Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, in vitro B-cell models are described, which may be applicable for studying the reported B-cell desensitization produced by hyperglycemia in IDDM and NIDDM. Using a programmable perifusion/perfusion system, insulin secretion from perifused islets was measured at 10-30-min intervals for 24-50 h. After 3-4 h continuous glucose (11 mM), a new phase of insulin release occurs in which secretion declines to, and remains at, approximately 25% maximal release. Results were similar when using: perifused islets embedded in Cytodex 3, or Bio-Gel P-2, 100-200 mesh; batchincubated islets with hourly changes of medium; and the isolated pancreas perfused for 8 h. Three different media, Hana HB 104 (fortified, fully defined medium), RPMI-1640 + 10% FBS, and perfusion bufferalbumin, were used. Despite reduced secretion to continuous glucose, each system responded vigorously to an acute stimulation with glucose-forskolin. Decreased secretion was primarily caused by decreased secretagogue efficiency (reduced fractional secretion). Prolonged stimulation with glucose or glucose-IBMX produced a similar waning of secretion regardless of the amount of insulin released. It is concluded that the third phase of insulin secretion may represent a secret-agogue-induced, signal desensitization of the B-cell, rather than exhaustion of a B-cell compartment of stored insulin.
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PMID:The third phase of in vitro insulin secretion. Evidence for glucose insensitivity. 351 47

Groups of young adult rats with body weights of 125-135 g (group A) or 300-400 g (group B) were subjected to one bout of prolonged exercise to exhaustion on a treadmill and were studied 2 h postexercise. Liver glycogen levels were markedly depleted in the exercised rats. Adipocytes from group A exercised rats showed a significantly greater increase in pyruvate dehydrogenase (PDH) activity in response to insulin than those from sedentary controls. Incubation with insulin of liver particulate fractions from exercised group A rats resulted in an increased production of a mitochondrial PDH activator compared with preparations from sedentary controls. The tissues of both exercised and sedentary group B rats were less responsive to insulin than those of the smaller rats. A significant effect of exercise on increased production of a PDH activator in response to insulin was found only in experiments in which adipocyte plasma membranes were coincubated with mitochondria and insulin. For group B rats exercise provided no significant enhancement of insulin activation of intact adipocyte PDH or stimulation of the production of a PDH activator by liver particulate preparations. Insulin binding to fat cells was not affected by exercise. Group A rats made insulin resistant by a high-fat diet did not respond to exercise by significantly increasing the insulin stimulation of PDH activator by liver membranes. The enhancing effect of a single bout of exercise on insulin response was not readily demonstrable in rats resistant to insulin either in association with age and weight or with a high-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of acute exercise on insulin generation of pyruvate dehydrogenase activator by rat liver and adipocyte plasma membranes. 352 20

Six men were studied during exercise to exhaustion on a cycle ergometer at 73% of VO2max following ingestion of glycerol, glucose or placebo. Five of the subjects exercised for longer on the glucose trial compared to the placebo trial (p less than 0.1; 108.8 vs 95.9 min). Exercise time to exhaustion on the glucose trial was longer (p less than 0.01) than on the glycerol trial (86.0 min). No difference in performance was found between the glycerol and placebo trials. The ingestion of glucose (lg X kg-1 body weight) 45 min before exercise produced a 50% rise in blood glucose and a 3-fold rise in plasma insulin at zero min of exercise. Total carbohydrate oxidation was increased by 26% compared to placebo and none of the subjects exhibited a fall in blood glucose below 4 mmol X 1-1 during the exercise. The ingestion of glycerol (lg X kg-1 body weight) 45 min before exercise produced a 340-fold increase in blood glycerol concentration at zero min of exercise, but did not affect resting blood glucose or plasma insulin levels; blood glucose levels were up to 14% higher (p less than 0.05) in the later stages of exercise and at exhaustion compared to the placebo or glucose trials. Both glycerol and glucose feedings lowered the magnitude of the rise in plasma FFA during exercise compared to placebo. Levels of blood lactate and alanine during exercise were not different on the 3 dietary treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the effects of pre-exercise feeding of glucose, glycerol and placebo on endurance and fuel homeostasis in man. 353 95

