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

In the lens, disorders of the metabolism occur, and, with them, active permeability (the cation pump with uptake of K and release of Na) changes to passive permeability and consequently Na ions enter with water. As a result, the lens increases in weight and a subcapsular (permeability) cataract develops. It is shown that the cattle lens in vitro increases in weight the lower the pH (6.5 greater than 7.5 greater than 8.5) of the surrounding fluid becomes. In a further experiment, 1 ml of buffered liquids with different pH were injected into the anterior chamber of the eyes of freshly slaughtered cattle. Here, too, the mechanically undamaged, untouched lens increased in weight more greatly as the pH (5.5 greater than 6.5 greater than 7.5 greater than 8.5) of the injected fluid was lowered. The significance of the lowering of the pH, e.g., in local inflammation (iritis, cyclitis, retinitis, etc.) or general acidoses (diabetes mellitus, galactosemia, hunger, extracorporeal circulation for atrophic kidney. Albright-, Love-, Fanconi-syndrome) for the appearance of incipient subcapsular clouding of the lens is pointed out.
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PMID:[Lens changes occuring as a result of lowered pH (acidosis) (author's transl)]. 1 65

1. Glucokinase is one of four glucose phosphorylating enzymes present in rat liver. Its distinctive features are a high K-m for glucose (high-K-m isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-K-m isozymes, exhibit low K-m values for glucose and a wider substrate specificity. 2. Glucokinase is present in the liver os mammals (with some exceptions), amphibians and lower reptiles; It is absent from higher reptiles and birds. The presence or absence of glucokinase may represent an evolutionary adaptation to feeding habits and other physiological peculiarities. Differences in the immunological behavior and in the kinetic parameters of glucokinases from different taxa suggest the operation of divergent evolution. 3. The levels of glucokinase in rat liver depend strictly on the supply of carbohydrate in the diet. Glycogen phosphorylase and glycogen synthetase behave similarly, whereas other carbohydrate-metabolizing enzymes depend on the provision of either protein or protein plus carbohydrate. Glucokinase decays with a half-life of 33 hr when rats are starved or fed a carbohydrate-free diet, and is induced by the administration of glucose. The adaptive character is not exhibited by all mammals, indicating evolutionary discrimination within the same class and even within the same single order Rodentia. Enzyme adaptation in the liver may partially explain the condition known as 'hunger diabetes'. 4. The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction. Glucocorticoids and some pituitary hormones modulate the rate of induction. The mechanisms underlying the hormonal regulation of glucokinase levels are not well known. 5. The variations in liver glucokinase correspond to changes in the amount of enzyme protein as assessed by immunochemical titration. This fact agrees with the effects of inhibitors of protein synthesis on glucokinase induction. 6. An antiserum against rat glucokinase reacts with the enzyme from mammals and turtles but not with the amphibian enzyme. It does not react with low-K-m hexokinases from different sources. 7. The saturation function for glucose is sigmoidal in mammalian and amphibian glucokinases but not in glucokinase from lower reptiles. The Hill's coefficient is very constant with values about 1.6. The K0.5 (concentration for half saturation) values in the different species studied vary between 1.5 and 8 mM. These kinetic parameters may be considered as another adaptive feature aimed to give maximal efficiency to the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose.
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PMID:Adaptive character of liver glucokinase. 16 20

Lipoatrophic diabetes has been produced in rabbits by injection of a fraction prepared from the urine from patients with congenital generalized lipodystrophy. Both these conditions are considered to be hypothalamic syndromes. The animals, and a patient with congenital generalized lipodystrophy and latent diabetes were treated with the dopamine receptor blocker, pimozide, for 4 and 17 months, respectively. The results were discouraging even though the patient got a daily dose of 16 mg pimozide. Fenfluramine has a lowering effect on brain serotonin, and peripheral effects on glucose and triglyceride metabolism. This drug improved the general condition of the rabbits with lipoatrophic diabetes, as well as that of the patient with congenital generalized lipodystrophy. The rabbits became normoglycaemic and insulin sensitive. In the patient a normalization of the urinary excretion of the serotonin metabolite 5-OH-indole acetic acid was observed. His voracious hunger and profuse perspiration were reduced, the hyperkeratotic layer of the skin peeled off, and the pigmentations of the skin decreased. There was observed an improvement of ALAT and ASAT, normalization of the fasting blood glucose, and increased sensitivity to exogenous insulin. After 11 months of 200 mg fenfluramine daily addtitional administration of 2 g clofibrate per day produced normalization of the serum triglyceride concentration and a marked reduction of the resistance to insulin. Three more patients with congenital generalized lipodystriphy, two of whom have manifest diabetes, have now started treatment with fenfluramine and are improving. The rabbits got relapse of their lipoatrophic diabetes when the fenfluramine treatment was stopped. It is suggested that a disturbance in the serotonin metabolism of the central nervous system may be of pathogenetic importance in congenital generalized lipodystrophy.
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PMID:Congenital generalized lipodystrophy and experimental lipoatrophic diabetes in rabbits treated successfully with fenfluramine. 57 33

