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K R Feingold

Publications and source records attributed to K R Feingold.

287 records · Page 16Linked to original sources
PubMed1982

The effect of diabetes on mevalonate metabolism in the rat.

Previous studies have demonstrated a major difference in mevalonate metabolism by male and female rats by both the shunt and sterol pathways. This important sex difference was shown to be related to the presence of oestrogens and/or progesterone. In the present study we have investigated the effects of streptozotocin-induced diabetes on mevalonate metabolism. Firstly, insulin deficiency decreased the ability of the rats to oxidize mevalonate to carbon dioxide by the shunt pathway both in vivo and in vitro. This decrease was reversed by insulin treatment both in the intact animals as well as in tissue slices. Secondly, diabetes caused a marked increase in hepatic sterologenesis in the intact animal. This is the first demonstration that insulin plays significant regulatory role in both the shunt and sterol pathways of mevalonate metabolism.

Animals↗
PubMed1982

The effect of diabetes mellitus on sterol synthesis in the intact rat.

Diabetes mellitus in both humans and animals is characterized by elevations in plasma cholesterol concentrations. The cause of this hypercholesterolemia is unknown. The present study employed tritiated water to quantity sterol synthesis in intact diabetic and control animals. Sterologenesis was 60-246% greater in the gut of diabetic animals than in controls. This enhancement of sterol synthesis occurred soon after the onset of diabetes and persisted for at least 3 wk. Moreover, insulin therapy markedly decreased gut sterol synthesis in diabetic animals to levels only slightly greater than in controls. Diabetes increased sterol synthesis primarily in the small intestine, but a small increase was also observed in the large intestine. Subfractionation of the small intestine into epithelial cell and muscularis cell layers revealed an increased sterologenesis in both layers. Quantitatively, though, the epithelial layer accounted for the majority of the enhancement of small intestine sterol synthesis observed in diabetic animals. De novo sterologenesis in tissues other than the intestines (liver, skin, stomach, or remaining carcass) was not significantly altered by diabetes. This study demonstrates that diabetes markedly stimulates sterol synthesis, an effect that is specifically localized to the intestines.

Animals↗
PubMed1982

De novo sterologenesis in intact primates.

Recent studies have demonstrated that in intact rodents, extrahepatic tissues are much more important sites of de novo sterologenesis than previously appreciated. The present investigation was undertaken to localize the sites of cholesterol and nonsaponifiable lipid synthesis in intact primates. Tritiated water was employed as the radiolabeled tracer for quantifying sterol synthesis. Our results indicate that in the intact primate, tissues other than the liver account for the majority of the newly synthesized cholesterol (74.5% to 84.4%) and nonsaponifiable lipids (77.3% of 86.5%). This extrahepatic sterologenesis is primarily localized to the intestine, skin, and carcass (all tissues not specifically analyzed). Sterologenesis in the other tissues made only a minor contribution to total animal cholesterol and nonsaponifiable lipid synthesis. Moreover, cholesterol feeding that inhibited hepatic and small intestinal sterol synthesis did not greatly affect skin or carcass sterologenesis. This indicates that transport of sterols from either the live or intestine to peripheral tissues does not contribute greatly to the newly synthesized sterols localized in extrahepatic, extraintestinal sites.

Animals↗
PubMed1981

The effect of decreased plasma cholesterol concentration on circulatinga mevalonate metabolism in rats.

Circulating mevalonate is metabolized by two mechanisms: the sterol pathways leading to cholesterol and the shunt pathway resulting in CO2 production. The kidney is the chief site of circulating mevalonate metabolism by both pathways. The present study investigated the effect of plasma cholesterol concentration on circulating mevalonate metabolism. 3-Aminopyrazolo(3,4-d)pyrimidine and Triton WR 1339 were utilized to induce "functional hypocholesterolemia". An enhancement of both renal total nonsaponifiable lipid synthesis (36-43%) and cholesterol synthesis (42%) from circulatinga mevalonate was observed when "functional hypocholesterolemia" was induced by either compound. Hepatic total nonsaponifiable lipid synthesis from circulating mevalonate was not enhanced in the Triton-treated animals, but 4-aminopyrazolo(3,4-d)pyrimidine treatment increased accumulation of total labeled nonsaponifiable lipids and cholesterol. No increase in labeled total nonsaponifiable lipids or cholesterol in the carcass was observed after treatment with wither compound. "Functional hypocholesterolemia" reduced the shunt pathway of circulating mevalonate metabolism by approximately 30%. This reduction occurred in both the renal and extrarenal shunt pathways. These data indicate that plasma cholesterol concentration regulates the in vivo metabolism of circulating mevalonate in that hypocholesterolemia reduces the shunt pathway and stimulates sterologenesis, and effect chiefly localized to athe kidneys.

