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

Hyperglycemia (experimental diabetes) was induced in adult male rats by destruction of the pancreatic beta cells with a single intravenous injection of streptozotocin (STZ). Testes from diabetic, from insulin-treated diabetic, and from sham-injected normal rats were fxed by vascular perfusion. The fine structure of Leydig cells was examined at two, three, and four weeks after the STZ injection in the untreated diabetic animals, and at four weeks in the controls and insulin-treated diabetic rats. A number of morphological changes was observed in Leydig cells of untreated diabetic animals. Most obvious of these was an accumulation of lipid droplets, not normally present in Leydig cells in adults of this species. Smooth endoplasmic reticulum (SER) was markedly reduced in Leydig cells of the hyperglycemic rats. Several types of intracellular bodies were seen exclusively in Leydig cells of the untreated diabetic animals. Many resembled secondary lysosomes or dense bodies, while others appeared to be autophagic vacuoles. In addition, a small, granule-containing lamellar structure was seen either within a typical dense body or free in the cytoplasm. Myelin-like structures were commonly observed within the cytoplasm of the Leydig cell or within mitochondria. The appearance of the mitochondria in diabetic rats was otherwise normal. The extracellular spaces surrounding Leydig cells from untreated hyperglycemic rats also contained large accumulations of myelin-like material. These structural changes appear to be direct consequences of the diabetic state of the animals, since the ultrastructure of insulin-treated diabetic rats did not differ from that of the controls. These findings may reflect an alteration or breakdown of Leydig cell components normally involved in the synthesis of androgen, and correlate with previous reports of lowered circulating levels of testosterone in diabetic rats.
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PMID:Ultrastructural changes in Leydig cells of streptozotocin-induced diabetic rats. 22 65

We have presented and reviewed evidence for the heterogeneous nature of diabetes mellitus in terms of genetics, environmental factors, insulin responses to glucose and vascular disease. We have reviewed evidence for heterogeneity between juvenile-onset diabetes (JOD) and maturity-onset diabetes (MOD) and maturity-onset diabetes of young (MODY) and for heterogeneity within groups of JOD and MOD and MODY patients. Although much remains to be learned, a beginning has been made and suggests that primary diabetes mellitus is not a single specific disease but a syndrome comprised of a variety of diseases all characterized by hyperglycemia and tissue changes that result from heterogeneous etiologic and pathogenetic factors. Future classifications of primary diabetes mellitus will undoubtedly be lengthy, as are for other diseases and syndromes also caused by a variety of etiologic and pathogenetic mechanisms.
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PMID:Clinical and etiological heterogeneity of idiopathic diabetes mellitus. The banting memorial lecture. 22 48

Stupor in patients with nonketotic hyperglycemia has been ascribed to hyperosmolarity, but the cause of depressed consciousness in patients with ketoacidosis has been puzzling. In this study, blood pH, serum glucose and sodium concentrations, and serum osmolality were measured in eighty-five consecutive episodes of diabetic ketoacidosis and forty-seven of nonketotic hyperglycemia. In the acidotic patients, as in those with nonketotic hyperglycemia, stupor closely paralleled hyperosmolarity and not the severity of acidemia. Indeed, the mean elevations of serum osmolarity were almost the same in the ketotic and in the nonketotic patients who were deeply obtunded. It seems likely that depression of consciousness in patients with severely uncontrolled diabetes mellitus, if not due to a nonmetabolic disorder, such as acute stroke, is attributable to hyperosmolarity, whether or not ketoacidosis is present.
Diabetes 1975 Jun
PMID:Hyperosmolar nature of diabetic coma. 23 99

This brief review of the sorbitol pathway has attempted to present our current knowledge of this accessory pathway of glucose metabolism in the development of some diabetic complications. Clearly hyperglycemia in the diabetic patient is an important factor controlling the activity of the sorbitol pathway. Hyperglycemia in both diabetic patients and experimental animals results in significant accumulations of the products of this pathway in some tissues, and these diabetic manifestations. The development of inhibitors of the aldose reductase enzyme affords new means for preventing and treating some of these complications. Nevertheless, we are still hampered by the lack of knowledge of the normal role of this pathway in tissue metabolism. Many technical problems still exist concerning sensitive and specific assays for the products of the sorbitol pathway in tissue studies, as well as with valid techniques for the measuremtn of the activity of this pathway in clinical situations. It is hoped that clinical studies with aldose reductase inhibitors in the future will further clarify the importance of this accesory pathway of glucose metabolism in diabetes.
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PMID:Hyperglycemia, polyol metabolism, and complications of diabetes mellitus. 23 58