Congenital generalized lipodystrophy is considered to be a diencephalic syndrome with disturbance of hypothalamic transmitters. After puberty and arrest of growth the patients develop a serious untreatable diabetes mellitus. One of our patients, a girl 15 years of age, developed a lipodystrophic diabetes with fasting blood glucose levels above 300 mg/100 ml, increased serum insulin with insulin resistance, and hyperlipidaemia. Daily administration of fenfluramine gave a dramatic improvement. The voracious hunger and profuse perspiration were reduced, the patient's serum lipids became normal, her blood glucose fell, and her sensitivity to exogenous insulin increased. A normalization of the urinary excretion of the serotonin metabolite, 5-OH-indole acetic acid, was observed.
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PMID:Lipodystrophic diabetes treated with fenfluramine. 61 40

Four adolescents or young adults with the Prader-Willi syndrome (hypotonia, mental retardation, hypogonadism and obesity) received a protein-sparing modified fast consisting of 1.5 g of meat protein per kilogram of ideal body weight and meeting vitamin, mineral and fluid requirements. Evaluation of nitrogen and energy metabolism revealed the development of starvation ketosis and a positive nitrogen balance. Serial whole-body potassium measurements in two patients confirmed preservation of lean tissue despite continuing loss of weight. Clinical diabetes mellitus in two subjects was rapidly ameliorated by the regimen. Short-term weight loss greater than 18 kg occurred in three of the four subjects, and reduced weight persisted during observation periods of 26 to 44 months. This degree of outpatient diet adherence by mentally deficient subjects, who do not normally experience satiety, suggests that hunger is eliminated or at least reduced by modified, protein-sparing fasting.
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PMID:Metabolic aspects of a protein-sparing modified fast in the dietary management of Prader-Willi obesity. 84 Feb 78

Very fat people die earlier than people of normal weight because hypertension, diabetes and coronary disease are more frequent among the markedly obese. Most obese subjects, however, are only slightly overweight and their mortality is not elevated. Reasons for dieting are more often psychological than somatic. 2. Reducing diets are ineffective because the obese rarely follow them. Total fasting and intestinal bypass may provide better results, but are more dangerous. 3. Atkins' diet eliminates carbohydrates from food without restricting protein and fat intake. Deprived of carbohydrates, the body uses fat for fuel. A small part of metabolized fat is eliminated in the urine as ketone bodies, and this is why such diets are called "ketogenic". They have been known at least since 1863. 4. Caloric loss due to ketonuria does not exceed 100 Cal/day in the non-diabetic. It is maximal during total fasting and cannot be increased by a ketogenic diet. 5. In the short run, such diets produce rapid weight loss due to polyuria. On the other hand, refeeding carbohydrates causes water retention and weight gain. 6. The diet decreases appetite: patients eat less without feeling severe hunger and without measuring their food intake. 7. Orthostatic hypotension, fatigue, and nausea are frequent, despite what Dr. ATKINS claims. 8. The diet increases plasma cholesterol and uric acid. It may be dangerous in diabetes (anorexia, acidosis) and in heart or kidney failure (hypokalemia). 9. The diet, though far from good, is better than the book. ATKINS' theories are at best half-truths, and the results he claims lack credibility. The obese subject's disappointment with traditional reducing diets and the book's hard-sell style account for ATKINS' success.
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PMID:[Dr. Atkins' dietetic revolution: a critique]. 89 45

A protein-sparing modified fast (PSMF), which is a total fast modified by the intake of 1.2-1.4 gm. protein per kilogram ideal body weight (IBW), fluids ad libitum, and vitamin and mineral supplementation, allows effective control of carbohydrate metabolism and hunger. It reduces serum glucose and insulin concentrations in obese diabetic patients and increases free fatty acid and ketone body concentrations; ketonuria appears within 24-72 hours. When this fast was applied to seven obese adult-onset diabetics who were receiving 30-100 units of insulin per day, insulin could be discontinued after 0-19 days (mean, 6.5). In the three patients who had extensive nitrogen-balance studies, balance could be maintained chronically by 1.3 gm. protein per kilogram IBW, despite the gross caloric inadequacy of the diet. The PSMF was tolerated well in an outpatient setting after the initial insulin-withdrawal phase had occurred in the hospital. Significant improvements in blood pressure, lipid abnormalities, parameters of carbohydrate metabolism, and cardiorespiratory, symptoms were associated with weight loss and/or the PSMF. For diabetics with some endogenous insulin reserve, the PSMF offers significant advantages for weight reduction, including preservation of lean body mass (as reflected in nitrogen balance) and withdrawal of exogenous insulin.
Diabetes 1976 Jun
PMID:Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast. 127 1

