Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of glucocorticoids on adipose tissue lipolysis in animals and humans is controversial. To determine whether a physiological increase in plasma cortisol, similar to that observed in diabetic ketoacidosis and other stress conditions, stimulates lipolysis, palmitate kinetics were measured in seven nondiabetic volunteers on two occasions with [1-14C]palmitate as a tracer. Subjects received a 6-h infusion of either 2 micrograms.kg-1.min-1 hydrocortisone or saline in random order. On both occasions, a pancreatic clamp (0.12 micrograms.kg-1.min-1 somatostatin, 0.05 mU.kg-1.min-1 insulin, and 3 ng.kg-1.min-1 growth hormone) was used to maintain plasma hormone concentrations at desired levels. Plasma cortisol concentrations increased to approximately 970 nM during cortisol infusion. Palmitate rate of appearance (Ra) and concentration increased by approximately 60% during cortisol infusion but did not change during saline infusion. Increments in palmitate Ra and concentration over the 6-h study were significantly greater during cortisol than saline infusion when compared by area-under-the-curve analysis (152 +/- 52 vs. -48 +/- 23 mumol.kg-1 and 12.2 +/- 4.1 vs. -4.9 +/- 4.1 mmol.min-1.L-1, respectively; P less than 0.02). Plasma glucose concentrations did not change significantly during cortisol (5.0 +/- 0.3 vs. 6.1 +/- 0.6 mM, NS) or saline (4.9 +/- 0.2 vs. 4.9 +/- 0.1 mM, NS) infusion. In nondiabetic volunteers, a 6-h cortisol infusion was associated with a 60% increase in palmitate Ra that did not occur with saline infusion. Thus, physiological hypercortisolemia may contribute to the increased rates of lipolysis observed in humans during stress.
Diabetes 1991 Oct
PMID:Stimulation of lipolysis in humans by physiological hypercortisolemia. 193 85

Controversy exists regarding whether plasma glucose concentrations are independently involved in the regulation of adipose tissue lipolysis. In the present study, six subjects with insulin-dependent diabetes and six nondiabetic volunteers were studied during infusion of somatostatin, growth hormone, and insulin at rates designed to maintain basal rates of lipolysis, which was traced using a constant infusion of [1-14C]palmitate. A euglycemic (approximately 5 mmol/l) clamp was performed for 3 h, followed by 3 h of hyperglycemia (approximately 9 and approximately 11 mmol/l in nondiabetic and diabetic subjects, respectively). Ten nondiabetic subjects were studied during 6 h of euglycemia to exclude time-dependent changes in lipolysis. The results showed that palmitate concentrations did not change between euglycemia and hyperglycemia in either group [118 +/- 10 vs. 132 +/- 14 mumol/l and 145 +/- 21 vs. 134 +/- 15 mumol/l in nondiabetic and diabetic subjects, respectively; both P = not significant (NS)]. Similarly, palmitate rate of appearance (Ra) did not change during hyperglycemia (1.0 +/- 0.1 and 1.7 +/- 0.4 mumol.kg-1.min-1 in nondiabetic and diabetic subjects, respectively) compared with euglycemia (1.0 +/- 0.1 and 1.6 +/- 0.4 mumol.kg-1.min-1 in nondiabetic and diabetic subjects, respectively; P = NS). Palmitate concentrations and Ra did not change during 6 h of euglycemia in nondiabetic volunteers. Thus hyperglycemia per se has no effect on free fatty acid turnover. Changes in lipolysis that occur coincident with hyperglycemia are probably due to changes in other circulating substrates or hormones known to affect lipolysis.
 ...
PMID:Lack of effect of hyperglycemia on lipolysis in humans. 197 22

To determine whether physiological changes in plasma glucagon concentrations are important in regulating basal adipose tissue lipolysis, FFA flux ([1-14C]palmitate) was measured in response to increases and decreases in plasma glucagon. Eight volunteers with insulin-dependent diabetes mellitus (IDDM) and nine healthy nondiabetic volunteers were studied using the pancreatic clamp technique to control plasma insulin, GH, and glucagon concentrations at desired levels. Palmitate flux at the chosen euglucagonemic hormone infusion rates was similar to baseline values (1.73 +/- 0.12 vs. 1.75 +/- 0.23 and 1.35 +/- 0.18 vs. 1.35 +/- 0.16 mumol/kg.min, respectively, in IDDM and nondiabetic subjects). No significant changes in palmitate flux occurred in response to glucagon withdrawal or mild (nondiabetic volunteers) or high physiological (IDDM volunteers) hyperglucagonemia. Thus, under conditions of normal FFA availability, changes in plasma glucagon concentrations within the physiological range have little or no effect on adipose tissue lipolysis.
 ...
PMID:Effects of glucagon on free fatty acid metabolism in humans. 199 2

