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

The effect of diabetes and insulin on the activities of both prolyl hydroxylase (trivial name; proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) and lysyl hydroxylase (trivial name; lysine,2-oxoglutarate dioxygenase, EC 1.14.11.4) in isolated rat renal glomeruli was determined. Three groups of experimental animals were used: age-matched controls, streptozotocin-diabetic, and insulin-treated streptozotocin-diabetic. Using 14C-labeled lysine or proline hydroxylase substrate prepared from chick embryo tibiae, glomerular 17 000 X g supernatant enzyme was incubated in a complete hydroxylating system for 60 and 120 min Lysyl hydroxylase activity was significantly increased in diabetic preparations, but prolyl hydroxylase activity did not differ from control. Administration of insulin to streptozotocin-injected animals completely restored glomerular lysyl hydroxylase to normal levels. The results suggest that the specific elevation of lysyl hydroxylase relates to the biochemical changes contributory to diabetic nephropathy, and that insulin may reverse this process.
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PMID:Effect of diabetes and insulin on rat renal glomerular protocollagen hydroxylase activities. 18 35

The effect of diabetes on the metabolism of the renal glomerular basement membrane has been studied in the rat with the aid of injected tracer doses of tritiated proline. At various times after administration of the labeled amino acid, the specific radioactivities of the proline and hydroxyproline of the basement membranes from alloxan diabetic rats were determined and compared with those of age-matched normal rats. In both normal and diabetic animals the incorporation of radioactivity into the basement membrane was slow and, after a maximum was reached, an extended period of almost constant specific activity of proline and hydroxyproline was observed. The diabetic basement membrane, however, differed from the normal by attaining specific activities of the amino acids which were about twice as high as normal (P less than 0.001 at 42 h after injection of radioisotope). Although the proline concentration of serum and renal cortical fluid was the same in normal and diabetic rats, there were substantial differences in the specific activity of this precursor amino acid in these pools that had to be taken into account to compare the two types of animals. The results of the present study are consistent with an accelerated rate of glomerular basement membrane polypeptide synthesis and proline hydroxylation in diabetes.
Diabetes 1979 Feb
PMID:Glomerular basement membrane metabolism in the diabetic rat. In vivo studies. 42 69

The content of the following 10 amino acids was investigated by means of a microbiological method (with the use of auxotrophic E. coli mutants) in 23 patients with diabetes mellitus with fatty infiltration of the liver and in 27 patients without it: histidine, proline, methionine, cystine, tryptophane, leucine, arginine, tyrosine, lysine, and phenylalanine. Results of study of the amino acid balance were compared with the morphological changes in the liver (the material was obtained by biopsy). All the diabetic patients displayed an increase in the proline, tryptophane, tyrosine, leucine, and cystine content, and a reduction of phenylalanine and lysine level. Fatty hepatocyte infiltration was also accompanied by a significant elevation of methionine and a reduction of arginine content. A tendency to normalization of leucine and lysine only was seen after the treatment of diabetic patients with fatty hepatocyte infiltration; diabetic patients without any fatty infiltration showed normalization in the tyrosine, lysine content and a tendency to the normalization of the cystine, tryptophane level, but no change in the methionine content.
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PMID:[Characteristics of the amino acid spectrum of blood serum in diabetes mellitus]. 88 34

Wound healing as a model for diabetic angiopathy has been studied by light and electron microscopy. Biochemical studies of the rate of incorporation of 3H-proline and 3H-thymidine into collagen and DNA, respectively, have confirmed the morphologic observations. In both the normal and the diabetic, there was a marked decrease in the rate of collagen and DNA synthesis, suggesting that most of the cells in the biopsies were stunned by the injury and ceased DNA replication during the initial phase. In control mice this decrease was followed by a modest but significant burst of DNA replication, which peaked at two hours and by the fourth hour had returned to the one-hour level. In the diabetic this burst of DNA replication was absent and no capillary morphogenesis was seen at two, four, and eight hours. At 16 hours, there were only a few abnormal nascent vessels observed in the diabetic and antiserum-treated mice. The peak in the rate of collagen synthesis at four hours correlated well with the condensation of collagen at the wound margin and the fibroblast rough-endoplasmic-reticulum (RER) proliferation. In the diabetic mice, there was a significantly attenuated rate of collagen synthesis for the entire 16-hour period. The lack of DNA replication, capillary morphogenesis, fibroblast RER proliferation, and decreased collagen synthesis in the diabetic mouse can be considered interrelated and significant factors in the diabetic's impaired response to cellular injury. In view of the increased frequency and severity of injury to the circulation of the diabetic and the impaired response to repair such injury, it is likely that wound healing is a promising model for diabetic angiopathy.
Diabetes 1976
PMID:Wound healing: a model for the study of diabetic angiopathy. 97 88