Adenine↗
PubMed1980

Sex difference in human mevalonate metabolism.

Two pathways of mevalonate metabolism have been demonstrated: the major (sterol) pathway leads to cholesterol synthesis, whereas the second shunts mevalonate away from sterol production and ultimately results in its oxidation to CO2. Previous studies have demonstrated that the female rat metabolizes circulating mevalonate by the shunt pathway at twice the rate of the male, whereas the male rat converts significantly more circulating mevalonate to cholesterol than the female. The present study extends these observations to humans. Six men and five premenopausal women with normal renal function were injected with R,S-[5-14C]mevalonate, and 14CO2 expired in the breath of the subjects was monitored continuously with an ionization chamber. On an average, the female subjects expired 16.5% and the males 9.8% of the injected R-[5-14C]mevalonate (P less than 0.001). No differences were observed in the plasma and erythrocyte [14C]cholesterol levels. These data demonstrate, in human beings, a sex difference in mevalonate metabolism. The overall impact of the greater mevalonate shunt activity on cholesterol balance in women is unknown.

Adult↗
PubMed1980

Influence of thyroid hormone status on mevalonate metabolism in rats.

Mevalonate, an essential intermediate in cholesterol synthesis, is metabolized either to cholesterol or, by the shunt pathway, to CO2. Previous investigations have demonstrated that the kidneys are the chief site of circulating mevalonate metabolism and that sex hormones as well as insulin markedly influence circulating mevalonate metabolism. The present study examined in rats the influence of thyroid hormone status on mevalonate metabolism in vivo and in vitro. L-thyroxine administration increased renal conversion of circulating mevalonate to cholesterol, 41% in the females and 22% in the males. Conversely, hypothyroidism induced by 6 N propyl-2-thiouracil reduced renal conversion of circulatng mevalonate to cholesterol by 45% in females and 27% in males; thyroid hormone replacement in these animals returned cholesterogenesis in the kidneys to supranormal levels. Neither L-thyroxine nor hypothyroidism altered circulating mevalonate conversion to cholesterol in the liver or carcass. In vitro studies confirmed the in vivo observations. Changes in thyroid hormone produced only minor changes in the shunt pathway of mevalonate metabolism. This study demonstrates that the major effect of the thyroid hormone on the metabolism of circulating mevalonate is to alter the conversion of mevalonate to cholesterol, an effect localized solely to the kidneys.

Animals↗
PubMed1979

Acromegaly with normal growth-hormone levels and pituitary histology. Case report.

In rare cases, acromegalic patients have normal basal concentrations of growth hormone, and their acromegaly results from abnormal growth-hormone secretory patterns. A patient is reported with the clinical features of acromegaly, who had elevated somatomedin levels and an enlarged sella turcica, but whose serum growth-hormone levels on continuous monitoring were in the normal range, with levels of 2.8 to 8.9 ng/ml. Dynamic studies of growth hormone revealed normal responses to hypo- and hyperglycemia, but abnormal responses to L-dopa and thyroid-releasing hormone. At surgery, neither a pituitary adenoma nor eosinophilic hyperplasia was present. It is likely that this patient's acromegaly resulted from the presence of chronically high normal levels of growth hormone.

Acromegaly↗
PubMedDate not supplied

Testosterone regulates metabolism of plasma chylomicrons in rats.

Previously we demonstrated a marked sex difference in the metabolism of chylomicrons in adult rats. In males, radiolabeled chylomicrons displayed a longer dwell time on endothelial surfaces, which resulted in a decreased chylomicron uptake by the liver. The increased rate of chylomicron metabolism in females was associated with increased postheparin lipoprotein lipase activity. In the present study, we have investigated the effects of physiological doses of sex steroid hormones on the metabolism of chylomicrons and postheparin lipoprotein lipase activity. No sex differences were found in prepubertal animals. We also found no difference in chylomicron metabolism in control female, castrated female, estrogen-treated female, castrated male, and estrogen-treated male rats. However, control male, testosterone-treated male, and testosterone-treated female rats showed increased endothelial binding of chylomicrons and decreased chylomicron uptake by the liver. Postheparin lipoprotein lipase activity also was decreased by testosterone administration. In parallel with the alterations in chylomicron metabolism, serum high density lipoprotein levels in male rats decreased with testosterone administration. These results indicate that the differences in chylomicron metabolism, postheparin lipoprotein lipase activities, and serum high density lipoprotein levels observed between male and female rats are due to testosterone.

