Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ketone bodies are derived from the accelerated beta-oxidation of fatty acids during prolonged starvation or severely impaired carbohydrate metabolism. D-3-hydroxybutyrate (3OHB) is the major ketone circulating in the blood. Fully automated assay of 3OHB using a centrifugal analyzer was developed. The within-run and between-run levels of precision were acceptable, with coefficients of variation of from 0.75% to 4.35%. The recovery was 101.00 +/- 3.71%. The linearity was up to 5 mmol/L. Delayed serum separation even after 24 hours had no effect. The stability of 3OHB at -20 degrees C was greater than that at 4 degrees C when the serum was stored. No significant interference was observed with hemoglobin, bilirubin or triacylglycerol. NaF-treated plasma gave a significant underestimation of 3OHB. There was no significant difference in blood 3OHB between normal (blood glucose < or = 110 mg/dL, n = 87) and hyperglycemic subjects (blood glucose 110-200 mg/dL, n = 42), but when the blood glucose concentration was greater than 200 mg/dL, the difference in blood 3OHB between normal subjects and hyperglycemic patients became significant. The blood 3OHB concentrations increased according to the degree of hyperglycemia. There were sensitive changes in blood 3OHB during the treatment of a patient with diabetic ketoacidosis. The monitoring of blood 3OHB can be used clinically as an index of ketosis and as a signal of metabolic control in diabetes.
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PMID:Fully automated assay of blood D-3-hydroxybutyrate for ketosis. 810 81

The effect of insulinopenic diabetes on the expression of glucose transporters in the small intestine was investigated. Enterocytes were sequentially isolated from jejunum and ileum of normal fed rats, streptozotocin-diabetic rats, and diabetic rats treated with insulin. Facilitative glucose transporter (GLUT) 2, GLUT5, and sodium-dependent glucose transporter 1 protein content was increased from 1.5- to 6-fold in enterocytes isolated from diabetic animals in both jejunum and ileum. Insulin was able to reverse the increase in transporter protein expression seen after induction of diabetes. There was a four- to eightfold increase in the amount of enterocyte glucose transporter mRNA after diabetes with greater changes in sodium-dependent glucose transporter 1 and GLUT2 than in GLUT5 levels. In situ hybridization showed that after the induction of diabetes there was new hybridization in lower villus and crypt enterocytes that was reversed by insulin treatment. Thus, the increase in total hexose transport caused by diabetes is due to a premature expression of hexose transporters by enterocytes along the crypt-villus axis, causing a cumulative increase in enterocyte transporter protein during maturation. These changes are likely to represent an adaptive response by the organism to increase nutrient absorption in a perceived state of tissue starvation. These adaptive changes may lead to exacerbation of hyperglycemia in uncontrolled diabetes.
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PMID:Small intestine hexose transport in experimental diabetes. Increased transporter mRNA and protein expression in enterocytes. 811 95

The GLUT4 glucose transporter and type II hexokinase are predominantly expressed in skeletal muscle and adipose tissue. The effects of insulin and glucose on the expression of GLUT4 and HKII were studied in vivo by using the euglycemic-hyperinsulinemic and hyperglycemic-hyperinsulinemic clamp methods. The clamps were maintained in conscious rats for 6 or 24 h after a 1-day starvation period. Adipose tissue GLUT4 mRNA was increased 4-fold after 6 h and 23-fold after 24 h of hyperinsulinemia; HKII mRNA was increased by four- and eightfold after 6 and 24 h, respectively. In contrast, GLUT4 mRNA was not significantly changed in skeletal muscle by either the euglycemic- or hyperglycemic-hyperinsulinemic clamps. Each of these treatments resulted in a fourfold induction of HKII mRNA. No changes of GLUT4 protein and hexokinase activity were detected after 6 h of hyperinsulinemia in either skeletal muscle or adipose tissue. After 24 h of hyperinsulinemia, adipose tissue GLUT4 protein had doubled, whereas skeletal muscle GLUT4 was unchanged. In contrast, hexokinase activity increased by two- to eightfold in skeletal muscle and adipose tissue. Hyperinsulinemia alone was sufficient to mediate the effects observed, because no additional effects were seen when hyperglycemia accompanied hyperinsulinemia. These results reveal the lack of coordinate regulation of GLUT4 and HKII in adipose tissue and skeletal muscle. Whereas hyperinsulinemia increases both GLUT4 and HKII mRNA and protein levels in adipose tissue, this treatment increases HKII mRNA and protein in skeletal muscle, but has no effect on GLUT4 in this tissue.
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PMID:The effects of hyperinsulinemia and hyperglycemia on GLUT4 and hexokinase II mRNA and protein in rat skeletal muscle and adipose tissue. 849 14