Renal substrate exchange was examined in five male patients with insulin-dependent diabetes mellitus of several years' duration. Insulin was withheld for twenty-four hours prior to the study. A renal vein was catheterized from the femoral vein, and PHA-clearance was employed for the determination of effective renal blood flow. None of the patients was in ketoacidosis, but all were moderately hyperglycemic in the fasting states (16.8 +/- 1.5 mmol/L.) (225-384 mg./100 ml.). Nevertheless, no net release of glucose from the kidney was detectable. Instead, there was a significant net renal uptake of glucose (320 +/- 80 mumol/min.). In addition, there was a significant net uptake of glycerol and a net release of pyruvate. Renal amino acid exchange was similar to that reported for healthy subjects: glutamine, glycine, proline, and citrulline were taken up and serine, alanine, cystine, tyrosine, and threonine were released by the kidney. It is concluded that (a) in nonketoacidotic diabetics there is no net production of glucose by the kidney; (b) renal amino acid exchange in diabetics is similar to that of healthy individuals; and (c) the kidney is not an important gluconeogenic organ in human diabetes.
Diabetes 1975 Aug
PMID:Renal substrate exchange in human diabetes mellitus. 115 36

Combined biochemical and ultrastructural study of conjunctival biopsies of 27 normal subjects and 45 diabetics (40 to 60 years old) was made. The "in vitro" incorporation of 14C-glucosamine and 3H-proline in freshly excised conjunctival biopsies was studied. The alterations of the capillary basement membrane of the conjunctiva were studied by electron microscopy. The following results were obtained: 1) A decrease of the specific activity of 14C-glucosmaine incorporation was found in fractions of diabetic conjunctiva. 2) In diabetic conjunctiva the percentages of 3H-proline incorporation in polymeric collagen containing fraction and structural glycoproteins containing fraction were significantly increased with a parallel decrease of 3H-proline incorporation in "crude soluble collagen" fraction expressed as a percentage of total incorporation. 3) Significant thickening of capillary basement membrane was observed with the appearance of collagen-like fibrils within the basement membrane in diabetic conjunctiva. Such fibrils were not seen in normal basement membranes. A relation between the extent of basement membrane thickening and the appearance of collagen-like fibrils is suggested. 4) The higher percentage of incorporation of 3H-proline in polymeric collagen may be related to the appearance of collagen fibrils in thickened basement membranes of the diabetic conjunctival capillaries. 5) These results suggest an abnormal regulation of the relative rate of biosynthesis and/or excretion of intercellular matrix macromolecules (collagen, structural glycoproteins) as part of the metabolic disorders characterising diabetes.
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PMID:Biochemical and ultrastructural study of human diabetic conjunctiva. 126 6