Animals↗
PubMedDate not supplied

Effect of interleukin-1 on lipid metabolism in the rat. Similarities to and differences from tumor necrosis factor.

Infection and inflammation are associated with hypertriglyceridemia, which is thought to be mediated by cytokines. Previous studies at our laboratory and others have shown that tumor necrosis factor acutely increases serum triglyceride levels primarily by stimulating hepatic lipid synthesis and secretion. The role of interleukin-1 (IL-1), a cytokine that is also secreted by stimulated macrophages and that has many actions that overlap those of tumor necrosis factor, has not been studied in depth. The present study demonstrates that IL-1, at doses similar to those that cause fever and anorexia and that stimulate adrenocorticotropic hormone secretion, rapidly increases serum triglyceride levels; this elevation persists for at least 17 hours. Serum cholesterol levels are not altered by IL-1. Neither is the clearance of triglyceride-rich lipoproteins affected by IL-1. However, hepatic triglyceride secretion, measured by the Triton WR-1339 technique, is increased in IL-1-treated animals. Accompanying this stimulation in hepatic lipid secretion is an increase in de novo fatty acid synthesis in the liver. IL-1 does not increase serum free fatty acid and glycerol levels, suggesting that IL-1 does not stimulate lipolysis in vivo. Additionally, inhibition of lipolysis does not prevent the increase in serum triglyceride levels, providing further evidence that lipolysis does not play a crucial role in the increased hepatic lipid synthesis and secretion induced by IL-1. In contrast, tumor necrosis factor increases lipolysis, which contributes to the increase in serum triglycerides. That multiple cytokines rapidly elevate plasma triglyceride levels suggest that these changes in lipid metabolism may play an important role in the organism's response to infection and inflammation.

Animals↗
PubMedDate not supplied

Relationship of muscle capillary basement membrane thickness and diabetic retinopathy.

We examined the relationship between the thickness of the quadriceps muscle capillary basement membrane and diabetic retinopathy. Basement membrane thickness was measured in two groups of patients with long-standing type II diabetes mellitus. One group of patients (N = 13) had no evidence of diabetic retinopathy on fluorescein angiography, whereas the other (N = 12) had proliferative microvascular disease. All the patients were male, and both groups were of similar ages, duration of diabetes, serum creatinines, and glycemic control as reflected by HbA1 levels. Mean muscle capillary basement membrane width (+/- SE) of the patients with proliferative retinopathy (3346 +/- 262) was significantly greater (P less than .05) than that observed in the patients without retinopathy (2660 +/- 177). The results of this study suggest that there is a relationship between capillary basement membrane thickness in skeletal muscle and the severity of microangiopathy in the eye. However, there was a substantial overlap between the two groups, indicating that for any individual patient the measurement of muscle capillary basement width will probably not be useful in identifying the presence or absence of retinopathy.

Aged↗
PubMedDate not supplied

Normalization of fasting blood glucose levels in insulin-requiring diabetes: the role of ethanol abstention.

The long-term remission of insulin-dependent diabetes mellitus is an unusual occurrence. The present report describes three cases of typical insulin-dependent diabetes in which the metabolic abnormalities greatly improved after the patients abstained from excessive ethanol intake. Our patients presented with polyuria, polydipsea, and weight loss of several weeks duration and laboratory studies revealed marked elevations in blood glucose concentrations and, in two of the three patients, mild ketosis. When these patients subsequently abstained from excessive ethanol intake, the elevations in blood glucose levels and the clinical symptoms of diabetes resolved. Two of our three patients have a strong family history of diabetes mellitus and we have therefore hypothesized that excessive ethanol intake only results in hyperglycemia in individuals with either an underlying predisposition to develop diabetes or mild unrecognized preexisting diabetes. It is important that clinicians recognize that excessive ethanol intake can lead to hyperglycemia and that abstention from ethanol may result in the marked improvement of the metabolic abnormalities.

Adult↗