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Query: UMLS:C0011849 (diabetes)
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Alloxan-induced diabetes of 4 days duration produced metabolite changes in brain compatible with severe reduction in cerebral metabolism (phosphocreatine increased 70%), and reduced phosphofructokinase activity (fructose diphosphate levels fell 38%). There was a 56% reduction in brain lactate concentration, but pyruvate levels were unchanged. In 5 of 23 animals, brain glycogen levels increased; in the remainder blycogen levels decreased. Brain fructose concentration, 0.4 mmol/kg, was only 1/30 of the glucose concentration. The alloxan-treated animals were also severely dehydrated. Therefore, to determine the casual relation of insulin deficiency to these findings, the effects of chronic dehydration and acute insulin deficiency were investigated. Findings in the brains of severely dehydrated animals (water deprivation and mannitol injections for 4 days) were almost identical with those seen after alloxan treatment. The exceptions were that, in the dehydrated mice, reductions in lactate and pyruvate were proportional, and glycogen levels were consistently reduced. In acute diabetes (6 to 24 hours after repeated anti-insulin serum injections) P-creatine, fructose diphosphate, and lactate levels were normal. Pyruvate levels were normal at 6 hours, but increased 39% by 12 to 24 hours; glycogen was 36% higher at 6 hours and 63% at 12 to 24 hours. Insulin (and glucose) appeared to be specific in correcting the metabolic abnormalities found in the brains of animals with alloxan-induced diabetes. At 4 and one half hours after treatment with insulin and glucose, glucose 6-phosphate levels fell 25%, fructose diphosphate increased 28%, and lactate and the lactate to pyruvate ratio returned to normal; glycogen increased 50%. However, the treatment also had a dramatic clinical effect. Since animals gained 8 to 27% of body weight during therapy, at least some of the improvements in metabolite levels could be related to rehydration.
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PMID:Effects of alloxan diabetes, anti-insulin serum diabetes, and non-diabetic dehydration on brain carbohydrate and energy metabolism in young mice. 111 28

Serial changes in body composition during pregnancy have been measured in 5 normal and 2 diabetic women on controlled diets to compare with simultaneous measurements of oxygen consumption (V-O2). Total body water (TBW) was measured by D2O dilution, total body fat (TBF) calculated as 100-%TBW/0.732 and body cell mass (BCM) derived from total body 40K count by Moore's formula, BCM equals K-e times 8.33. Two normal subjects in caloric equilibrium lost 1.2 kg TBF, gained 5.5 kg TBW and 4.1 kg BCM. Two obese subjects in negative caloric balance lost 4.7 kg TBF, gained 7.3 kg TBW and 4.3 kg BCM. One subject on ad lib diet gained 7.7 kg TBF, 0.6 kg TBW, and 2.6 kg BCM. She continued to gain fat postpartum. Two diabetic subjects gained fat up to 28 weeks, lost it thereafter, and showed no net gain in BCM. Basal V-O2 correlated with BCM, while 24-hour resting V-O2 related to total body weight. It is concluded that fat storage in human pregnancy depends on food intake, as in the nonpregnant. BCM accumulation is independent of food intake, except protein, and depends on normal physiologic adjustments of pregnancy, which are upset by insulin lack in diabetes. The extra basal energy needs of gestation are determined by BCM acquisition, not total body weight.
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PMID:Changes in total body composition during normal and diabetic pregnancy. Relation to oxygen consumption. 112 65

The effects of low-mineral content water (Adelholzener Primus-Quelle) in 62 patients were studied of which 14 were hypertonic. Changes of blood sodium, potassium, chloride and bicarbonate were not observed in either group. In the hypertonic patients, blood pressure decreased from a mean systolic value of 168 to 140 mmHg and mean distolic pressure from 105 to 88 mmHg. Observations to date suggest the following indications for a low-mineral content water diet: 1. hypertension, 2. renal insufficiency in stages of compensated and decompensated retention, especially in cases with high serum potassium levels, 3. in the initial therapy of diabetes, gout and obesity; patients with a high water demand should be treated with low-mineral content water until the optimal intake of electrolytes is established.
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PMID:[Effects of water with a low mineral content on serum electrolytes and blood pressure]. 122 36

Alloxan-diabetic rats with fasting blood glucose levels above 300 mg./100 ml. were treated with intrajejunal administration of water-in-oil-in-water (W/O/W) insulin emulsions via an indwelling catheter at a dose of either 25 or 50 U./100 gm. body weight, three times daily for five to fourteen days. The course of diabetes was followed by determinations of glucose levels in blood and urine. During treatment a significant reduction in urinary glucose levels was observed in all rats studied. In two rats treated with 25 U./100 gm., fasting blood glucose levels did not change significantly. In four of five rats treated with 50 U./100 gm., W/O/W insulin emulsions significantly lessened hyperglycemia during treatment. Quantitative estimates suggested that the effectiveness of 50 U./100 gm. of intrajejunal W/O/W insulin emulsions was comparable to that after intramuscular regular insulin at doses between 1 and 2 U./100 gm. These results would indicate that diabetes can be controlled by enteral administration of insulin preparations.
Diabetes 1975 Nov
PMID:Short-term treatment of alloxan-diabetic rats with intrajejunal administration of water-in-oil-in-water insulin emulsions. 123 36

