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

1. The metabolism of [U-(14)C]glucose by the isolated diaphragm muscle of normal rats, rats rendered diabetic with streptozotocin and rats with transitory insulin deficiency after an injection of anti-insulin serum was studied. 2. The incorporation of [(14)C]glucose into glycogen and oligosaccharides was significantly decreased in the diabetic diaphragm muscle and in the muscle from rats treated with anti-insulin serum. 3. Neither diabetes nor transitory insulin deficiency influenced the oxidation of glucose, or the formation of lactate and hexose phosphate esters from glucose. 4. Insulin fully restored the incorporation of glucose into glycogen and maltotetraose in the diabetic muscle, but the incorporation into oligosaccharides, although increased in the presence of insulin, was significantly lower than the values obtained with normal diaphragm in the presence of insulin.
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PMID:The metabolism of glucose in diaphragm muscle from normal rats, from streptozotocin-treated diabetic rats and from rats treated with anti-insulin serum. 570 83

Arterial (A) and renal venous (RV) concentrations and net splanchnic exchange of glucose, fructose, lactate, pyruvate, glycerol, and alanine were studied in the basal state and during a 135-min intravenous infusion of fructose at 2 mmol/min in healthy subjects after a 60-h fast. After 45 min of the fructose infusion, somatostatin (9 microgram/min) was infused for 60 min to induce hypoglucagonemia. Fructose infusion resulted in a net uptake of this hexose by the kidney as well as the splanchnic bed. Estimated renal uptake of fructose could account for the disposal of 20% of the administered fructose load while splanchnic uptake accounted for 38%. The fructose infusion resulted in a rise in blood glucose of 0.9 mmol/L, a 35% increase in net glucose output from the splanchnic bed, and a consistent net output of glucose from the kidney (A-RV = -0.17 +/- 0.05 mmol/L as compared with 0 +/- 0.03 in the basal state, P less than 0.02). Net glucose release from the kidney could account for 55% of the net renal uptake of fructose. The fructose infusion also resulted in a marked change in renal lactate balance from a net uptake in the basal state (A - RV = 0.05 +/- 0.01 mmol/L) to a net output during fructose administration (A - RV = -0.10 +/- 0.04). Administration of somatostatin resulted in a fall in arterial glucagon levels and a 35% decrease in splanchnic glucose output but failed to alter the arterial-renal venous difference for glucose observed during the fructose infusion. We conclude that in 60-h fasted man: (a) intravenous infusion of fructose results in a net uptake of this hexose by the kidney as well as the liver, (b) this uptake is accompanied by stimulation of renal as well as hepatic glucose production and renal production of lactate, and (c) hypoglucagonemia inhibits splanchnic but not renal glucose output during fructose infusion. These data indicate that the kidney is an important site of fructose disposal and that glucose and lactate are end products of renal fructose metabolism.
Diabetes 1982 Jun
PMID:Role of the kidney in the metabolism of fructose in 60-hour fasted humans. 613 22

To study the glycosylation of glomerular basement membrane collagen (GBMC) in diabetes, kidneys were obtained at autopsy from 5 patients with insulin-requiring diabetes of long duration and diabetic complications, and from 5 control subjects. Glomeruli were prepared by sieving and collagen was isolated by limited pepsin proteolysis followed by salt precipitations. Amino acid analyses of the collagen preparations, after acid hydrolysis, indicated a composition consistent with that of type IV collagen. No differences in the relative contents of various amino acids, and in particular, 3-hydroxyproline, 4-hydroxyproline and hydroxylysine, were noted between diabetic and control samples. Non-enzymatic glucosylation was assessed by measuring hexose in ketoamine linkage with thiobarbituric acid after conversion to 5-hydroxymethylfurfural. In 4 of the 5 patients studied, glucosylation values exceeded the mean +2 S.D. of the controls; in the fifth subject glucosylation was in the high normal range. No correlation between the severity of diabetes and hexose content of GBMC was noted, however. In further studies, enzymatic glycosylation of GBMC was assayed after alkaline hydrolysis by separation of glucosylgalactosyl-O-hydroxylysine, galactosyl-O-hydroxylysine, and unsubstituted hydroxylysine in an amino acid analyzer. No differences in the relative contents of hydroxylysine-O-glycosides were evident between diabetic and control GBMC. The results suggest that non-enzymatic glucosylation, but not glycosylation catalyzed by collagen glucosyl and galactosyl transferases, is increased in diabetes. The increased carbohydrate content of collagen may lead to decreased turnover and/or excessive accumulations of basement membrane collagen thus contributing to the vascular complications of diabetes.
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PMID:Glycosylation of human glomerular basement membrane collagen: increased content of hexose in ketoamine linkage and unaltered hydroxylysine-O-glycosides in patients with diabetes. 621 60