The fatty acid composition of serum cholesterol esters was investigated in 325 subjects with normal glucose tolerance, 97 subjects with impaired glucose tolerance (IGT), and 98 subjects with non-insulin-dependent diabetes mellitus (NIDDM) identified by population-based screening. The proportions of palmitic acid (16:0) and palmitoleic acid (16:1) in serum cholesterol esters increased from the normal glucose tolerance group to the IGT and diabetic groups. On the other hand, the proportion of linoleic acid (18:2) was lower in diabetic subjects than in the subjects with IGT or normal glucose tolerance. The proportions of gamma-linolenic (18:3), dihomo-gamma-linoleic (20:3), and arachidonic (20:4) acids were highest in diabetic subjects and lowest in subjects with normal glucose tolerance. Our findings suggest that subjects with NIDDM or IGT have had higher dietary intake of saturated fatty acids. Both serum insulin and blood glucose concentrations probably have an effect on the elongation and desaturation of fatty acids, but the metabolism of linoleic acid to prostaglandin precursors seems to be different in different types of diabetes, NIDDM patients showing no abnormalities. The possibility that the fatty acid composition of plasma and membrane lipids has a role in insulin resistance and blood glucose regulation deserves further investigation.
 ...
PMID:Fatty acid composition of serum cholesterol esters in different degrees of glucose intolerance: a population-based study. 224 69

Binding equilibria of long-chain fatty acids to human serum albumin, in serum or plasma, were studied by a dialysis exchange rate technique. Palmitate was added to citrated plasma in vitro and it was observed that between six and ten palmitate molecules were bound to albumin with nearly equal affinity. Observations in vivo gave similar results in the following series: (a) in two volunteers with increased fatty acid concentrations after fasting, exercise, and a cold shower: (b) in three male volunteers in whom high concentrations of non-esterified fatty acids, up to 4.6 mM, were induced by intravenous administration of a preparation of lecithin/glycocholate mixed micelles, and (c) in 81 patients with diabetes mellitus, type I. The binding pattern of palmitate in serum or plasma is essentially different from that observed with palmitate added to buffered solutions of pure albumin when two molecules are tightly bound and about four additional molecules with lower affinity. The differences may partly be explained by the presence of chloride ions in blood plasma, reducing the affinity for binding of the first two fatty acid molecules, and partly by facilitated binding of several molecules of mixed fatty acids, as found in plasma.
 ...
PMID:Multiple fatty acid binding to albumin in human blood plasma. 233 79

In situ perfusion of the fetal side of the placenta of five normal and eight diabetic anaesthetized rabbits was performed. The does were infused with a mixture of 14C palmitic acid and 3H glucose whilst simultaneous maternal blood and placental perfusate samples were taken for 90 min. Radiolabelled palmitate and glucose levels in the perfusate closely followed levels in the maternal plasma in both normal and diabetic animals. Total placental non-esterified fatty acid transfer was 0.96 mumol/min in the diabetic animals, although due to the considerable variation within the groups this was not statistically significantly more than the 0.58 mumol/min transferred in the normal rabbits. This transfer was significantly affected by maternal uteroplacental blood flow. Total placental glucose transfer was significantly raised in the diabetic (5.0 mumols/min) compared with the normal (1.8 mumols/min) animals, reflecting maternal hyperglycaemia in the diabetic rabbits. Placental glucose transfer was also significantly correlated with maternal uteroplacental blood flow. Maternal diabetes thus increases the placental flux of nutrients to the fetus in the rabbit.
Diabetes Res 1989 Jun
PMID:The effect of alloxan induced diabetes in the rabbit on placental transfer of glucose and non-esterified fatty acids. 262 Apr 85

Previously, a small implant of compressed insulin in palmitic acid provided a basal dose to reduce hyperglycaemia for 42 +/- 12 d in rats with induced diabetes. This study describes a silicone implant that can be used for preprandial dose supplements. The device consists of two compartments assembled by attaching a 9 mm diameter foam ring to a 6 mm diameter ring of the same material. The assembly is then enclosed between two membranes, and an annular external wall. Before sealing, a 6 mg piece of compressed insulin (Zn) is inserted into the smaller ring with 2 mg tetracycline to hinder microbial growth. The top membrane is pierced once with an 18 gauge needle, and the device is tested by implanting under the abdominal skin of diabetic rats. Serous fluid soon enters to fill the 141 microliter internal volume through the orifice and dissolves some of the insulin which does not leak out. Sidewise compression weekly over the skin fold of the unanesthetized animal shows that the insulin remained potent until used up after 154 d. When compressed daily, the insulin supply lasted for 24 +/- 4 d and maintained the blood glucose consistently at 3.4 +/- 1.1 mM/l for 6-8 h each day. The dependable device is refillable percutaneously by injection of an insulin suspension.
 ...
PMID:Implantable reservoir for supplemental insulin delivery on demand by external compression. 265 24