Calcium influx through L-type voltage-dependent calcium channels (VDCCs) triggers insulin secretion. Until recently, the structure of VDCCs in pancreatic beta-cells and their regulation in altered metabolic states were not known. Study of the VDCC protein in skeletal muscle has shown that the alpha 1 subunit is functionally the most important subunit among the five subunits (alpha 1, alpha 2, beta, gamma and delta), acting as a voltage sensor and an ion-conducting pore. Molecular cloning of a novel alpha 1 subunit (beta-cell/neuroendocrine type, CACN4) of VDCCs from pancreatic islets and insulinoma have made it possible to study the electrophysiological and pharmacogical properties, regulation, and genetics of the VDCCs expressed in beta-cells. The CACN4 is structurally related to other members of the VDCC alpha 1 subunit family, including skeletal muscle, cardiac, and brain types. In situ hybridization experiments reveal that CACN4 mRNAs are expressed in beta-cells in the islets. Heterologous expression studies show that CACN4 in the presence of the beta subunit elicits L-type VDCC currents, although expression of CACN4 alone is not sufficient for VDCC activity. Studies of animal models with chronic hyperglycemia and starvation have indicated that the reduced CACN4 mRNA levels in pancreatic islets are associated with impaired insulin responses to stimuli in both hyperglycemic and fasting states. These studies demonstrate that CACN4 is the major component of VDCCs in pancreatic beta-cells and suggest that it plays a crucial role in the regulation of insulin secretion in normal and altered metabolic states.
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PMID:CACN4, the major alpha 1 subunit isoform of voltage-dependent calcium channels in pancreatic beta-cells: a minireview of current progress. 852 24

"Septic autocannabalism" been coined to describe the metabolic response that follows severe sepsis in humans. The normal protein- and energy-conserving mechanisms evoked during simple starvation are not observed following the onset of sepsis. The metabolic response to sepsis entails rapid breakdown of the body's reserves of protein, carbohydrate, and fat. Hyperglycemia with insulin resistance, profound negative nitrogen balance, and diversion of protein from skeletal muscle to splanchnic tissues are prominent features. These responses are believed to be mediated in large part by inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), and IL-6. Secondary induction of catecholamines, cortisol, and glucagon by cytokines is likely to be another important effector mechanism. Infection and inflammation elicit a complex network of interwoven responses, and no single mediator alone accounts for the responses observed. Sepsis also commonly involves alterations in cardiovascular function with altered flow to key metabolic sites, hypoxia, damage to the gut's mucosal barrier, secondary organ failure, and alterations in capillary permeability. These structural and functional alterations also strongly influence the metabolic profile during infection. If these catabolic responses persist for more than a few days, severe malnutrition results and is likely to be an important risk factor for mortality in these patients. The altered metabolic milieu during sepsis prevents effective use of exogeneously delivered glucose and protein; at best, administration of these agents ameliorates but does not prevent the persistence of catabolism. Delivery of agents that antagonize cytokines and other moieties such as glutamine and growth hormone may, in the future, help to restore nitrogen balance during sepsis.
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PMID:Metabolism of sepsis and multiple organ failure. 866 35

The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; anaesthesia was induced with propofol and maintained with propofol, fentanyl and N2O; muscle paralysis was obtained with atracurium. A small glottis was observed at laryngoscopy so that a 6 mm cuffed tube was inserted. Surgery lasted 75 minutes; the patient recovered promptly a few minutes following the end of propofol infusion; no postoperative complication was recorded. As hypoglycemia can occur during and after surgery in the Prader-Willi syndrome, plasma samples for glucose, NEFA, insulin, cortisol, and growth hormone (GH) were collected prior to the induction of anaesthesia (A), 20 minutes after starting surgery (B), at the end of surgery (C), and 3 hours later (D). In spite of the infusion of glucose, hyperglycemia was observed just in C and D samples (A:77; B:88; C:245; D:279 mg/dl). Stable NEFA values, within the normal range, were observed (A:77; B:88; C:245; D:279 mg/dl) suggesting poor or absent lipolysis. Insulin decreased progressively during surgery (A:10.5; B:8.8; C:5.4; D:7.0 mU/L). Cortisol peaked in B (A:9.5; B:20.9; C:13.4; D:4.8 micrograms/dl), suggesting normal hypothalamic reactivity to the surgical stimulus. Finally very low GH levels were observed (A:0.04; B:0.07; C:0.06; D:0.09 ng/ml) suggesting GH deficiency, which had possibly affected the size of patient's glottis. Our data support the hypothesis that hypoglycemia in the Prader-Willi syndrome originates from inadequate lipolysis during starvation.
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PMID:[General anesthesia in Prader-Willi syndrome]. 910 80

