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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Energy stores and intermediates of carbohydrate metabolism were investigated in the freeze-clamped cerebral cortex of the fetus and fasted neonate born to a diabetic canine mother. Prior studies in these same pups demonstrated circulating hyperinsulinemia, depressed free fatty acid levels, and attenuated gluconeogenesis. Hepatic and muscle tissue also demonstrated augmented levels of glycogen, triglycerides, and amino acids. In the present investigation, cerebral tissue from these same pups of diabetic mothers also demonstrated enhanced fetal cerebral glucose and glycogen content. After 24 h of neonatal fasting, cerebral glycogen content declined to values lower than in control pups. Cerebral cortical levels of glucose-6-phosphate, fructose-6-phosphate, lactate, citrate, alpha-ketoglutarate, and malate were not altered, while oxaloacetate was higher at 3 and 9 h and fructose-1,6-diphosphate was higher at 9 and 24 h in the IDM pups. Adenine nucleotide levels and the energy charge were equivalent to those in control pups at each time interval. In contrast, cerebral cortical amino acids of the glutamate group were enhanced in the fetus or neonate of the diabetic mother. Cerebral cortical alanine was increased from 3 to 24 h while aspartate and glutamate were augmented in the fetus and fasted IDM newborn pup. Glutamine was increased at 6 and 24 h, while gamma-aminobutyrate was elevated in the fetus. Cerebral ammonia concentration was not altered. The augmented stores of cerebral carbohydrate and amino acid pools in the fetus and neonate after maternal canine diabetes may serve as oxidizable substrates for the brain during periods of attenuated systemic fuel availability.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Feb
PMID:Enhanced cerebral substrate pools in the fetus and neonate of the diabetic canine mother. 285 42

1. In short- and long-term diabetic rats there is a marked increase in size of both the small intestine and colon, which was accompanied by marked decreases (P less than 0.001) and increases (P less than 0.001) in the arterial concentrations of glutamine and ketone bodies respectively. 2. Portal-drained viscera blood flow increased by approx. 14-37% when expressed as ml/100 g body wt., but was approximately unchanged when expressed as ml/g of small intestine of diabetic rats. 3. Arteriovenous-difference measurements for ketone bodies across the gut were markedly increased in diabetic rats, and the gut extracted ketone bodies at approx. 7 and 60 nmol/min per g of small intestine in control and 42-day-diabetic rats respectively. 4. Glutamine was extracted by the gut of control rats at a rate of 49 nmol/min per g of small intestine, which was diminished by 45, 76 and 86% in 7-, 21- and 42-day-diabetic rats respectively. 5. Colonocytes isolated from 7- or 42-day-diabetic rats showed increased and decreased rates of ketone-body and glutamine metabolism respectively, whereas enterocytes of the same animals showed no apparent differences in the rates of acetoacetate utilization as compared with control animals. 6. Prolonged diabetes had no effects on the maximal activities of either glutaminase or ketone-body-utilizing enzymes of colonic tissue preparations. 7. It is concluded that, although the epithelial cells of the small intestine and the colon during streptozotocin-induced diabetes exhibit decreased rates of metabolism of glutamine, such decreases were partially compensated for by enhanced ketone-body utilization by the gut mucosa of diabetic rats.
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PMID:Glutamine and ketone-body metabolism in the gut of streptozotocin-diabetic rats. 289 6

Phosphoenolpyruvate carboxykinase (PEPCK) activity is present along the length of rat small intestine and in enterocytes throughout the villus-crypt axis. There is no detectable activity in submucosal layers. Messenger RNA encoding PEPCK is detectable in rat intestinal mucosa and the relative abundance increases markedly (3- to 8-fold) during starvation or streptozotocin-diabetes. However, these changes are not matched by changes in enzyme activity which are only slightly increased (1.5-fold). The intestine of neonatal rats possesses relatively high amounts of both PEPCK activity and mRNA. Based on the distribution and regulation of intestinal PEPCK, it is proposed that the enzyme does not play a significant role in either gluconeogenesis or glutamine catabolism in adult rats.
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PMID:Phosphoenolpyruvate carboxykinase of rat small intestine: distribution and regulation of activity and mRNA levels. 291

