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Biomedical subjects

C D Saudek

Publications and source records attributed to C D Saudek.

At least 55 records · Page 3Linked to original sources
PubMed1986

Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs.

Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin for 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the [6-3H]glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 microU/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. It is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production.

Animals↗
PubMed1985

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.

Animals↗
PubMed1984

Repeated hospitalization for diabetic ketoacidosis. The game of "Sartoris".

Repeated hospital admission is a serious problem for both the patient and the health care system. The life story of a patient repeatedly admitted for treatment of exacerbations of a chronic disease, such as diabetic ketoacidosis, can often be compared to Faulkner's family Sartoris. The Sartoris characters were wholly occupied in the pursuit of their painful decline and eventual demise. At the Johns Hopkins Hospital, 45 persons were identified who were repeatedly admitted to the medical service for diabetic ketoacidosis. Forty-two charts of "recidivist" patients and "non-recidivist" control patients matched for age and severity of disease were reviewed to determine factors that, if corrected, would prevent repeated admission. Case reports of three patients who were admitted an average of 11 times annually for several years are presented. Implications of the "Game of Sartoris" for the American teaching hospital are discussed.

Adult↗
PubMed1983

Hyperphagia alters cholesterol dynamics in diabetic rats.

Rats with streptozotocin-induced diabetes stop growing and start eating more chow. These two events elicit an interacting series of changes in cholesterol dynamics. Hyperphagia increases dietary cholesterol intake and cholesterol synthesis by the small intestine. These increases are balanced by a decrease in cholesterol synthesis in the rest of the body so that total cholesterol input is normal. With growth failure, utilization of cholesterol for formation of new tissue ceases. This decrease is balanced by an increase in bile acid synthesis by the liver. The bile acid pool in the contents of the small intestine is enlarged by hyperphagia. Despite these changes, fecal sterol excretion and total utilization of cholesterol are normal. During the course of changes in growth and food intake and the attendant changes in cholesterol flux, the total tissue cholesterol pool does not change. Therefore influx equals efflux and the systems regulating cholesterol and bile acid synthesis are responding appropriately and are themselves unperturbed by insulin deficiency. However, plasma cholesterol level increases threefold. This elevation is due to increased influx of cholesterol from the small intestine and decreased synthesis in the rest of the body, so that a larger portion of total body cholesterol influx passes through the blood.

Animals↗
PubMed1982

Preventing hyperphagia normalizes 3-hydroxy-3-methylglutaryl-CoA reductase activity in small intestine and liver of diabetic rats.

Rats with streptozotocin-induced diabetes stop growing, develop high cholesterol and triacylglycerol levels in plasma, and have decreased activity of the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (EC 1.1.1.34), in liver and increased activity in small intestine. They also eat more than normal. To determine the contribution of hyperphagia to these changes in lipid metabolism, we restricted intake of chow to the amount eaten ad lib by normal rats. Rats were meal-fed for 8 or 22 days from the time diabetes was induced. This regimen normalized reductase activity in both liver and intestine at mid-dark and mid-light, and all but eliminated high plasma cholesterol and triacylglycerol levels, although plasma insulin remained low and glucose remained high. Activation of hepatic reductase by endogenous phosphatase in vitro was reduced in hyperphagic diabetic rats but was normal in diabetic rats eating a normal amount of food. We conclude that hyperphagia, rather than direct effects of insulin deficiency as is usually assumed, is responsible for perturbations of lipid metabolism in chronically diabetic rats. These results support the proposal that hyperphagia increases the input of dietary and newly synthesized cholesterol from the small intestine, and that this increased input raises plasma cholesterol level and inhibits reductase activity in liver.

Animals↗
PubMed1982

Total hydroxymethylglutaryl CoA reductase activity in the small intestine and liver of insulin-deficient rats.