The development of malnutrition is often rapid in critically ill patients with sepsis and severe trauma. In such patients, a wide array of hormonal and nonhormonal mediators are released, inducing complex metabolic changes. Hypermetabolism, associated with protein and fat catabolism, negative nitrogen balance, hyperglycemia, and resistance to insulin, constitute the hallmark of this response. Critically ill patients demonstrate a marked alteration in the adaptation to prolonged starvation: resting metabolic rate and tissue catabolism stay elevated, while ketogenesis remains suppressed. The response to nutrition support is impaired. Substrate use is modified in septic and traumatized patients. Glucose administration during severe aggression does not suppress the enhanced hepatic glucose production and the lipolysis. This phenomenon, related to tissue insulin resistance, ensures a high flow of glucose to the predominantly glucose-consuming cells, such as the wound, the inflammatory, and immune cells, all insulin-independent cells. In addition, the elevated protein catabolism is difficult to abolish, even during aggressive nutrition support. Thus, in patients with prolonged aggression, these alterations produce a progressive loss of body cell mass and foster the development of malnutrition and it dire complications. In this review, the relevant physiologic data and the nutritional implications related to energy metabolism in septic and injured patients are discussed, while potential therapeutic strategies are proposed.
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PMID:Energy metabolism in sepsis and injury. 929 Jan 9

Chicken is characterized by a relative insulin resistance and a physiological hyperglycemia (2g/L) and is also subjected to fattening. Fat deposits in chicken, as in mammals, are regulated by environmental and genetic factors. In mammals, leptin, an adipose cell-specific secreted protein has been characterized that is encoded by ob gene. Leptin regulates satiety through hypothalamic specific receptors, energy balance, energy efficiency and contributes to adaptation to starvation. The leptin gene has been characterized in various mammalian species, and the cloning and sequencing of the chicken leptin gene (ob gene) are reported. Using RT-PCR and primers flanking the coding region of the leptin gene selected from known mammalian sequences, we have successfully amplified a 600-bp fragment from chicken liver and adipose tissue total ARNs. The amplified fragment exhibits a similar size to that of the coding region of the mammalian leptin gene. The sequences of the coding region of chicken liver and adipose tissue are identical and presented 97%, 96% and 83% similarity to the mouse, rat and human sequences, respectively. Finally, this is the first report showing that leptin gene expression in chicken is not exclusively localized in adipose tissue but is also expressed in liver. The expression of leptin in liver may be associated with a key role of this organ in avian species in controlling lipogenesis.
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PMID:Cloning the chicken leptin gene. 952 75

Acute illness induces major physiological responses, which favor the adaptation of the organism to stress and injury. The metabolic response plays key roles in maintenance of vital functions and promotion of the healing mechanisms. All the components of energy expenditure are modified, particularly the resting metabolism. The regulation of carbohydrate metabolism is also markedly altered. Such patients are characterized by fasting and postprandial hyperglycemia, insulin resistance, and by a stimulation of the hepatic glucose production in fasted and fed states. Lipolysis and increased fat oxidation are typically observed. Ketogenesis processes are inhibited, concurring to alter the adaptation to starvation. Protein turnover is stimulated with a preponderance of the catabolic processes, even during full nutritional support. This induces a state of resistance to feeding, leading to a progressive depletion of the fat free mass. Such progressive tissue catabolism cannot be reversed by hypercaloric nutrition or growth factors. Specific nutrients (aminoacids, micronutrients, PUFA) may offer interesting perspectives in stimulating immunity, improving the antioxidant balance or modulating the inflammatory response.
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PMID:[Nutrition and stress]. 1113 59

A weakness of many animal models of diabetes mellitus is the failure to use insulin therapy, which typically results in severe body wasting. Data collected from such studies must be interpreted cautiously to separate the effects of hyperglycemia from those of starvation. We provide several algorithms that were used by us in two long-term (20-week) experiments in which hyperglycemia (300 to 400 mg/dl), dyslipidemia (cholesterol [280 to 405 mg/dl] and triglycerides [55 to 106 mg/dl] concentrations), and positive energy balance were maintained in swine. Yucatan miniature swine groups included control, alloxan-induced diabetes mellitus, diabetes mellitus plus diet-induced dyslipidemia, and exercise-trained diabetic dyslipidemic pigs. The algorithms were developed for the porcine model because of several similarities to humans, including: cardiac anatomy and physiology, propensity for sedentary behavior, and metabolism of dietary carbohydrates and lipids. Acute toxic effects of alloxan (hypoglycemia, hyperglycemia, nephrotoxicosis) were minimized by preventive fluid loading and by use of algorithms in which insulin, food, and fluid therapy were administered. Long-term insulin and food maintenance algorithms elicited normal body weight gain in all three diabetic groups (lean experiment) and threefold greater body weight gain in pigs of an obesity experiment. Exercise-trained pigs of both experiments manifested significantly increased work performance and did not experience medical complications. We conclude that these algorithms can be used in swine, or similar algorithms can be developed for other animal species to maintain hyperglycemia and/or dyslipidemia, while avoiding diabetes-induced wasting. Importantly, animal models of diabetes mellitus that maintain positive energy balance and poor glycemic control provide a marked improvement over other models by more closely mimicking the human presentation of diabetes mellitus.
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PMID:Porcine model of diabetic dyslipidemia: insulin and feed algorithms for mimicking diabetes mellitus in humans. 1262 6


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