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

Many of the chronic complications of diabetes mellitus involve defects in the connective tissue such as poor wound healing, diminished bone formation, and decreased linear growth. Because collagen is the major protein component of these connective tissues, we examined collagen production in diabetic rats as a probe of this generalized defect in connective tissue metabolism. Doses of streptozocin ranging from 35 to 300 mg/kg were used to induce diabetes of graded metabolic severity in rats. Parietal bone or articular cartilage was removed and incubated at 37 degrees C with 5 microCi L-[5-3H]proline for 2 h, and collagen and noncollagen protein production were quantitated after separation with purified bacterial collagenase. Within 2 wk after induction of diabetes, collagen production was significantly reduced in bone and cartilage from diabetic rats to 52% (P less than .01) and 51% (P less than .01) of control (buffer-injected) levels, respectively. In contrast, noncollagen protein production in bone and cartilage from diabetic animals was no different from in tissue from control rats. The correlation between collagen relative to total protein production (relative rate) and the degree of hyperglycemia was highly significant for both bone (r = -.77, P less than .001) and cartilage (r = -.87, P less than .001). Other factors found to correlate with altered collagen production were the duration of diabetes and the amount of weight loss. Thus, diabetes is associated with a marked decrease in collagen production, which was seen early after induction of diabetes and was specific when compared with noncollagen protein production. Cumulative effects of these marked changes in collagen production may contribute to the chronic connective tissue complications in diabetes.
Diabetes 1988 Apr
PMID:Decreased collagen production in diabetic rats. 337 83

This is the first study concerning the extent to which relative collagen production (RCP) in rat periodontal tissues is affected by diabetes. Determination of RCP, rather than individual production rates for collagen or for non-collagen protein, was deemed necessary because saturation of all proline pools in tissues of diabetics (and non-diabetic controls) was not achieved. Such non-saturation occurred despite the injection of a pool-expanding dose of proline (400-1150 mg/rat), non-saturation indicated by the lesser specific radioactivity (S.R.) of free-[3H]proline in tissues than that of the injected solution. RCP was decreased in five periodontal tissues (incisor and molar gingiva, incisor and molar periodontal ligament, antemolar palatal mucosa) and in skin. Diabetes-decreased RCP seems to result from decreased collagen synthesis and increased intracellular degradation, although some evidence is presented for increased extracellular degradation of recently secreted collagen.
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PMID:Streptozotocin-induced diabetes and the rat periodontium: decreased relative collagen production. 339 6

1. The effect of streptozotocin-induced diabetes (7 day duration) in rats on D-glucose uptake in vivo, the unidirectional uptake of D-glucose and L-proline in vitro, the passive uptake of L-glucose in vitro and the potential difference across the brush-border membrane has been studied. 2. Diabetes resulted in an increased carrier-mediated glucose uptake both in vivo and in vitro and a stimulation of L-proline uptake at a concentration of the amino acid (0.025 mM) at which uptake was largely Na+ dependent. Diabetes was without effect on uptake using a proline concentration of 50 mM at which transport was predominantly Na+ independent. 3. A marked hyperpolarization of the brush-border membrane and an enhanced passive glucose uptake were also evident during diabetes. 4. We conclude that the stimulation of glucose uptake in vivo in diabetic intestine involves events at the brush-border membrane. The mechanisms include an increased surface area for uptake and an enhanced transmembrane electrical gradient. The latter will have a major effect on the transport of other substrates when the uptake pathway is primarily Na+ dependent.
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PMID:Nutrient uptake by rat enterocytes during diabetes mellitus; evidence for an increased sodium electrochemical gradient. 341 16

The effects of maternal diabetes on the mandibles in the fetuses of dams given a normal (20% protein) diet vs those given a high protein (40% protein) diet were studied. On day 9, the controls, groups 1 and 3, were injected with citrate buffer and fed a 20% and 40% protein diet, respectively. Groups 2 and 4 were injected with 40 mg/kg B.W. of streptozotocin and pair-fed with groups 1 and 3 with a 20% and 40% protein diet, respectively. On day 22, fetuses were removed. Dissected mandibles were weighed and analyzed for DNA, protein, Ca and hydroxyproline contents. Some dams in each group were injected with either 45Ca or 14C proline to study 45Ca uptake and collagen synthesis. The body and mandibular weights of the fetuses from diabetic (D) dams were smaller than those of the non-diabetic (ND) group in both diets. The protein and hydroxyproline contents of the mandible in the D 20% group was less than the ND. Hydroxyproline content from the D 40% group was less than the ND. The Ca content in the D 40% group was less than the ND. The present study indicates that metabolism in the bone of fetuses whose D dams were fed a high protein diet is affected beneficially in some parameters but not in others.
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PMID:Effects of maternal dietary protein on the mandibular growth of fetuses from diabetic dams. 360 88

The effect of glucose on extracellular production of collagen and protein was studied in cultured human skin fibroblasts. Fibroblasts from 8 non-diabetics, 8 type 1 and 12 type 2 diabetic subjects were cultured. Incorporation of tritium labeled proline into medium collagen and protein was studied at glucose concentration 1-7 mg/ml (5.6-38.9 mM). A 75% increase in collagen production was noted by cells from type 1 diabetics at glucose concentration of 5 mg/ml, as compared to 1 mg/ml. A considerably lower although significant increase was also noted at this level by cells from non-diabetics. Glucose had no effect on collagen and minimal on protein production by cells from type 2 diabetic subjects. The results indicate an effect of glucose on extracellular matrix formation in diabetes mellitus which might be relevant for diabetic angiopathy.
Diabetes Res 1986 Feb
PMID:Influence of glucose on collagen and protein production in cultured human skin fibroblasts from diabetic and non-diabetic subjects. 369 83