Muscle contraction in vitro increases glucose uptake (GU), independent of insulin, but in vivo, the exercise-induced increase in GU is impaired in insulin-deficient diabetic dogs. We wished to determine whether, in vivo, suppression of the free fatty acid (FFA)-glucose cycle with methylpalmoxirate (MP, inhibitor of FFA oxidation) alone or combined with propranolol (PRO, beta-blocker) could improve GU during exercise in the absence of insulin. We performed four groups of exercise experiments (6 km/h, 10% slope) in depancreatized insulin-deprived dogs: 1) control (n = 6); 2) MP treated (5 oral doses of 10 mg/kg, twice daily, n = 6); 3) treated with MP+octanoate (OCT; oxidation unaffected by MP, 27 mumol.kg-1.min-1 iv during exercise; n = 5); and 4) MP+PRO treated (5 micrograms.kg-1.min-1 iv during exercise, n = 6). MP abolished ketosis (inhibition of hepatic FFA oxidation), decreased basal glucose production (GP), and increased metabolic clearance of glucose (MCR). During exercise, MP attenuated the increment in GP (P < 0.01), which was reversed by OCT. MP did not affect the exercise-induced increase in GU and MCR. With MP+PRO, FFAs decreased and lactate did not rise during exercise. GP was not further suppressed, but GU and MCR were increased (P < 0.01) to 89 and 31% of normal, respectively. In insulin-deprived depancreatized dogs, glucose cycling was increased to a greater extent than GP, as in type II diabetes. By the end of exercise, glucose cycling increased (P < 0.05), but to a similar extent as GP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of FFA-glucose cycle in glucoregulation during exercise in total absence of insulin. 141 84

The effect of insulin on the transport of proline has been studied in cultured fibroblasts from normal individuals, non-insulin-dependent diabetic patients, and patients with Werner syndrome. In fibroblasts from normal individuals and those with diabetes mellitus, incubation with 10(-7) M insulin resulted in more than a twofold increase in the transport rate after about 14 h incubation. In contrast, fibroblasts from patients with Werner syndrome had a markedly attenuated response to insulin, suggesting a defect in insulin action on the transport of this amino acid in Werner syndrome.
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PMID:Effect of insulin on the proline transport activity in cultured fibroblasts from patients with Werner syndrome. 141 49

Streptozotocin-induced, insulin-deficient diabetic adult rats were daily administrated either minocycline or a chemically-modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week time period; untreated diabetic and non-diabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The upper and lower mandibles of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by fibroblasts in the periodontal ligament (PDL) of molars. In the non-diabetic controls, at 20 min after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of PDL fibroblasts. At the 4-h time period, most of the label was present over the collagen fibers around these cells. In contrast, PDL fibroblasts in the untreated diabetic rats showed marked abnormalities ultrastructurally and minimal uptake (20 min) and secretion (4 h) of labeled proline. At both time periods, in both minocycline- and CMT-treated diabetic rats, fibroblasts were structurally more normal and the radioprecursor was localized in the fibroblasts and the PDL matrix in a pattern similar to that seen in the control rats. These results suggest that the diabetes-induced structural abnormalities and suppression of synthesis and secretion of protein (presumably collagen and its precursor) by PDL fibroblasts can be restored to near-normal by administration of a tetracycline and that this effect is mediated by a non-antimicrobial property of this family of antibiotics.
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PMID:Tetracycline administration increases protein (presumably procollagen) synthesis and secretion in periodontal ligament fibroblasts of streptozotocin-induced diabetic rats. 146 May 49

Streptozotocin-induced, insulin-deficient diabetic rats were administrated either minocycline (MC) or a chemically modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week period; untreated diabetic and nondiabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The parietal bones of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by osteoblasts. At 20 minutes after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of the osteoblasts in the periosteal surface of the control rats. At the 4-hour time period, most of the label was present over the collagen fibers of the osteoid. In contrast, the flattened bone-lining cells in the untreated diabetic rats showed minimal uptake (20 minutes) and secretion (4 hours) of labeled proline. In both MC and CMT-treated diabetic rats, the radioprecursor was localized in the osteoblasts and osteoid matrix in a pattern similar to that seen in the control rats at both 20 minutes and 4 hours after isotope injection. Labeling of the osteoid by the radioprecursor was greater as a result of CMT treatment than during minocycline treatment. These results suggest that the diabetes-induced suppression of synthesis and secretion of protein (presumably collagen and its precursor) by osteoblasts can be restored to near-normal levels by administration of tetracycline(s) and that this effect is mediated by a non-antimicrobial property of these antibiotics.
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PMID:Tetracycline administration increases collagen synthesis in osteoblasts of streptozotocin-induced diabetic rats: a quantitative autoradiographic study. 153 8


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