We examined the effect of streptozotocin-induced diabetes on the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (EC 1.1.1.34), in liver and small intestine of rats. During the acute phase of insulin deficiency (first day), food intake, plasma cholesterol, and reductase specific activity in liver all decreased. By 3 days, food intake, plasma cholesterol, and reductase activity in small intestine were all increasing. After 1 week, total reductase activity in small intestine was 2.5 times normal, whereas activity in liver remained low. Thus diabetes shifted the major site of cholesterol synthesis from the liver to the small intestine. These data support the proposal that hyperphagia by diabetic rats leads to increased input of both dietary and newly synthesized cholesterol by the small intestine into thoracic lymph and thereby contributes significantly to their hypercholesterolemia. The possibility that diabetes affected the F--inhibitable activation of reductase in vitro was also tested. There was no evidence of an effect in small intestine, but activation of reductase in vitro was decreased by 1/3 in liver. These data suggest that, in liver, either the activity of the activator was decreased or the fraction of reductase in the active state was increased after more than 12 hr of insulin deficiency.

Animals↗
PubMed1982

Hyperlipidemia - a diabetic emergency.

Treating hyperlipidemia in diabetics requires distinguishing between hypercholesterolemia, with its high risk of cardiovascular disease, and hypertriglyceridemia, which, if severe, may cause pancreatitis. Hypercholesterolemia is best managed with diet and, if necessary, colestipol and niacin. Hypertriglyceridemia with chylomicrons responds best to diabetic control, weight loss, and low-fat diet.

Adolescent↗
PubMed1982

Recovery and activation of hydroxymethylglutaryl coenzyme A reductase from rat small intestine.

We describe a method for estimating the total activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34) in the small intestine of rats. An homogenate of the whole small intestine is prepared rapidly and assayed directly to maximize the yield of enzyme and to minimize opportunity for uncontrolled change in activity. Fresh homogenate inhibits the expression of reductase in hepatic microsomes, has high HMG-CoA cleavage activity, and forms NADPH-independent metabolites which contaminate mevalonolactone isolated by thin-layer chromatography. When homogenate is preincubated, these interfering factors are decreased and reductase activity is increased. Part of this increase can be inhibited by F-. After freezing and preincubation, total reductase activity recovered from homogenates of small intestine from 300-g male rats at the middle of their dark period is 40 nmol mevalonate per min compared to 70 from hepatic microsomes. If F- is added at the time of homogenization, an activity of 11 nmol per min is recovered from each organ. Reductase in intestinal homogenate has an apparent Km for S-HMG-CoA of 4 microM.

Animals↗
PubMed1980

Feasibility of maintaining normal glucose profiles in insulin-dependent pregnant diabetic women.

This study was designed to test the feasibility of a patient-monitored glucose determination program to establish and maintain normal blood glucose levels. Ten pregnant women, who were insulin-dependent diabetics prior to becoming pregnant and who were in their eighth week or less of pregnancy, were offered the program. All 10 accepted and continued the program for the duration of their pregnancy. Normal plasma glucose (60 to 140; mean = 80 mg/dl) levels were achieved after one week of the program and were maintained throughout the pregnancy as documented by 5 to 8 blood glucose determinations a day. The hemoglobin A1c level, which was elevated in all 10 patients at the start (9.4 +/- 1.6 per cent) of the program, fell into the normal range (2 to 5.0 per cent) five weeks after glucose values became normal. Serum estradiol (0.8 +/- 0.6 ng/ml), serum prolactin (10 +/- 9 ng/ml) and serum human chorionic gonadotropin (5,500 +/- 1,700 ng/ml), although all abnormal at the start of the program, became normal after glucose control was achieved (program weeks 4, 5 and 6, respectively). The infants showed no signs of macrosomnia (2,988 +/- 959 g), hypoglycemia, hyperbilirubinemia, hypocalcemia, erythremia or respiratory distress. Therefore, a program to maintain normal blood glucose levels during a diabetic patient's pregnancy is not only possible but may also improve the pregnancy and the outcome.

Adult↗
PubMed1979

Human intestinal lipoproteins. Studies in chyluric subjects.