To further define the pathogenesis of diabetic connective tissue lesions, collagen synthesis and degradation were measured in vivo in spontaneously diabetic db/db mice. A double isotopic labeling technique, in which 14C-labeled and 3H-labeled proline were injected into the same mouse 7 days apart, was applied. Collagen synthesis and degradation were assessed in skins, intestines, hearts, and kidneys. There were no changes in collagen metabolism in the intestines of the diabetic mice. In all other tissues, collagen degradation was accelerated. Collagen synthesis was decreased in skins, but increased in the hearts and kidneys of the diabetic mice. These tissue-specific changes in collagen metabolism resulted in a net loss of collagen in all tissues examined except intestines. The results of this study provide insight into the mechanisms leading to connective tissue defects occurring in diabetes mellitus.
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PMID:In vivo collagen metabolism in spontaneously diabetic (db/db) mice. 377 Jan 46

The canine gastric mucosa has previously been shown to contain considerable amounts of a polypeptide with the immunologic and physicochemical characteristics and biologic activity of glucagon (IRG3500). Using mucosal pieces that remained viable for at least 8 h, we have demonstrated that IRG3500 is synthesized in this extrapancreatic tissue. Gel filtration and electrophoresis of extracts of mucosal pieces incubated with 3H-tryptophan, 3H-leucine, or 35S-methionine revealed small amounts of labeled, newly synthesized gastric IRG3500. No labeling of gastric IRG3500 was observed when the mucosa was incubated with 3H-proline, an amino acid not found in glucagon, in the presence of cycloheximide, or in isolated rat hepatocytes. Small amounts of newly synthesized IRG3500 were specifically immunoprecipitated by C-terminally directed glucagon antiserum gamma globulins. The rate of gastric IRG3500 biosynthesis in vitro was apparently unchanged in mucosal pieces from pancreatectomized dogs and unaffected by increased glucose or glucose lack during incubations. Thus we have provided evidence that a hormone of the endocrine pancreas can be synthesized in extrapancreatic tissues.
Diabetes 1985 Jan
PMID:Biosynthesis of glucagon (IRG3500) in canine gastric mucosa. 388 May 48

Insulin-dependent diabetes mellitus (IDDM) induces plasma amino acid (AA) abnormalities, including low alanine and high branched-chain (BCAA). While insulin treatment restores plasma AA pattern, proline, methionine, valine, isoleucine, and total BCAA remain elevated in skeletal muscle intracellular water. This suggests that the restoration of plasma AA concentrations is not a satisfactory index of recovered AA metabolism in IDDM.
Diabetes 1985 Aug
PMID:Plasma and skeletal muscle free amino acids in type I, insulin-treated diabetic subjects. 389 23

Pancreatic islets contain large-quantities of thyrotropin-releasing hormone (TRH) and of its metabolite Histidyl-Proline diketopiperazine (Cyclo His-Pro). The effects of these two putative neurotransmitters on the pancreatic B-cell function have been evaluated in vitro, with islets of normal or dysthyroid mice. TRH and Cyclo His-Pro (10(-11)-10(-6) M) were without effect on insulin release induced by 10-20 mM glucose in islets of normal mice. They transiently accelerated the slow waves of membrane potential triggered in B cells by 10 mM glucose, but did not cause any sustained change in overall electrical activity, and did not affect the rate of 86Rb+ efflux from islet cells. They were also ineffective when insulin release was stimulated by leucine or arginine, or was potentiated by forskolin, an activator of the adenylate cyclase. Hyperthyroidism (induced by injections of thyroxine) caused a fall in islet insulin content, but augmented the 2 phases of glucose-induced release. On the other hand, hypothyroidism (induced by a low iodine diet and propylthiouracil) caused an increase in islet insulin content, but depressed the second phase of release. TRH did not affect either phase of insulin release by islets of hyperthyroid or hypothyroid mice. These results show that pancreatic B cells are not a target for TRH and Cyclo His-Pro.
Diabetes Res 1985 Mar
PMID:Thyrotropin-releasing hormone and insulin release: in vitro studies with islets of normal and dysthyroid mice. 393 Jan 25

To identify the mechanisms responsible for the paucity of recently synthesized collagen in connective tissues during diabetes, in vitro procollagen metabolism was studied in non-diabetic (control) and diabetic rats. Achilles tendons from the two groups were incubated for 1-8 h (35 degrees C) in medium containing [14C]proline and the radiolabeled collagen in the tissue, and that released into the media, were examined by SDS-polyacrylamide gel electrophoresis and fluorography. The bulk of the radiolabeled collagen in tendon from the diabetics was recovered as degradation products; these, but also procollagen and collagen components, were prominent in the control tissues. Moreover, the collagenous components synthesized by the diabetic rat tendons were more readily digested in vitro by trypsin than those produced by control tissues. We conclude that diabetes reduces collagen accretion in connective tissues in part due to increased intracellular degradation of procollagen.
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PMID:Diabetes stimulates procollagen degradation in rat tendon in vitro. 394 86


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