Hemoglobin A1c concentration (HbA1c) was compared to the plasma glucose responses at 1 and 2 h of an oral glucose tolerance test (OGTT) in 63 subjects preselected because of postprandial hyperglycemia. HbA1c concentrations were correlated with 1- and 2-hour plasma glucose responses during the OGTT (r = 0.776 and 0.8602, respectively). The OGTT responses were diabetic-like in 21, indeterminate in 15, and normal in 27 subjects. HbA1c values were within normal limits in all subjects who had a normal or indeterminate OGTT response and in 10 out of 21 with a diabetic OGTT. The 2-h OGTT response among the 10 diabetic responders with normal HbA1c was 200 +/- 31 mg/100 ml (mean +/- SD), while that of the 11 diabetic responders with elevated HbA1c was 352 +/- 122 mg/100 ml. All subjects with an elevated HbA1c had a 2-h plasma glucose above 228 mg/100 ml, whereas only 7% of subjects with a normal HbA1c had a 2-h glucose above this value. It is concluded that only about half of the patients currently diagnosed as having mild or chemical diabetes by OGTT have elevated HbA1c and that an elevated HbA1c is usually associated with 2-h OGTT levels above 228 mg/100 mg.
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PMID:Hemoglobin A1c levels in a diabetes detection program. 26 11

Diabetes is associated with a fluctuating impairment in oxygen transport of the erythrocytes. This impairment is correlated with hyperglycemia by the formation of glycosylated hemoglobin (HbAIC) and with inhibitory factors of glycolysis i.e. hypophosphatemia and acidosis which lower the concentration of red cell 2,3-diphosphoglycerate. Diabetic angiopathy may be the ultimate result of innumerable microvascular responses to discrete hypoxic injuries associated with increased plasma permeation through the vessel walls. It is shown that two additional risk factors for atherosclerosis--smoking and hypertriglyceridemia may also lead to arterial wall hypoxia by changing the position of the oxyhemoglobin dissociation curve.
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PMID:Diabetic vascular disease. The importance of insulin deficiency, hyperglycemia and hypophosphatemia on red cell oxygen unloading. 27 65

Use of an ion exchange chromatographic method and a colorimetric method with thiobarbituric acid showed that levels of nonenzymatically glucosylated serum albumin were increased in patients with poorly controlled diabetes mellitus compared to controls. The two methods correlated well (r = 0.99) and clearly discriminated between normal and poorly controlled diabetic populations. The levels of glycosylated hemoglobin were also measured in both populations. Several patients apparently in good control based on glycosylated hemoglobin measurements were found to have increased levels of glycosylated albumin. Because albumin has a shorter circulating half-life than does the human erythrocyte, the plasma concentration of glucosylated albumin should be expected to reflect short-term control of hyperglycemia in diabetes. The studies reported here suggest that the level of glucosylated albumin may indeed be a sensitive indicator of moderate hyperglycemia and of early glucose intolerance.
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PMID:Enhanced nonenzymatic glucosylation of human serum albumin in diabetes mellitus. 29 61

