcine growth hormone and insulin-like growth factor-I (IGF-I) on immunoreactive IGF-binding protein concentration in pigs.

A specific radioimmunoassay (RIA) was established for an acid-stable insulin-like growth factor-binding protein (IGF-BP) isolated from porcine serum. The RIA recognizes a GH-dependent 150 kDa protein in porcine serum; therefore we postulate that the acid-stable IGF-BP is a component of the high molecular weight IGF-BP in porcine serum. The IGF-BP concentration was assayed in porcine serum (normal, 2.44 mg/l; hypophysectomized, 0.83 mg/l; serum from a GH-treated pig, 4.72 mg/l), porcine colostrum (2.55 mg/l), milk (0.91 mg/l), and amniotic (1.82-3.14 mg/l), allantoic (2.94-3.58 mg/l) and follicular (2.28 mg/l) fluids. Serum concentrations of IGF-BP were significantly increased (63%) in pigs chronically injected with porcine GH (pGH) (70 micrograms/kg body weight per day for 17 days). Concentrations of IGF-BP did not change in porcine serum following acute challenges with pGH (10-1000 micrograms/kg body weight) or IGF-I (4 or 8 mg per pig). This is the first report of a specific RIA for the porcine GH-dependent IGF-BP. Our results indicate that this IGF-BP is found in a wide variety of biological fluids and that its concentration appears to be regulated by pGH but not by IGF-I.

Changes in serum concentrations of ACTH, corticosterone and in growth following morning or evening injection of female rats with porcine growth hormone.

The present study was designed to examine the effects of stress, associated with daily handling and placebo injection, on growth and adrenal activity in female rats. A second objective was to examine the effects of porcine GH (pGH) on growth and on serum concentrations of ACTH and corticosterone. Treatments were administered in the morning (08.00 h) in semi-darkness, or in the evening (20.00 h) towards the end of the light period and were timed to coincide with reported periods of high and low adrenal sensitivity to ACTH. Handling of and s.c. injection of saline into female rats (initial body weight 220 g) each morning for 21 days did not affect growth, food intake or organ weights. In contrast, daily handling and saline injection each evening caused a marked reduction in weight gain (25%), food intake (12%) and liver weight (8%), accompanied by a trend towards an increase in adrenal weight (11%), but no change in serum corticosterone concentrations. In a second experiment, treatment of female rats (initial body weight 180 g) with pGH (5.6 mg/kg) daily at 08.00 h caused a significant improvement in weight gain (17%), but food intake and organ weights were unaltered. Daily injection of rats with pGH at 20.00 h caused a greater relative improvement in weight gain (45%) than did treatment at 08.00 h as the growth impairment caused by the stress of handling was counteracted. The adverse effect of evening injections of saline on food intake was also counteracted by pGH. Changes in liver and adrenal weights, however, were not attenuated by pGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of exogenous porcine growth hormone on serum insulin-like growth factor-binding proteins in growing pigs.

The insulin-like growth factor-binding proteins (IGFBPs) in sera of growing pigs were partially characterized with respect to their size, immunological relationships to other known IGFBPs and their regulation by porcine (p) GH. Castrated male pigs (14-16 weeks of age) were treated with either vehicle or pGH (up to 100 micrograms/kg body weight per day) by daily i.m. injection for 7 days. Blood samples were collected by jugular venepuncture at the time of injection. Five IGFBPs of 43, 40, 34, 30 and 26 kDa were identified on ligand blots of porcine sera. A 30 kDa IGFBP, in addition to the 43 and 40 kDa IGFBPs, was immunoprecipitated by antiserum to pIGFBP-3 and found to contain N-linked carbohydrate suggesting that it is a fragment of pIGFBP-3 as has been noted for a 29 kDa N-glycosylated IGFBP in rat sera. The 34 kDa IGFBP in pig sera was precipitated by antisera to rat IGFBP-2 and contained no N-linked carbohydrate. Administration of pGH to normal growing pigs not only increased pIGFBP-3 levels but elicited a dose-dependent suppression of levels of the 34 kDa IGFBP as well. In summary, the Mr pattern of IGFBPs in the sera of growing pigs is similar to that observed in fetal and maternal pig sera and in other species. Furthermore, we report that administration of pGH to normal pigs suppresses the expression of an IGFBP-2-like IGFBP in pig sera while increasing expression of pIGFBP-3.

An acid-stable insulin-like growth factor (IGF)-binding protein from pig serum inhibits binding of IGF-I and IGF-II to vascular endothelial cells.

The effects of a porcine insulin-like growth factor (IGF)-binding protein on binding of IGF-I and IGF-II to porcine aortic endothelial cells (PAEC) were determined. Binding of 125I-labelled IGF-I and -II to IGF receptors was inhibited by IGF-binding protein. IGF-binding protein inhibited binding of IGF-I and -II in a dose-dependent manner with half-maximal inhibition occurring at 5.43 and 108 micrograms/l respectively. A 125I-labelled IGF-I--IGF-binding protein complex, formed by incubating 125I-labelled IGF-I with IGF-binding protein overnight at 4 degrees C, did not effectively bind to endothelial IGF receptors. Addition of IGF-binding protein to PAEC previously incubated with IGF-I caused a marked dissociation of bound IGF-I (47% dissociation within 12h). These results indicate that the acid-stable IGF-binding protein which appears to be a part of the 150 kDa GH-dependent binding protein, blocks binding of IGF-I and -II by the IGF receptors and appears to exhibit a higher affinity for IGF-I than the endothelial type-I IGF receptor. The ramifications of this latter point with respect to transfer of circulating IGFs (bound to their IGF-binding proteins) across the vascular endothelium are not clear.

The effects of nuts on coronary heart disease risk.

Epidemiologic studies have consistently demonstrated beneficial effects of nut consumption on coronary heart disease (CHD) morbidity and mortality in different population groups. Clinical studies have reported total and low-density lipoprotein cholesterol-lowering effects of heart-healthy diets that contain various nuts or legume peanuts. It is evident that the favorable fatty acid profile of nuts (high in unsaturated fatty acids and low in saturated fatty acids) contributes to cholesterol lowering and, hence, CHD risk reduction. Dietary fiber and other bioactive constituents in nuts may confer additional cardioprotective effects.