To explore the role of the human intestine as a source of apolipoproteins, we have studied intestinal lipoproteins and apoprotein secretion in two subjects with chyluria (mesenteric lymphatic-urinary fistulae). After oral corn oil, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) output in urine increased in parallel to urinary triglyceride. One subject, on two occasions, after 40 g of corn oil, excreted 8.4 and 8.6 g of triglyceride together with 196 and 199 mg apoA-I and on one occasion, 56 mg apoA-II. The other subject, after 40 g corn oil, excreted 0.3 g triglyceride and 17.5 mg apoA-I, and, after 100 g of corn oil, excreted 44.8 mg apoA-I and 5.8 mg apoA-II. 14.5+/-2.1% of apoA-I and 17.7+/-4.3% of apoA-II in chylous urine was in the d < 1.006 fraction (chylomicrons and very low density lipoprotein). Calculations based on the amount of apoA-I and apoA-II excreted on triglyceride-rich lipoproteins revealed that for these lipid loads, intestinal secretion could account for 50 and 33% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Similarly, subject 2 excreted 48-70% and 14% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Chylous urine contained chylomicrons, very low density lipoproteins and high density lipoproteins, all of which contained apoA-I. Chylomicrons and very low density lipoproteins contained a previously unreported human apoprotein of 46,000 mol wt. We have called this apoprotein apoA-IV because of the similarity of its molecular weight and amino acid composition to rat apoA-IV. In sodium dodecyl sulfate gels, chylomicron apoproteins consisted of apoB 3.4+/-0.7%, apoA-IV 10.0+/-3.3%, apoE 4.4+/-0.3%, apoA-I 15.0+/-1.8%, and apoC and apoA-II 43.3+/-11.3%. Very low density lipoprotein contained more apoB and apoA-IV and less apoC than chylomicrons. Ouchterlony immunodiffusion of chylomicron apoproteins revealed the presence of apoC-I, apoC-II, and apoC-III. In contrast, plasma chylomicrons isolated during a nonchyluric phase revealed a markedly altered chylomicron apoprotein pattern when compared with urinary chylomicrons. The major apoproteins in plasma chylomicrons were apoB, apoE, and the C peptides: no apoA-I or apoA-IV were present in sodium dodecyl sulfate gels indicating that major changes in chylomicron apoproteins occur during chylomicron metabolism. When incubated in vitro with plasma, urinary chylomicrons lost apoA-I and apoA-IV and gained apoE and apoC. Loss of apoA-I and apoA-IV was dependent upon the concentration of high density lipoproteins in the incubation mixture. These studies demonstrate that the human intestine secretes significant amounts of apoA-I and apoA-II during lipid absorption. Subsequent transfer of apoproteins from triglyceride-rich lipoproteins to other plasma lipoproteins may represent a mechanism whereby the intestine contributes to plasma apoprotein levels.

Adult↗
PubMed1979

Cholesterol metabolism in diabetes: the effect of insulin on the kinetics of plasma squalene.

The turnover of isotopically labeled squalene formed in plasma from [14C]mevalonate has been used to measure cholesterol synthesis in diabetics over a 7-h period. Five patients were studied while in poor diabetic control (mean daytime glycemia, 349 mg/dl) and at a later date once improved control was established by multiple daily insulin injections (mean glycemia, 175 mg/dl). This degree of diabetic control resulted in an increase in the fractional conversion of [14C]mevalonic acid to [14C]squalene from 55.2 +/- 1% to 67.5 +/- 4% (P less than 0.025). These data together with the area under the squalene specific activity curve yeild an estimated rate of cholesterol synthesis based on the likely assumption that mevalonate pool size did not decrease. Insulinization increased this calculated mean rate of cholesterol synthesis from 961 +/- 151 to 1206 +/- 223 mg/day (P less than 0.025). The use of squalene kinetics to evaluate changes in cholesterol synthesis deserves further study, particularly in metabolically unstable states such as diabetes in which conventional methods for measuring cholesterol synthesis are difficult to apply and to interpret.

Adult↗
PubMed1978

Cholesterol metabolism in diabetes. I. The effect of diabetic control on sterol balance.

To evaluate the effect of diabetic control on sterol balance, five subjects (one with fasting chylomicronemia) were studied when they had little control of blood glucose (period I) and, continuously, when increased insulin dosage improved diabetic control (period II). The four subjects with no chylomicronemia showed a diminished fecal bile acid (FBA) excretion. Although fecal neutral steroid excretion increased variably, the total steroid balance was unchanged. The results support the concept that good control of diabetes shifts the fecal steroid excretion towards diminished FBA, but steroid balance methods did not reveal an effect of insulin on total steroid balance.

Adult↗