We evaluated the possible role of islet glucokinase in controlling the rate of islet glucose metabolism, and thereby the rate of glucose-induced insulin release. The activities of glucokinase, hexokinase, P-fructokinase, and glyceraldehyde-P dehydrogenase were quantitated in sonicated or isotonically homogenized islet preparations using pyridine nucleotide-dependent fluorometric assays. In sonicates, about 1/4 of the islet glucose phosphorylating activity was due to an enzyme with kinetic properties similar to glucokinase; 3/4 of the activity was due to hexokinase. The procedure for determining islet glucokinase activity was improved by centrifuging isotonic islet homogenates at 12,000 x g. The supernatant fraction was enriched for glucokinase. About 1/2 of the glucose phosphorylating activity in this fraction was due to glucokinase and 1/2 was due to hexokinase. The glucokinase activity in islet homogenates was !23 of the activity of hexokinase, 1/40 of the activity of P-fructokinase, and 1/400 of the activity of glyceraldehyde-P dehydrogenase. Detailed concentration dependency curves of glucose and mannose utilization were also obtained with intact isolated pancreatic rat islets. Glucose and mannose usage in islets was governed by two superimposed hyperbolic systems differing in Km and Vmax. A high Km system (Km for glucose 11 mM and for mannose 21 mM) predominated. A low Km system (Km for glucose 215 and for mannose 530 microM) contributed about 15% to the total activity. The available data with intact islets could be rationalized by the existence of two distinct hexose phosphorylating enzymes with differing capacities and kinetic properties. These enzymes, tentatively identified as glucokinase and hexokinase, could coexist in the same cell or could be distributed among different cell types. The possible physiologic significance of these results is discussed, emphasizing the idea of dual control of glycolysis and insulin release by glucokinase and hexokinase. An earlier proposal that glucokinase serves as glucoreceptor of beta-cells [J. Biol. Chem. 243:2730 (1968)] is greatly strengthened by the present studies.
Diabetes 1981 Nov
PMID:Regulation of glucose metabolism in pancreatic islets. 627 17

Six normal dogs were made galactosemic by feeding a 30% D-galactose diet, and were followed up to 5 yr. For comparison, 10 normal dogs and 10 alloxan-diabetic dogs were concurrently fed the diet less the galactose supplement. Retinopathy occurred in each of four dogs glactosemic 3 or more yr, and was absent at lesser durations of galactosemia, and from normal dogs not given the galactose supplement. The retinopathy was marked by saccular capillary aneurysms, hemorrhages, nonperfused or acellular vessels, tortuous hypertrophic capillaries, loss of capillary pericytes, and other lesions typical of diabetic patients and alloxan-diabetic dogs. In galactose-fed dogs, blood galactose varied between 0 (fasted) and 250 mg/dl (postprandial), and glycosylated hemoglobin levels became supranormal. In contrast to diabetic dogs, blood levels of glucose, free fatty acids, and branched-chain amino acids were not elevated in the galactosemic dogs, and their serum insulin seemed normal. The results suggest that the level of blood hexose is itself an important determinant of retinopathy.
Diabetes 1984 Jan
PMID:Experimental galactosemia produces diabetic-like retinopathy. 636 Jul 71

Control of blood sugar involves the complex interaction of the pancreatic glucose-sensing beta-cells with the liver, which serves as the primary site of glucose disposal after a meal. Glucokinase occupies an important role in controlling glucose phosphorylation and metabolism both in the liver and in pancreatic islets. In the beta-cells, glucokinase functions as pacemaker of glycolysis at physiological glucose levels. It determines the unique characteristics of islet hexose usage, that is, the rate, affinity, cooperativity, and anomeric discrimination of glucose metabolism. Because glycolysis controls hexose-induced insulin release, glucokinase is considered the best-qualified candidate for the elusive glucose sensor of beta-cells. A deficiency of glucokinase would disturb glucose homeostasis. Decreased islet glucokinase would diminish islet glycolysis and would result in a higher set point of beta-cells for glucose-induced insulin release. Decreased liver glucokinase would cause less efficient hepatic glucose disposal. Human maturity-onset diabetes (type II diabetes) has these characteristics. It is thus conceivable that certain forms of type II diabetes are due to a glucokinase deficiency.
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PMID:New perspectives on pancreatic islet glucokinase. 636 28