Plasma glucose, insulin, glucagon and growth hormone responses to both oral glucose and iv arginine were evaluated in 15 heroin addicts and 15 control subjects matched for age, sex and weight. The heroin users had an exaggerated rise in plasma glucose concentrations following oral sugar, which persisted until the end of the study (102 +/- 5 mg/dl in addicts vs 72 +/- 3 mg/dl in controls at 240 min, p less than 0.01) and significantly lower insulin responses (insulin peak 28 +/- 4 microU/ml in addicts vs 67 +/- 8 microU/ml in controls, p less than 0.01). The inhibitory effect of glucose on glucagon concentrations was less evident in addicts than in controls. The responses of plasma glucose, insulin and glucagon to arginine were not significantly different between addicts and controls, while the growth hormone rise was significantly greater in addicts. These results demonstrate that heroin users have impaired insulin secretion to oral glucose but not to arginine and suggest that: the impaired insulin secretion in heroin addicts is not dependent on beta-cell exhaustion, and a selective inhibition of glucose-induced insulin secretion is operative in these subjects, as it happens in patients with noninsulin-dependent diabetes mellitus.
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PMID:Impaired insulin response to glucose but not to arginine in heroin addicts. 354 79

Sulfonylureas seem to have similar mechanisms of action, including an acceleration and increase of insulin secretion, an increase of the systemic availability of insulin, and probably indirectly, an increase of insulin action. Sulfonylureas may postpone the development of impaired glucose tolerance (IGT) to manifest non-insulin-dependent diabetes mellitus (NIDDM), and all NIDDM subjects should benefit from sulfonylurea treatment except those in whom insulin secretion has been attenuated. The most effective use is the combination of diet restriction and sulfonylurea introduced in NIDDM subjects soon after transition from IGT to NIDDM. A simple screening procedure has been devised to find the subjects at this early stage. Newer sulfonylureas, such as glipizide and glyburide, are more potent than the older ones, such as tolbutamide and chlorpropamide. During chronic treatment, glipizide and glyburide seem to be equally effective in reducing blood glucose levels, and they do so without causing a chronic elevation of insulin secretion, signifying that they do not increase the risk of pancreatic B cell exhaustion. Glipizide has rapid and complete absorption, as well as a rapid distribution and elimination. This may explain why it is less liable than other sulfonylureas to provoke long-lasting hypoglycemia, which is the major danger when using sulfonylureas. Despite its rapid elimination, 7.5 to 15 mg glipizide can be administered once daily without loss of therapeutic efficacy. This may be due in part to enterohepatic recirculation of the drug in response to meals. The therapeutic efficacy is increased if glipizide is received half an hour before breakfast.
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PMID:Clinical pharmacology of sulfonylureas. 354 16

Six men were studied to compare the effects of pre-exercise carbohydrate feedings on endurance performance and muscle glycogen utilization during prolonged exercise. Trials consisted of a cycling ride to exhaustion at 75% maximal oxygen uptake preceded by the ingestion of either 75 g of glucose in 350 ml of water (GLU), 75 g of fructose in 350 ml of water (FRU), or 350 ml of an artificially sweetened and flavored placebo (CON). No differences were observed between trials for oxygen uptake, respiratory exchange ratio, heart rate, or exercise time to exhaustion (CON = 92.7 +/- 5.2 min, FRU = 90.6 +/- 12.4, and GLU = 92.8 +/- 11.3, mean +/- SE). Blood glucose was elevated as a result of the GLU feeding, but fell rapidly with the onset of exercise, reaching a low of 4.02 +/- 0.34 mmol X l-1 at 15 min of exercise. Serum insulin also increased following the GLU feeding but had returned to pre-drink levels by 30 min of exercise. No differences in blood glucose and insulin were observed between FRU and CON. Muscle glycogen utilization during the first 30 min of exercise (CON = 46.3 +/- 8.2 mmol X kg-1 wet weight, FRU = 56.3 +/- 3.0 mmol X kg-1 wet weight, GLU = 50.0 +/- 4.9 mmol X kg-1 wet weight) and total glycogen use (CON = 93.4 +/- 11.1, FRU = 118.8 +/- 10.9, and GLU = 99.5 +/- 4.3) were similar in the three trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of pre-exercise carbohydrate feedings on endurance cycling performance. 354 9

Nucleotide concentrations were measured in isolated pancreatic islets from rats using HPLC. This method was used to study the role of nucleotides in islets, which were perifused for several hours with different substrates and exhibited signs of exhaustion. Using islet tissue extracts, it was possible to determine 11 nucleotides. It was hoped that alterations in islet nucleotide concentrations would provide clues for the biochemical basis for the exhaustion phenomenon; however, changes in nucleotide concentrations that were observed in exhausted islet tissue did not correlate with corresponding changes in insulin release. Therefore, they are unlikely to be directly related to islet exhaustion.
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PMID:HPLC analysis of nucleotide profiles in glucose-stimulated perifused rat islets. 354 16