The liver is the "glucostat" of the organism and serves at the same time as an "ammonia-sink and pH stat". The key enzymes involved in glucose uptake and release and in urea and glutamine formation are reciprocally distributed over the liver parenchyma: The glucogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK), fructosebisphosphatase (FBPase) and glucose-6-phosphatase (G6Pase) as well as the ureagenic enzyme carbamoylphosphate synthetase (CAPS) are predominant in the periportal zone. The glycolytic enzymes glucokinase (GK) and pyruvate kinase type L (PKL) as well as the glutaminogenic enzyme glutamine synthetase (GluNS) are prevalent in the perivenous zone. This heterogeneity appears to be a prerequisite for the normal "glucostat, ammonia-sink and pH-stat" function of the liver. After birth the liver is a gluconeogenic organ, only with weaning it becomes a "glycolytic/gluconeogenic" glucostat. In the rat zonation of PEPCK, G6Pase and CAPS developed gradually after birth and was completed before weaning, i.e. before it would be functionally required. After 2/3 partial hepatectomy the liver looses its normal glucostat function and becomes a gluconeogenic organ. With this change the zonation of PEPCK and PKL were also lost; it was restored only during the second week after operation. During starvation the liver also looses its glucostat function to become the major glucose supplier of the organism. Zonation of PEPCK and PKL were diminished to such an extent that the major function of the perivenous zone was altered from glucose uptake to release. In diabetes the liver does not loose its glucostat function; however, the function is severely impaired. Zonation of PEPCK was increased and that of PKL decreased in such a manner that the major function of the perivenous zone, glucose uptake, was not entirely changed but only diminished. It can be concluded that in the various physiological states studied the zonation of enzymes correlated well with the glucostat function of the liver.
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PMID:Dynamics of zonal hepatocyte heterogeneity. Perinatal development and adaptive alterations during regeneration after partial hepatectomy, starvation and diabetes. 301 Mar 76

The intestine is capable of shifting its major fuel source from glutamine in the fed animal to ketone bodies in the fasted animal. Glutaminase (EC 3.5.1.2), the entry enzyme of glutamine oxidation, was examined for its function as a determinant in the utilization of jejunal fuel during diabetes and fasting. Male Sprague-Dawley rats were made ketotic to varied degrees by either fasting or the induction of diabetes with graded doses of streptozotocin (SZ). Specific activity of glutaminase was decreased in the diabetic animals to 64% (p less than 0.05) of controls in the group receiving 110 mg/kg SZ and 82% of controls in the group receiving 65 mg/kg SZ and to 78% (p less than 0.05) of controls in the fasted animals. The activity of glutaminase in the small intestine was negatively correlated to the concentration of beta-hydroxybutyrate in the plasma (r = -0.97, p less than 0.025) and jejunum (r = -0.92, p less than 0.05) for the four groups of animals. Specific activity of glutaminase was decreased in all cell types isolated along the villus-crypt axis of the small intestine from diabetic and fasted rats compared with control rats. The quantity of glutaminase-protein was determined by a dot immunobinding assay using an antibody to purified glutaminase. The activity of glutaminase relative to immunoreactive glutaminase-protein was significantly decreased (p less than 0.05) to 53% of control values in the 110 mg/kg SZ group, 77% in the 65 mg/kg SZ group, and 70% in the fasted group. These data indicate that an inactivation of glutaminase-protein may play a role in the ability of the intestine to shift its fuel source from glutamine to ketone bodies during diabetes and fasting.
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PMID:Effect of diabetic ketosis on jejunal glutaminase. 308 69

The transport specificity of L-glutamine influx in the perfused rat exocrine pancreas has been investigated using a dual isotope tracer dilution technique. During a single circulation through the isolated pancreas, an epithelial uptake of 71 +/- 1% (n = 10) was measured for L-(3H)glutamine relative to the extracellular marker D-(14C)mannitol. L-(3H)glutamine uptake was markedly inhibited during perfusion with 10 mM L-glutamine, L-histidine, L-methionine, L-serine, or L-cysteine. The system A--specific analogue alpha-methylaminoisobutryic acid and L-glutamic acid were ineffective inhibitors. L-Glutamine transport was saturable (0.05 - 32 mM), with an apparent Kt = 14 +/- 1 mM and Vmax = 13.4 +/- 0.7 mumol/min g (n = 6), and largely insensitive to perfusion with 1 mM ouabain or a sodium-free solution. In kinetic inhibition experiments, the Vmax/Kt ratio for L-glutamine remained unaltered during perfusion with 10 mM L-serine, whereas L-glutamine appeared to inhibit L-serine transport noncompetitively. Tracer L-glutamine efflux was enhanced by increasing concentrations of unlabeled L-glutamine and 10 mM L-serine. Similarly, tracer L-serine efflux was accelerated in the presence of 10 mM L-glutamine. Unlike L-serine, the transport activity for L-glutamine was not stimulated by 100 microU/ml exogenous insulin or streptozotocin-induced experimental diabetes. These findings suggest that in the exocrine pancreas, L-glutamine transport is mediated primarily by a large neutral system L.
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PMID:Characteristics of L-glutamine transport in the perfused rat exocrine pancreas: lack of sensitivity to insulin and streptozotocin-induced experimental diabetes. 310 60