Diabetes mellitus not infrequently coexists with hypo- and hyperthyroidism. Hyperthyroidism aggravates glucose intolerance. A review of this phenomenon reveals multiple mechanisms, which include increased hexose intestinal absorption, decreased responsiveness to insulin, and increased glucose production. Conflicting results are obtained when circulating insulin level is measured in thyrotoxicosis. The role of glucagon and alpha-cell sensitivity is unclear. Diabetes mellitus influences the assessment of thyrotoxicosis by falsely decreasing the blood levels of thyroxine (T4) and triiodothyronine (T3) during severely uncontrolled hyperglycemia. Hypothyroidism is found in about 3% of patients with insulin-dependent diabetes mellitus (IDDM). Moreover, 13-20% of IDDM patients have elevated blood thyrotropin levels and anti-thyroid antibodies. Hypothyroidism per se seems to ameliorate hyperglycemia. A subtype of IDDM shares similar immunogenetic features with familial autoimmune thyroiditis. Studies of IDDM probands who show a high prevalence of circulating thyroid antibodies reveal the presence of such antibodies in their first-degree relatives. Circulating islet-cell antibodies, detected in a majority of IDDM patients at the onset of their disease, tend to persist only in those patients with coexistent polyendocrine autoimmune disease, including thyroiditis. Similar human leukocyte antigen (HLA) locus types are associated with thyroiditis and IDDM, namely HLA-Dr3 and -Dr4.
Diabetes Care
PMID:Diabetes mellitus and thyroid disease. 640 Jul 13

Pieces of rat epididymal fat tissue were maintained in a biochemically defined medium for 20 to 44 hours in either the absence or presence of a sulfonylurea at levels known to be effective in humans. Prolonged exposure of adipocytes to sulfonylureas did not influence the number of insulin receptors or their affinity to insulin or the ability of insulin to induce receptor loss (down-regulation). Also, the sulfonylureas did not influence the basal uptake of the D-glucose analogs 2-deoxyglucose and 3-O-methylglucose. However, exposure to these drugs resulted in a potentiation of the stimulatory effects of insulin on hexose transport at submaximal and maximally effective concentrations of insulin. The average potentiation was approximately 30%. In addition, sulfonylureas enhanced stimulation of hexose uptake by the insulin mimickers, hydrogen peroxide and vitamin K5. These oxidants are known to manifest insulin-like actions subsequent to insulin binding. Under conditions in which glucose transport was rate limiting, the conversion of glucose to carbon dioxide and the total lipids mirrored the findings of hexose uptake. However, at a glucose concentration of 50 mM, at which hexose transport is no longer rate limiting, sulfonylureas did not potentiate metabolism in th absence or presence of insulin. These results may help to explain the hypoglycemic action of the drug in view of the recent finding that a postreceptor deficit is present in noninsulin-dependent diabetes mellitus.
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PMID:Extrapancreatic effects of sulfonylureas. Potentiation of insulin action through post-binding mechanisms. 640 22

Modifications of plasma lipoprotein structure and function resulting from in vivo post-translational nonenzymatic glycosylation may play a role in the premature atherosclerosis of patients with diabetes mellitus. This report describes the generation and characterization of six unique murine monoclonal antibodies that bind glucosylated human plasma lipoproteins, but do not react with normal plasma lipoproteins. This was accomplished by immunizing mice with homologous glucosylated low density lipoprotein. In competitive inhibition radioimmunoassays, the dominant epitope recognized by these antibodies on glucosylated low density lipoprotein was identified as glucitollysine, the reduced hexose alcohol form of glucose conjugated to the epsilon amino group of lysine. Each of these antibodies was capable of identifying glucitollysine epitopes on all reduced glucosylated proteins studied, including high density lipoprotein, albumin, hemoglobin, and transferrin. These antibodies were also capable of identifying and quantitating glucitollysine residues on the total plasma proteins and isolated lipoproteins of normal and diabetic individuals after reduction of the proteins with NaBH4. Preliminary data suggest that diabetic total plasma proteins and isolated lipoproteins contain at least threefold more immunochemically detectable glucitollysine residues than nondiabetic plasma proteins and lipoproteins. The technique described in this report should allow production of region-specific antibodies to any immunogenic modification of a protein.
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PMID:A novel method for generating region-specific monoclonal antibodies to modified proteins. Application to the identification of human glucosylated low density lipoproteins. 641 10

For a better understanding of the processes leading to diabetic microangiopathy, type IV collagen from kidneys of patients with long-term diabetes was compared with the collagen from kidneys of sex- and age-matched controls. Type IV collagen from diabetic kidneys revealed no abnormalities in amino acid composition, hydroxylation of proline and lysine, enzymatic glycosylation of hydroxylysine, and immunological reactivity with several monoclonal and polyclonal, anti-type IV collagen antibodies. However, ketoamine-linked hexose, resulting from the nonenzymatic condensation of glucose with lysyl or hydroxylysyl residues, was 1.7-fold higher in diabetic type IV collagen. The stoichiometry of this modification was estimated to be 1-2 residues of hexose per triple helical molecule (Mr 380,000). This small amount of ketoamine-linked hexose might hardly have an effect on the function and turnover of type IV collagen, unless it is bound to a crucial site along the collagen molecule. The nonenzymatic glycosylation of collagen might therefore be a mere consequence of the metabolic disturbances, rather than the primary cause for the late complications of diabetes mellitus.
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PMID:Nonenzymatic glycosylation of basement membrane collagen in diabetes mellitus. 647 68


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