To determine the effects of food deprivation on the physical, physiological, and metabolic responses to exercise in the heat, adult, male rats (330-360g, N = 16/group) were food-deprived for 24, 48, or 72 h. They were then exercised (9.14m X min-1) in the heat (35.5 degrees C) to hyperthermic exhaustion (Tco approximately 43 degrees C). Food deprivation had no effects on endurance, but ad lib fed controls manifested significantly (p less than 0.05) increased Tco and Tsk during the latter portion of the treadmill interval. While plasma osmolality was significantly (p less than 0.01) increased in all groups as a result of the heat/exercise contingency, hematocrit ratios were elevated (p less than 0.01) as a result of 48 and 72 h of food deprivation. Food deprivation resulted in severe hypoglycemia following exercise (p less than 0.01), and these decrements were accompanied by marked (p less than 0.01) reductions in circulating insulin levels. Prolonged food deprivation (48 and 72 h) resulted in significant (p less than 0.01) hypertriglyceridemia and hyperlactacidemia subsequent to exercise. Levels of sodium, potassium, urea nitrogen, and creatine phosphokinase were unaffected by the food deprivation intervals. We have concluded from these studies that while several thermoregulatory and metabolic responses to exercise in the heat can be significantly affected by food deprivation, short-term endurance capacity was unaltered.
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PMID:Food deprivation and exercise in the heat: thermoregulatory and metabolic effects. 389 96

The effects of prior high-intensity cycle exercise (85% VO2 max) to muscular exhaustion on basal and insulin-stimulated glucose metabolism were studied in obese, insulin-resistant, and normal subjects. Six obese (30.4% fat) and six lean (14.5% fat) adult males underwent two separate, two-level hyperinsulinemic-euglycemic clamp studies (100-min infusions at 40 and 400 mU/m2/min), with and without exercise 12 h earlier. Carbohydrate oxidation was estimated by indirect calorimetry using a ventilated hood system, and endogenous glucose production by D-(3-3H)-glucose infusion. Glycogen content and glycogen synthase activity (GS %l) were measured in vastus lateralis muscle biopsies before and at the end of each insulin clamp procedure. After exercise, the obese and lean subjects had comparably low muscle glycogen concentrations (0.10 versus 0.08 mg/g protein, respectively), and equal activation of muscle GS activity (54.4 versus 45.3 GS %l, respectively). In the obese subjects, insulin-stimulated glucose disposal was increased significantly, but not totally corrected to normal. In both groups there was a comparable increase in nonoxidative glucose disposal (NOGD), whereas glucose oxidation was decreased and lipid oxidation was increased. Thus, the major effect of prior exercise was to increase insulin-stimulated glucose disposal in the obese subjects and to alter the pathways of glucose metabolism to favor NOGD and decrease glucose oxidation. No correlation was found between the exercise-induced increase in GS %l and NOGD, except in the normal subjects during maximal insulin stimulation. Thus, glycogen synthase activity does not appear to be rate-limiting for NOGD at physiologic insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men. 393 Mar 21

To determine the effects of dietary manipulation on the metabolic, physical, and physiological responses to exercise in the heat, adult male rats (n 5 16/group) were food deprived for 72 h followed by ad lib consumption of a high protein (HIPROT) or high carbohydrate (HICARB) diet for 96 h. Each dietary regimen was followed immediately by exercise (9.14 m . min-1) in the heat (35.58C) to hyperthermic exhaustion (TCO approximately 43 8C). Animals consuming the HICARB or HIPROT diet had an increased mean TCO prior to the acute heat/exercise protocol when compared with a control (CONT) group with uninterrupted access to a normal rodent diet; the HICARB rats also manifested a decreased endurance when compared with the CONT group. Plasma levels of urea nitrogen, lactate, and potassium were increased following exercise in the heat in all groups, but greatly exacerbated increments in urea nitrogen occurred in the HIPROT group. Following exercise, significant increments occurred in circulating levels of glucose and insulin in the HIPROT and HICARB groups. Plasma triglycerides were decreased by the exercise/heat regimen but increased by both diets. Thus, these dietary manipulations elicited a variety of metabolic responses which did not markedly alter the physiological and physical effects of work in the heat.
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PMID:Dietary manipulation and exercise in the heat: thermoregulatory and metabolic effects in rats. 394 68


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