Incorporation of radiolabeled precursors into muscle proteins was studied in isolated rat hemidiaphragms. A mixture of three branched-chain amino acids (0.3 mM each) added to media containing glucose stimulated the incorporation of [14C]lysine into proteins. When tested separately, valine was ineffective, isoleucine was inhibitory, but 0.5 mM leucine increased the specific activity of muscle proteins during incubation with [14C]lysine or [14C]acetate in hemidiaphragms from fed or fasted rats incubated with or without insulin. Preincubation with 0.5 mM leucine increased the specific activity of muscle proteins during a subsequent 30- or 60-min incubation with [14C]lysine or [14C]pyruvate without leucine. Preincubation with other amino acids (glutamate, histidine, methionine, phenylalanine, or tryptophan) did not exert this effect. When hemidiaphragms were incubated with a mixture of amino acids at concentrations found in rat serum and a [14C]lysine tracer, the specific activity of muscle proteins increased when leucine in the medium was raised from 0.1 to 0.5 mM. Experiments with actinomycin D and cycloheximide suggested that neither RNA synthesis nor protein synthesis are required for the initiation of the leucine effect. Leucine was not effective when added after 1 h preincubation without leucine. The concentration of lysine in the tissue water of diaphragms decreased during incubation with 0.5 mM leucine in the presence or absence of cycloheximide, suggesting that leucine inhibited protein degradation. During incubation with [3h]tyrosine (0.35 mM) the addition of 0.5 mM leucine increased the specific activity of muscle proteins, while the specific activity of intracellular tyrosine remained constant and its concentration decreased, suggesting that leucine also promoted protein synthesis. The concentration of leucine in muscle cells or a compartment thereof may play a role in regulating the turnover of muscle proteins and influence the transition to negative nitrogen balance during fasting, uncontrolled diabetes, and the posttraumatic state. Leucine may play a pivotal role in the protein-sparing effect of amino aicds.
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PMID:Leucine. A possible regulator of protein turnover in muscle. 123 98

Seventy-eight critically ill patients who died while on the neurosurgical service were studied retrospectively to establish the prevalence of nonketotic hyperglycemic hyperosmolar coma (NHHC). All the patients had been comatose before death, and all underwent necropsy. Criteria for the diagnosis of NHHC included moderate-to-severe hyperglycemia with glucosuria, absence of significant acetonuria, hyperosmolarity with dehydration, and neurological dysfunction. This study revealed seven cases of unequivocal NHHC (9%), and six of hyperosmolarity but with incomplete records. Five of the seven confirmed cases of NHHC demonstrated no evidence of cerebral edema transtentorial herniation, or brain-stem damage, and showed central nervous system (CNS) lesions compatible with survival. Fatal complications of this syndrome, such as acute renal failure, terminal arrhythmias, and vascular accidents, both cerebral and systemic, were common in this series. The mechanism of coma in NHHC is believed related to shifts of free water from the cerebral extravascular space to the hypertonic intravascular space, with subsequent intracellular dehydration, accumulation of metabolic products of glucose, and brain shrinkage. It is uncertain whether injury to specific areas in the CNS is a predisposing factor to the development of NHHC. Factors documented to be significant in its development include nonspecific stress to primary illnesses, hyperosmolar tube feedings, dehydration, diabetes and mannitol, Dilantin, or steroid administration.
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PMID:Nonketotic hyperglycemic hyperosmolar coma. Report of neurosurgical cases with a review of mechanisms and treatment. 125 32

Statistics from various studies are compiled to present an overview of the somatic complications of induced abortions. These complications are divided into 2 groups, the 1st consisting of ''early'' complications that arise during the abortion or for 30 days afterwards. From 1970 to 1974, 1-9 deaths/100,000 induced abortions are registered in studies from various countries. A study from England and Wales shows that patient deaths after abdominal uterotomy are 3-9 times more numerous than vacuum and instrumental evacuation of the uterus and that abortions performed after the 12th week are 1.25-4.0 times more prevalent than during the first 12 weeks. ''Early'' complications are then divided into 2 categories, ''serious complication,'' e.g., uterine perforation, loss of blood requiring a transfusion, and ''complication'' exemplified by pyrexia. In various studies from throughout the world, ''complications'' arose in 4-25.6% of the cases and ''serious complications'' in 1.1-7.6%. In women with a somatic illness (e.g., diabetes) during an abortion, a greater percentage have complications. Patients having extirpation of the uterus, uterotomy, and sterilization, or salt water instillation had at least 3 times as many complications as those having vacuum aspiration or dilatation and curettage. The 2nd type of complication, the ''late'' complications, are permanent (e.g., sterility), or occur 30 days after the abortion (e.g., endometriosis). These complications are generally poorly documented and researched. The frequency of sterility as a ''late'' complication ranges from 1-6% in 1 study to 53% in another. There are indications that previous induced abortion can cause premature birth or spontaneous abortion, although there is contradicting evidence. These ''late'' complications are caused by cervical insufficiency caused by the induced abortion. More documentation is needed to make statements about the ''late'' complications.
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PMID:[Somatic complications following induced abortions]. 125 10