Fatty acids in erythrocyte membranes and plasma were determined by capillary gas-liquid chromatography in 27 controls and 44 subjects with insulin-dependent diabetes mellitus. Significant decreases in stearic acid (P less than 0.00003) and arachidonic acid (P less than 0.001) and significant increases in palmitic acid (P less than 0.00003) were observed in erythrocytes from diabetic patients. The stearic:oleic acid ratios and arachidonic:linoleic acid ratios in erythrocytes were significantly lower in diabetic patients than in controls (P less than 0.0003 and less than 0.0007, respectively). The relative concentration of palmitic acid in plasma (as a percentage of the sum of the five major fatty acids) was increased in diabetic patients, as compared with controls (P less than 0.0125). We observed no other significant differences in fatty acids in plasma, making it unlikely that changes in fatty acids in erythrocyte membranes in diabetic patients can be accounted for simply by alterations in the fatty acids in plasma. We propose that impaired metabolic control associated with diabetes mellitus may interfere with the maintenance of fatty acid profiles in erythrocyte membranes against the concentration gradients in plasma.
 ...
PMID:An alternative explanation for the changes in erythrocyte fatty acids observed in diabetes mellitus. 311 55

An implant made of insulin in palmitic acid provides a basal dose sufficient to reduce hyperglycemia for 42 +/- 12 days in rats with induced diabetes. For preprandial dose supplements another arrangement is required. In this study a device consisting of a reservoir is assembled by attaching a 1 cm diameter foam ring to a 5 mm diameter piece of the same material. A 6 mg piece of compressed insulin is inserted into a cut between the ring and the attachment, along with 2 mg tetracycline to hinder microbial growth. The assembly is then enclosed between two membranes and an annular external wall. The top membrane is pierced once, and the device is tested by implantation under the abdominal skin of diabetic rats. Serous fluid will enter the interior through the orifice and leach the solid insulin that does not leak out. Daily sidewise compression over the skinfold of the unanesthetized animal indicated that the insulin supply lasted for 24 +/- 4 days. The blood glucose was consistently maintained at 3.4 +/- 1.1 mmol/L for 6-8 hr each day. After depletion the device can be refilled percutaneously by injecting insulin suspended in phosphate-buffered saline.
 ...
PMID:Supplemental insulin delivery from an implanted reservoir activated by external compression. 319 19

Myocardial fatty acid metabolism was studied in spontaneously-diabetic "BB" Wistar rats. The study involved 4 groups: control Wistar rats, nondiabetic littermates of "BB" Wistar rats, insulin-treated diabetic "BB" rats, and diabetic "BB" rats in which insulin treatment was removed 24 hours prior to study (uncontrolled diabetes). Hearts were perfused for 30 minutes as isolated working hearts in perfusate containing 1.2 mM (1-14C)-palmitate bound to 3% albumin, and 11 mM glucose. Palmitate oxidative rates, calculated as micromoles palmitate oxidized per gram dry weight per minute, were significantly decreased in both diabetic groups (0.447 +/- 0.043 and 0.528 +/- 0.038 in uncontrolled diabetic and treated diabetic versus 0.584 +/- 0.032 and 0.629 +/- 0.033 in nondiabetic littermate and control rats, respectively). This decrease was accompanied, however, by a significant decrease in the heart rate of these 2 groups when compared with control or nondiabetic animals. If the decreased heart function in the diabetic animals was accounted for, no decrease in palmitate oxidative rates occurred, suggesting that fatty acid oxidative metabolism is not impaired in the diabetic myocardium. In the uncontrolled diabetic rats, an increased rate of palmitate incorporation into myocardial triglycerides was seen compared with treated diabetic, nondiabetic littermates, and control rats (8.5 +/- 0.3 mumol/g dry wt/30 min versus 4.8 +/- 0.3, 5.9 +/- 0.7, and 5.7 +/- 0.3, respectively). Myocardial levels of coenzyme A were elevated in the uncontrolled diabetic rats compared with all other groups (647 +/- 25 nmol/g dry wt versus 484 +/- 27, 508 +/- 56, and 534 +/- 9, in treated diabetic, nondiabetic, and control rats, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Metabolism of palmitate in isolated working hearts from spontaneously diabetic "BB" Wistar rats. 331 91


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