We tested the hypotheses that nonselective beta-adrenergic blockade does not cause absolute hypoglycemia unawareness but shifts the glycemic thresholds for symptoms to lower plasma glucose concentrations and that neither neuroglycopenic symptoms nor cognitive impairments during hypoglycemia are altered by beta-adrenergic blockade. To do so, we applied the euglycemic and stepped hypoglycemic clamp techniques to patients with moderately controlled insulin-dependent diabetes mellitus (IDDM) in the absence (n = 8) and presence (n = 9) of the nonselective beta-adrenergic antagonist propranolol. Compared with the corresponding euglycemic clamps, total symptom scores first increased at the 4.4-mM plasma glucose step (a higher level than that of 2.8 mM in nondiabetic subjects studied previously) in the absence of propranolol. Beta-adrenergic blockade did not produce absolute hypoglycemia unawareness. Indeed, at the frankly hypoglycemic step of 2.8 mM, total symptom scores tended to be higher in the presence than in the absence of propranolol. This was largely the result of greater (P less than 0.01) perception of diaphoresis. However, symptom scores did not increase until the 3.3-mM plasma glucose step during beta-adrenergic blockade. The perception of hunger, and perhaps that of tremulousness, was reduced by propranolol at the higher glucose steps. Neuroglycopenic symptoms were not reduced by propranolol. The cognitive function of memory, but not that of attention, was impaired, also starting at the 4.4-mM glucose step. This was not impaired further by propranolol. Thus, we formed the following conclusions. 1) Nonselective beta-adrenergic blockade does not cause absolute hypoglycemia unawareness but shifts the glycemic thresholds for symptoms to lower plasma glucose concentrations in patients with IDDM. 2) Beta-adrenergic blockade does not reduce neuroglycopenic symptoms, and it does not further impair cognitive function during hypoglycemia in IDDM patients.
Diabetes 1991 Sep
PMID:Higher glycemic thresholds for symptoms during beta-adrenergic blockade in IDDM. 165 73

Not all episodes of hypoglycemia are recognized as such by diabetic patients, suggesting that it is possible for them to adapt to a low blood glucose level, although the mechanism involved is not known. The aim of this study was to examine whether insulin has an effect, independent of blood glucose, on the subjective, cognitive, and hormonal responses to hypoglycemia. Nine patients with insulin-dependent diabetes mellitus (IDDM) participated in three hyperinsulinemic glucose-clamp studies. After 60 min at 4.5 mM, blood glucose was randomized to be 1) maintained at 4.5 mM for 240 min, 2) lowered to 2.8 mM for 180 min followed by 60 min at 2 mM with an insulin infusion rate of 40 mU.m-2.m-1, and 3) fitted to the same protocol as 2 but with an infusion rate of 120 mU.m-2.min-1. Symptoms and awareness of hypoglycemia (100-mm visual analogue scales), cognitive function, and counterregulatory hormone levels were assessed every 30 min. There were no subjective or cognitive changes during the euglycemic study. Awareness and hypoglycemic symptoms (hunger, facial flushing, trembling, and sweating) were attenuated by the higher insulin infusion rate (P less than 0.05 and P less than 0.01, respectively). Cognition was significantly impaired after 60 min at 2.8 mM (P less than 0.001) and deteriorated further when the blood glucose level was lowered to 2 mM (P less than 0.01). Levels of cortisol (P less than 0.01) and growth hormone (P less than 0.05) but not epinephrine were suppressed by the higher insulin infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Aug
PMID:Importance of insulin in subjective, cognitive, and hormonal responses to hypoglycemia in patients with IDDM. 186 May 57

It has been reported over the last few years that transferring diabetic patients from animal to human insulin can lead, in some of the patients, to a diminution of the classical hypoglycaemic symptoms, as hunger and sweating, and to the more frequent occurrence of neuroglycopenic symptoms, as the first manifestation of hypoglycaemia. These changes seem to involve a fraction of patients estimated between 8 and 36%, depending on the type of selection of the patients. A decrease in the adrenergic counterregulatory response to hypoglycaemia has also been shown in some studies with human insulin. Similar changes in the sequence of hypoglycaemic symptoms are also described in various clinical conditions--as intensive insulin therapy with tight glycaemic control, long diabetes duration and presence of autonomic neuropathy, thus acting as confounding factors. According to these facts, a few recommendations are proposed: briefly, human insulin should only be prescribed to new patients who are able to learn from the very beginning the sequence of hypoglycaemic symptoms with human insulin; patients already treated with porcine insulin should not be transferred to human insulin. On the whole, studies available to date have not shown an increased frequency of severe hypoglycaemia with human insulin; however, this important matter still has to be conclusively clarified through well-designed prospective studies.
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PMID:[Human insulin and hypoglycemia]. 223 55


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