The oxidation of leucine by hemidiaphragms of control and diabetic rats was studied in vitro. Rats were rendered diabetic with streptozotocin. Hemidiaphragms of diabetic rats produced approximately 50% more 14CO2 during incubation with 0.1 mM [1-14C]leucine than did control muscles. This was observed during incubation with or without glucose and in the presence or absence of a full complement of plasma amino acids. The concentration of leucine in the tissue water of hemidiaphragms from diabetic rats was greater than that in the control muscles before incubation. The specific activity of leucine at the end of 60 min incubation was not significantly different in diabetic and control muscles, indicating that the increased 14CO2 production represented stimulation of leucine oxidation. Hemidiaphragms of diabetic rats released more leucine into the medium during incubation than did control muscles. The stimulating effect of diabetes on leucine oxidation in vitro was reversible by insulin therapy prior to sacrifice. The addition of 5 mM pyruvate to a medium containing glucose inhibited 14CO2 production from [14C]leucine in control muscles, but stimulated leucine oxidation by hemidiaphragms of diabetic rats. Leucine oxidation by hemidiaphragms of diabetic rats was markedly stimulated by the addition of an electron acceptor, 0.02 mM methylene blue, suggesting that the NADH/NAD ratio may be rate-limiting for branched chain amino acid oxidation in muscles of diabetic rats, but not in muscles of controls. We suggest that the accelerated oxidation of branched chain amino acids by muscles may play a role in the acceleration of the muscle protein catabolism and gluconeogenesis which develop during insulin deficiency. The restraining effect of the cellular redox potential on branched chain amino acid oxidation may play a role in the eventual deceleration of protein catabolism during a prolonged fast.
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PMID:The effect of diabetes, insulin, and the redox potential on leucine metabolism by isolated rat hemidiaphragm. 126 11

Morphometric analysis of pancreatic islets was performed on BB/W rats, which were divided into moderately diabetic and severely diabetic as well as normoglycemic during four months of observation. In normoglycemic rats, total islet area occupied 1.2% of total pancreatic tissue area with a mean area of 19,000 microns2 per islet. Total pancreatic area was markedly decreased to 22% and 10% in moderately and severely diabetic rats, respectively, compared with that of normoglycemic rats. Mean islet area of moderately and severely diabetic rats decreased to 28% and 25% per islet that of normoglycemic rats, respectively, in which severely diabetic rats showed variable sizes of islets. Concomitant morphometric analysis of renal glomeruli showed decreasing sizes of glomeruli in severely diabetic rats whereas number of glomeruli in renal cortex increased in severely diabetic rats compared with normoglycemic rats. Moderately and severely diabetic states were also studied by I.V. glucose and insulin tolerance tests in regard to plasma glucose and insulin levels compared with normoglycemic rats. During months of observation severely diabetic rats had their total islet area reduced to 10% that of normoglycemic rats as a result of cell mediated immune destruction of islets. And concomitant reduction of glomeruli may be a part of diabetic glomerulopathy. Yet, diabetic rats were normotensive. The degree of water intake, urine volume, urine glucose, urine protein and albumin was also correlated with the degree of diabetes. This study further provides the feasibility of using diabetic BB/W rats for diabetic conditions and their complications.
Diabetes Res 1992 Feb
PMID:Correlation of morphometric analysis of pancreatic islets and diabetes in spontaneously diabetic BB/W rats. 128 39

Water-soluble group B vitamins metabolism was studied over the course of streptozotocin-induced diabetes mellitus in rats fed semisynthetic isocaloric diets containing 18 and 50% of protein. A high-protein diet in diabetes mellitus does not influence riboflavin metabolism disordered in this disease but reduced 4-pyridoxyl acid excretion to the level characteristic of healthy animals. The observed trend to an increase of liver nicotinamide coenzymes levels and of 1-methylnicotinamide urinary excretion reflects increased niacin synthesis from the diet protein tryptophan, for niacin level is reduced in diabetes.
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PMID:[Effect of protein content in rat diet on water-soluble vitamin metabolism in streptozotocin-induced diabetes]. 130 52


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