The serum amino acid spectrum was examined in healthy men and insulin-dependent diabetics from Ethiopia. Comparison of serum amino acids of controls from Gondar with Ethiopians after adaptation to a free European diet revealed a marginal low protein nutrition, but not the characteristic changes of malnutrition or experimental starvation. There was no apparent nutritional deficiency of sulphur-containing amino acids in Ethiopians. Insulin-dependent diabetics showed significantly elevated serum levels of BCAA indicating an accelerated protein catabolism in recent-onset insulin-deficient patients and known diabetics respectively, most of them in poor metabolic condition. Serum glutamine levels were reduced, suggesting a considerable renal contribution to the hyperglycaemia/glucosuria of diabetics. The data may be best explained by the low residual insulin secretion at diabetes onset or by the poor degree of metabolic control of known Ethiopian diabetics.
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PMID:The serum amino acid spectrum of insulin-dependent diabetics and controls from Ethiopia. 325 68

The purpose of this investigation was to collect data concerning changes in carbohydrate and amino acid metabolism following different surgical operations (thoracotomies, laparotomies). Blood of 20 metabolically healthy adult surgical patients, who had to undergo elective surgery (lobectomies, pneumonectomies, colon resections) was examined preoperatively, immediately postoperatively and from 1.-4.postoperative day. The experimental data during the perioperative phase showed a similar pattern in both groups of patients: We found a significant elevation in the blood glucose level and there was also a rise in plasma cortisol and plasma free fatty acids levels. We found no significant changes of blood lactate, plasma insulin and branched chain amino acids. Simultaneously we found a drop in plasma albumin, pre-albumin and some glucoplastic amino acids (ALA, GLN, THR, PRO). It is concluded that major abdominal and thoracic surgery give rise to a nonspecific stress situation reflected in carbohydrate and amino acid metabolism with the following metabolic symptoms: Raised lipolysis and gluconeogenesis, disturbance of glucose utilisation and obvious peripheral insulin resistance. These perioperative metabolic effects show some similarities to the metabolic situation in diabetes mellitus type 2.
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PMID:[Postaggression metabolism following laparotomy and thoracotomy]. 328 Feb 68

The effects of fasting, refeeding, and streptozotocin-induced experimental diabetes on free amino acid concentrations in the rat exocrine pancreas were investigated. Extracts of pancreatic tissue and plasma were analyzed using high-performance liquid chromatography (HPLC). Pancreatic and plasma concentrations of alanine were reduced in animals fasted for 24 to 72 h. Pancreatic concentrations of leucine, arginine, and glutamine were increased after fasting for 48 h, and concentrations of all essential amino acids plus the nonessential amino acids glycine, serine, taurine, and glutamine were elevated after fasting for 72 h. Refeeding 72 h fasted animals for 3 h or 24 h had a negligible effect on the plasma amino acid concentrations, but markedly lowered the concentration of essential amino acids within the pancreatic tissue. Diabetes lowered the total plasma amino acid concentration from 4.9 mM to 3.1 mM but increased the total pancreatic tissue amino acid level from 16.4 mM to 18.3 mM. Efflux of intracellular amino acids into the circulation of the isolated perfused pancreas was assessed under basal conditions and in response to a vascular amino acid challenge using HPLC. L-serine transstimulated efflux of a large number of amino acids, whereas cellular efflux was only minimally affected by L-phenylalanine. Fasting and diabetes-induced increases in essential amino acid concentrations within the pancreas may reflect decreased protein synthesis, accelerated protein catabolism, or a change in membrane transport. Altered intracellular amino acid levels may directly regulate exchange diffusion of intracellular for extracellular amino acid(s).
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PMID:Fasting, refeeding and diabetes modulate free amino acid concentrations in the rat exocrine pancreas: role of transstimulation in amino acid efflux. 336 44

The small intestine is the major site of glutamine utilization in the mammalian body. During prolonged (40-day) streptozotocin-diabetes in the rat there is a marked increase in both the size and the phosphate-activated glutaminase activity of the small intestine. Despite this increased capacity, intestinal glutamine utilization ceases in diabetic rats. Mean arterial glutamine concentration fell by more than 50% in diabetic rats, suggesting that substrate availability is responsible for the decrease in intestinal glutamine use. When arterial glutamine concentrations in diabetic rats were elevated by infusion of glutamine solutions, glutamine uptake across the portal-drained viscera was observed. The effect of other respiratory fuels on intestinal glutamine metabolism was examined. Infusions of ketone bodies did not affect glutamine use by the portal-drained viscera of non-diabetic rats. Prolonged diabetes had no effect on the activity of 3-oxoacid CoA-transferase in the small intestine or on the rate of ketone-body utilization in isolated enterocytes. Glutamine (2 mM) utilization was decreased in enterocytes isolated from diabetic rats as compared with those from control animals. However, glutaminase activity in homogenates of enterocytes was unchanged by diabetes. In enterocytes isolated from diabetic rats the addition of ketone bodies or octanoate decreased glutamine use. It is proposed that during prolonged diabetes ketone bodies, and possibly fatty acids, replace glutamine as the major respiratory fuel of the small intestine.
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PMID:The regulation of glutamine and ketone-body metabolism in the small intestine of the long-term (40-day) streptozotocin-diabetic rat. 347 86


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