These experiments have been designed to study the influence of alanine infusion of glucose dynamics in the dog and to further elucidate the role of pancreatic hormones in the interaction of alanine with glucose homeostasis. The primed constant infusion of glucose-2-t was used in order to quantitate the rates of glucose production by the liver (Ra) and glucose utilization (Rd). In a first group of experiments, the intravenous infusion of alanine at the rate of 2 mg./kg./min. produced a moderate enhancement of plasma insulin (IRI), while pancreatic glucagon (IRG) increased more consistently. This different pattern of IRI and IRG response caused the insulin/glucagon molar ratio to decline progressibely throughout the experiment. Both rates of glucose turnover increased significantly during alanine infusion. Since Ra rose more rapidly thanRd did initially, hyperglycemia developed. Later, glucose production slowly decreased and, in spite of the sustained hyperglucagonemia, reached levels very close to the baseline in the second part of the experiment. A significant direct correlation between Ra and IRG was found, while the changes in Ra correlated inversely with those in I/G molar ratio. In a second group of experiments, alanine was infused at the same dose together with 0.4 microng./kg./min. of cyclic somatostatin. In the first part of the infusion, IRG fell more than IRI did, so that I/G ratio increased. Later, IRI levels maintained at low values while IRG returned slowly to the baseline and consequently I/G ratio significantly decreased. Glucose production fell rapidly soon after the beginning of the infusion, and therefore hypoglycemia developed. Later, Ra increased progressively to levels above baseline and plasma glucose returned to the preinfusion levels. As in the the first group of experiments, a significant direct correlation between Ra and IRG and an inverse correlation between the changes in Ra and I/G ratio were observed. These experiments demonstrate that alanine infusion produces an acceleration of glucose turnover and that a clear interrelationship between the release of glucose by the liver and the mobilization of pancreatic hormones exists. Finally, the experiments with somatostatin indicate that hyperglucagonemia is one of the mechanisms underlying the stimulatory effect of alanine on glucose production.
Diabetes 1977 Apr
PMID:Studies on the mechanism underlying the influence of alanine infusion on glucose dynamics in the dog. 30 Mar 41

Cell-mediated immunity was evaluated in patients with diabetes mellitus by delayed hypersensitivity skin tests and in vitro lymphocyte transformations. Only 44% of diabetic patients had skin test reactivity to Candida antigen, compared with 88% of normal controls (P < 0.001). Insulin-dependent diabetic (IDD) patients had abnormally low lymphocyte transformation responses to phytohemagglutinin, concanavalin A, and streptokinase-streptodornase (P < 0.05). This defect was not corrected by culturing the cells in nondiabetic plasma. IDD patients with persistent hyperglycemia (fasting serum glucose level, >200 mg/dl) had lower levels of transformation than did IDD patients with fasting serum glucose levels less than 150 mg/dl. Lymphocytes from two IDD patients with poor lymphocyte transformation responses had marked improvement in response to phytohemagglutinin when the lymphocytes were cultured after a preincubation period designed to deplete cultures of suppressor activity. Seven IDD patients were studied serially over 12 months. Lymphocyte transformation responses in four of these patients improved coincidentally with a change in the level of fasting hyperglycemia from >200 to <150 mg/dl. The other three IDD patients with consistent fasting serum glucose levels of >200 mg/dl had poor lymphocyte transformation responses. Diabetic patients have demonstrable defects in lymphocyte function which improved in a small number of patients with reduction in the level of fasting hyperglycemia.
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PMID:Cell-mediated immunity in diabetes mellitus. 30 93

1. Six weeks after the injection of streptozotocin at 125 mg/kg i.p. in the AV line nondiabetic Chinese hamsters, the animals showed hyperglycemia, increased kidney, pancreas and stomach weights and stomach glucagon contents and depletion of insulin and glucagon in the pancreas. 2. Plasma beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase were elevated; whereas alpha-D-glucosidase was decreased and alpha-D-galactosidase remained unchanged in the plasma. 3. In the kidney, streptozotocin-diabetes led to depression of alpha-D-mannosidase, beta-D-fucosidase and N-acetyl-beta-D-glucosaminidase activities in both 12,000 g supernatant and precipitate fractions, decreases in alpha-D-glucosidase in the supernatant only and no change in alpha-L-fucosidase, alpha-D-galactosidase, beta-D-galactosidase and beta-D-glucuronidase. 4. In the liver, significant increases in N-acetyl-beta-D-glucosaminidase, alpha-D-galactosidase, beta-D-galactosidase, beta-D-fucosidase, beta-D-glucosidase and alpha-D-mannosidase were found in either the supernatant or the precipitate fraction of the diabetic animals. The data indicate diabetes-dependent tissue-specific changes in glycohydrolases in the Chinese hamster.
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PMID:Alterations in glycohydrolase activities in streptozotocin-diabetic Chinese hamsters (Cricetulus griseus). 31 16


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